WorldWideScience

Sample records for significant phase advances

  1. Uranium chemistry: significant advances

    International Nuclear Information System (INIS)

    Mazzanti, M.

    2011-01-01

    The author reviews recent progress in uranium chemistry achieved in CEA laboratories. Like its neighbors in the Mendeleev chart uranium undergoes hydrolysis, oxidation and disproportionation reactions which make the chemistry of these species in water highly complex. The study of the chemistry of uranium in an anhydrous medium has led to correlate the structural and electronic differences observed in the interaction of uranium(III) and the lanthanides(III) with nitrogen or sulfur molecules and the effectiveness of these molecules in An(III)/Ln(III) separation via liquid-liquid extraction. Recent work on the redox reactivity of trivalent uranium U(III) in an organic medium with molecules such as water or an azide ion (N 3 - ) in stoichiometric quantities, led to extremely interesting uranium aggregates particular those involved in actinide migration in the environment or in aggregation problems in the fuel processing cycle. Another significant advance was the discovery of a compound containing the uranyl ion with a degree of oxidation (V) UO 2 + , obtained by oxidation of uranium(III). Recently chemists have succeeded in blocking the disproportionation reaction of uranyl(V) and in stabilizing polymetallic complexes of uranyl(V), opening the way to to a systematic study of the reactivity and the electronic and magnetic properties of uranyl(V) compounds. (A.C.)

  2. Advanced Athermal Telescopes, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposed innovative athermal telescope design uses advanced lightweight and high-stiffness material of Beryllium-Aluminum (Be-38Al). Peregrine's expertise with...

  3. Phase camera experiment for Advanced Virgo

    Energy Technology Data Exchange (ETDEWEB)

    Agatsuma, Kazuhiro, E-mail: agatsuma@nikhef.nl [National Institute for Subatomic Physics, Amsterdam (Netherlands); Beuzekom, Martin van; Schaaf, Laura van der [National Institute for Subatomic Physics, Amsterdam (Netherlands); Brand, Jo van den [National Institute for Subatomic Physics, Amsterdam (Netherlands); VU University, Amsterdam (Netherlands)

    2016-07-11

    We report on a study of the phase camera, which is a frequency selective wave-front sensor of a laser beam. This sensor is utilized for monitoring sidebands produced by phase modulations in a gravitational wave (GW) detector. Regarding the operation of the GW detectors, the laser modulation/demodulation method is used to measure mirror displacements and used for the position controls. This plays a significant role because the quality of controls affect the noise level of the GW detector. The phase camera is able to monitor each sideband separately, which has a great benefit for the manipulation of the delicate controls. Also, overcoming mirror aberrations will be an essential part of Advanced Virgo (AdV), which is a GW detector close to Pisa. Especially low-frequency sidebands can be affected greatly by aberrations in one of the interferometer cavities. The phase cameras allow tracking such changes because the state of the sidebands gives information on mirror aberrations. A prototype of the phase camera has been developed and is currently tested. The performance checks are almost completed and the installation of the optics at the AdV site has started. After the installation and commissioning, the phase camera will be combined to a thermal compensation system that consists of CO{sub 2} lasers and compensation plates. In this paper, we focus on the prototype and show some limitations from the scanner performance. - Highlights: • The phase camera is being developed for a gravitational wave detector. • A scanner performance limits the operation speed and layout design of the system. • An operation range was found by measuring the frequency response of the scanner.

  4. Phase camera experiment for Advanced Virgo

    International Nuclear Information System (INIS)

    Agatsuma, Kazuhiro; Beuzekom, Martin van; Schaaf, Laura van der; Brand, Jo van den

    2016-01-01

    We report on a study of the phase camera, which is a frequency selective wave-front sensor of a laser beam. This sensor is utilized for monitoring sidebands produced by phase modulations in a gravitational wave (GW) detector. Regarding the operation of the GW detectors, the laser modulation/demodulation method is used to measure mirror displacements and used for the position controls. This plays a significant role because the quality of controls affect the noise level of the GW detector. The phase camera is able to monitor each sideband separately, which has a great benefit for the manipulation of the delicate controls. Also, overcoming mirror aberrations will be an essential part of Advanced Virgo (AdV), which is a GW detector close to Pisa. Especially low-frequency sidebands can be affected greatly by aberrations in one of the interferometer cavities. The phase cameras allow tracking such changes because the state of the sidebands gives information on mirror aberrations. A prototype of the phase camera has been developed and is currently tested. The performance checks are almost completed and the installation of the optics at the AdV site has started. After the installation and commissioning, the phase camera will be combined to a thermal compensation system that consists of CO 2 lasers and compensation plates. In this paper, we focus on the prototype and show some limitations from the scanner performance. - Highlights: • The phase camera is being developed for a gravitational wave detector. • A scanner performance limits the operation speed and layout design of the system. • An operation range was found by measuring the frequency response of the scanner.

  5. Advances phase-lock techniques

    CERN Document Server

    Crawford, James A

    2008-01-01

    From cellphones to micrprocessors, to GPS navigation, phase-lock techniques are utilized in most all modern electronic devices. This high-level book takes a systems-level perspective, rather than circuit-level, which differentiates it from other books in the field.

  6. Betatron phase advance measurement at SPEAR

    International Nuclear Information System (INIS)

    Morton, P.L.; Pellegrin, J.L.; Raubenheimer, T.; Ross, M.

    1987-02-01

    There are many reasons to determine the betatron phase advance between two azimuthal positions in a circular accelerator or storage ring. We have measured the betatron phase advance between various pairs of azimuthal points in the SPEAR Storage Ring by two different methods. The first method is to excite a steady state coherent betatron oscillation with a network analyzer. The second method is to excite a free coherent betatron oscillation with an impulse kick, and to digitally sample the transverse position of the beam at the pickup stations. The results of these digital samples are Fourier analyzed with a computer to obtain the phase advance. The second method is discussed, and the experimental results compared to theory

  7. Betatron phase advance measurement at SPEAR

    International Nuclear Information System (INIS)

    Morton, P.L.; Pellegrin, J.L.; Raubenheimer, T.; Ross, M.

    1987-01-01

    There are many reasons to determine the betatron phase advance between two azimuthal positions in a circular accelerator or storage ring. The authors measured the betatron phase advance between various pairs of azimuthal points in the SPEAR Storage Ring by two different methods. The first method is to excite a steady state coherent betatron oscillation with a network analyzer. The second method is to excite a free coherent betatron oscillation with an impulse kick, and to digitally sample the transverse position of the beam at the pickup stations. The results of these digital samples are Fourier analyzed with a computer to obtain the phase advance. The second method is discussed, and the experimental results compared to theory

  8. Advanced Gouy phase high harmonics interferometer

    Science.gov (United States)

    Mustary, M. H.; Laban, D. E.; Wood, J. B. O.; Palmer, A. J.; Holdsworth, J.; Litvinyuk, I. V.; Sang, R. T.

    2018-05-01

    We describe an extreme ultraviolet (XUV) interferometric technique that can resolve ∼100 zeptoseconds (10‑21 s) delay between high harmonic emissions from two successive sources separated spatially along the laser propagation in a single Gaussian beam focus. Several improvements on our earlier work have been implemented in the advanced interferometer. In this paper, we report on the design, characterization and optimization of the advanced Gouy phase interferometer. Temporal coherence for both atomic argon and molecular hydrogen gases has been observed for several harmonic orders. It has been shown that phase shift of XUV pulses mainly originates from the emission time delay due to the Gouy phase in the laser focus and the observed interference is independent of the generating medium. This interferometer can be a useful tool for measuring the relative phase shift between any two gas species and for studying ultrafast dynamics of their electronic and nuclear motion.

  9. Testing for significance of phase synchronisation dynamics in the EEG.

    Science.gov (United States)

    Daly, Ian; Sweeney-Reed, Catherine M; Nasuto, Slawomir J

    2013-06-01

    A number of tests exist to check for statistical significance of phase synchronisation within the Electroencephalogram (EEG); however, the majority suffer from a lack of generality and applicability. They may also fail to account for temporal dynamics in the phase synchronisation, regarding synchronisation as a constant state instead of a dynamical process. Therefore, a novel test is developed for identifying the statistical significance of phase synchronisation based upon a combination of work characterising temporal dynamics of multivariate time-series and Markov modelling. We show how this method is better able to assess the significance of phase synchronisation than a range of commonly used significance tests. We also show how the method may be applied to identify and classify significantly different phase synchronisation dynamics in both univariate and multivariate datasets.

  10. Two pedigrees of familial advanced sleep phase syndrome in Japan.

    Science.gov (United States)

    Satoh, Kohtoku; Mishima, Kazuo; Inoue, Yuichi; Ebisawa, Takashi; Shimizu, Tetsuo

    2003-06-15

    To determine whether a known missense mutation (bp2106 A/G) in hPer2 (a human homolog of the Drosophila period gene) for familial advanced sleep phase syndrome in a Caucasian family is involved in Japanese familial advanced sleep phase syndrome pedigrees. We identified 2 new Japanese families with advanced sleep phase syndrome, and a systematic survey was carried out in 28 relatives of theses 2 families. A total of 9 affected subjects were identified. The affected members showed significantly strong morningness tendencies compared with the unaffected members in various circadian parameters including the Horne-Ostberg Morningness-Eveningness Questionnaire score (77.3 +/- 4.8 vs 57.5 +/- 7.6, p sleep-onset time (20:45 +/- 75 min vs 23:16 +/- 64 min, p DNA samples were obtained from 7 affected and 7 unaffected subjects. None of the tested subjects possessed the missense mutation (bp2106 A/G) in hPer2. Furthermore, there is no significant linkage between affected subjects with hPer2 region by 2-point mapping and by direct sequencing of 23 exons of hPer2. These findings support the notion of genetic heterogeneity of familial advanced sleep phase syndrome cases in humans. The search for more familial advanced sleep phase syndrome cases and for loci other than hPer2 are necessary to further examine the roles of circadian-related genes in genetically determined human circadian rhythm disorders.

  11. Prognostic significance of obstructive uropathy in advanced prostate cancer.

    Science.gov (United States)

    Oefelein, Michael G

    2004-06-01

    To report the incidence and prognostic implications of obstructive uropathy (OU) in patients with advanced prostate cancer receiving androgen deprivation therapy and to define the impact initial local therapy has on the development of OU in patients with prostate cancer who develop recurrence and begin androgen deprivation therapy. From a population of 260 patients with advanced prostate cancer diagnosed between 1986 and 2003, OU was identified in 51 patients. The OU treatment options included ureteral stent, percutaneous nephrostomy, transurethral resection of the prostate, Foley catheter placement, and urinary diversion. Overall survival and the factors that influenced survival were calculated using standard statistical methods. OU was diagnosed in 15 (16%) of 80 patients who received local therapy with curative intent and in whom local therapy subsequently failed and in 36 (19%) of 180 patients who had never received local therapy (P = 0.7, chi-square test). Of these 51 patients, 39 had bladder neck obstruction and 16 had ureteral obstruction. Overall survival was significantly worse for the men with OU compared with those without OU (41 versus 54 months). OU was associated with tumor stage and androgen-insensitive prostate cancer. OU results in significantly reduced survival in men with prostate cancer. In a select group of patients with prostate cancer with progression after local therapy (primarily radiotherapy), no statistically significant reduction in the development of OU was observed relative to patients matched for stage, grade, and pretreatment prostate-specific antigen level treated with androgen deprivation therapy alone. Aggressive advanced stage and hormone-insensitive disease are variables associated with OU.

  12. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    International Nuclear Information System (INIS)

    Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

    2013-01-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  13. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  14. Computational advances in transition phase analysis

    International Nuclear Information System (INIS)

    Morita, K.; Kondo, S.; Tobita, Y.; Shirakawa, N.; Brear, D.J.; Fischer, E.A.

    1994-01-01

    In this paper, historical perspective and recent advances are reviewed on computational technologies to evaluate a transition phase of core disruptive accidents in liquid-metal fast reactors. An analysis of the transition phase requires treatment of multi-phase multi-component thermohydraulics coupled with space- and energy-dependent neutron kinetics. Such a comprehensive modeling effort was initiated when the program of SIMMER-series computer code development was initiated in the late 1970s in the USA. Successful application of the latest SIMMER-II in USA, western Europe and Japan have proved its effectiveness, but, at the same time, several areas that require further research have been identified. Based on the experience and lessons learned during the SIMMER-II application through 1980s, a new project of SIMMER-III development is underway at the Power Reactor and Nuclear Fuel Development Corporation (PNC), Japan. The models and methods of SIMMER-III are briefly described with emphasis on recent advances in multi-phase multi-component fluid dynamics technologies and their expected implication on a future reliable transition phase analysis. (author)

  15. Prognostic significance of symptoms of hospitalised advanced cancer patients

    NARCIS (Netherlands)

    Teunissen, Saskia C.; de Graeff, Alexander; de Haes, Hanneke C.; Voest, Emile E.

    2006-01-01

    To assess the prognostic value of symptoms in hospitalised advanced cancer patients. A prospective analysis was performed of 181 hospitalised patients referred to a Palliative Care Team. Comprehensive symptom questionnaire, functional status, estimated life expectancy and survival were assessed.

  16. Innovative Phase Change Approach for Significant Energy Savings

    Science.gov (United States)

    2016-09-01

    related to the production, use, transmission , storage, control, or conservation of energy that will – (A) reduce the need for additional energy supplies...Conditions set for operation were: a. The computer with the broadband wireless card is to be used for data collection, transmission and...FINAL REPORT Innovative Phase Change Approach for Significant Energy Savings ESTCP Project EW-201138 SEPTEMBER 2016 Dr. Aly H Shaaban Applied

  17. Water Phase Diagram Is Significantly Altered by Imidazolium Ionic Liquid

    DEFF Research Database (Denmark)

    Chaban, V. V.; Prezhdo, O. V.

    2014-01-01

    We report unusually large changes in the boiling temperature, saturated vapor pressure, and structure of the liquid-vapor interface for a range of 1-butyl-3-methyl tetrafluoroborate, [C4C1IM][BF4]-water mixtures. Even modest molar fractions of [C4C1IM][BF4] significantly affect the phase behavior...... of water, as represented, for instance, by strong negative deviations from Raoult's law, extending far beyond the standard descriptions. The investigation was carried out using classical molecular dynamics employing a specifically refined force field. The changes in the liquid-vapor interface and saturated...

  18. Advanced Situation Awareness Technologies, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Situation Awareness Technologies (ASAT) will facilitate exploration of the moon surface, and other planetary bodies. ASAT will create an Advanced Situation...

  19. Advanced Aqueous Phase Catalyst Development using Combinatorial Methods, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Combinatorial methods are proposed to develop advanced Aqueous Oxidation Catalysts (AOCs) with the capability to mineralize organic contaminants present in effluents...

  20. Clinical significant of three phase radionuclide bone scan

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Hee; Suh, Jin Suck; Park, Chang Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1989-04-15

    Three phase radionuclide bone scan, consisting of a radionuclide angiogram, an immediate postinjection blood pool image, and 4hr delayed images, was randomly performed in 182 patients, who had been suffered from either local pain or tenderness. Authors analysed 3 phase bone scan in 74 patients with correct diagnosis proven surgically or clinically, from July 1987 to August, 1988. The results were as follows: 1. Overall sensitivity of 3 phase bone scan was 85.4%: sensitivity in patients with an osseous lesion was 90.4% as opposed to 72.7% in patients with a nonosseous lesion. 2. There was no difference in the detection rate of the osseous lesions between the 3 phase bone scan and the delayed image bone scan. However, because the detection rate was higher on the 3 phase bone scan than it was on only the delayed image bone scan (55%) in instance of the nonosseous lesion, we would suggest that 3 phase bone scan might be obtained in cases suspected of the nonosseous lesions. 3. When the presumptive diagnosis was a bone tumor, sensitivity and specificity for malignancy were 67%, 100% respectively. 4. In differentiating osteomyelitis from cellulitis, sensitivity was 94%, specificity was 100%. 5. 3 phase bone scan was able to provide the precise information about either vasculaturity or localization of lesion in some cases of soft tissue mass and avascular necrosis of hips.

  1. Advanced Mars Water Acquisition System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The Advanced Mars Water Acquisition System (AMWAS) recovers and purifies water from Mars soils for oxygen and fuel production, life support, food production, and...

  2. Advanced Carbothermal Electric Reactor, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC proposes to develop the Advanced Carbothermal Electric (ACE) reactor to efficiently extract oxygen from lunar regolith. Unlike state-of-the-art carbothermal...

  3. Advanced TCCS for Spacesuit Applications, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — A recent trade study showed that active removal of ammonia (NH3) and formaldehyde (CH2O) is crticial to meeting the 24-hr SMAC limits in the advanced space suit...

  4. Advanced Green Micropropulsion System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Systima in collaboration with University of Washington is developing a high performance injection system for advanced green monopropellant AF-M315E micropropulsion...

  5. Advanced Green Micropropulsion System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Systima in collaboration with the University of Washington will develop a high performance, advanced green monopropellant microthruster (0.1 – 1.0 N) for small- and...

  6. Advanced supersonic propulsion study, phase 3

    Science.gov (United States)

    Howlett, R. A.; Johnson, J.; Sabatella, J.; Sewall, T.

    1976-01-01

    The variable stream control engine is determined to be the most promising propulsion system concept for advanced supersonic cruise aircraft. This concept uses variable geometry components and a unique throttle schedule for independent control of two flow streams to provide low jet noise at takeoff and high performance at both subsonic and supersonic cruise. The advanced technology offers a 25% improvement in airplane range and an 8 decibel reduction in takeoff noise, relative to first generation supersonic turbojet engines.

  7. Optimization of the Phase Advance Between RHIC Interaction Points

    CERN Document Server

    Tomas, Rogelio

    2005-01-01

    We consider the scenario of having two identical Interaction Points (IPs) in the Relativistic Heavy Ion Collider (RHIC). The strengths of beam-beam resonances strongly depend on the phase advance between these two IPs and therefore certain phase advances could improve beam lifetime and luminosity. We compute the dynamic aperture as function of the phase advance between these IPs to find the optimum settings. The beam-beam interaction is treated in the weak-strong approximation and a complete non-linear model of the lattice is used. For the current RHIC proton working point (0.69,0.685) the design lattice is found to have the optimum phase advance. However this is not the case for other working points.

  8. Traveling wave accelerating structures with a large phase advance

    International Nuclear Information System (INIS)

    Paramonov, V.V.

    2012-01-01

    The cells RF parameters for the well known Disk Loaded Waveguide (DLW) are considered in higher pass bands of TM01 wave, providing operating phase advance between 180 o - 1230 o per cell. With an appropriate shape optimization and some additional elements proposed traveling wave structures with such large phase advance overlap the classical first band DLW in RF efficiency. Examples of proposed structures together with RF and dispersion properties are presented.

  9. Advanced Gearless Drivetrain - Phase I Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Butterfield, Sandy; Smith, Jim; Petch, Derek; Sullivan, Brian; Smith, Peter; Pierce, Kirk

    2012-08-31

    Boulder Wind Power (BWP) collaborated with the National Renewable Energy Laboratory (NREL) in Golden, Colorado, to demonstrate the economics of scaling an advanced gearless drivetrain technology to 6MW (and larger) turbine applications. The project goal was to show that this advanced drivetrain technology enables a cost of energy of less than $0.10/kWH in offshore applications. This drivetrain technology achieves this Cost of Energy (COE) advantage via a 70% greater torque density versus current state-of-the-art drivetrain technologies. In addition, a new dynamically compliant design strategy is required to optimize turbine system-level COE. The BWP generator is uniquely suited for this new design strategy. This project developed a concept design for a 6MW drivetrain and culminated in a plan for a system-level test of this technology at 3MW scale. The project further demonstrated the advantage of the BWP drivetrain with increasing power ratings, with conceptual designs through 10 MW.

  10. Advanced supersonic propulsion study, phase 4

    Science.gov (United States)

    Howlett, R. A.

    1977-01-01

    Installation characteristics for a Variable Stream Control Engine (VSCE) were studied for three advanced supersonic airplane designs. Sensitivity of the VSCE concept to change in technology projections was evaluated in terms of impact on overall installed performance. Based on these sensitivity results, critical technology requirements were reviewed, resulting in the reaffirmation of the following requirements: low-noise nozzle system; a high performance, low emissions duct burner and main burner; hot section technology; variable geometry components; and propulsion integration features, including an integrated electronic control system.

  11. Dynamics Assessment of Advanced Single-Phase PLL Structures

    DEFF Research Database (Denmark)

    Golestan, Saeed; Monfarad, Mohammad; Freijedo, Francisco D.

    2013-01-01

    Recently, several advanced phase locked loop (PLL) techniques have been proposed for single-phase applications. Among these, the Park-PLL, and the second order generalized integrator (SOGI) based PLL are very attractive, owing to their simple digital implementation, low computational burden...

  12. Advanced frequency synthesis by phase lock

    CERN Document Server

    Egan, William F

    2011-01-01

    "An addendum to the popular Frequency Synthesis by Phase Lock, 2nd ed, this book describes sigma-delta, a frequency synthesis technique that has gained prominence in recent years. In addition, Simulink will be employed extensively to guide the reader. Fractional-n, the still-used forerunner to sigma-delta, is also discussed. Sequences of simulated results allow the reader to gain a deeper understanding while detailed appendices provide information from various stages of development. Simulation models discussed in the chapters that are available online."--Provided by publisher.

  13. Digital polarization holography advancing geometrical phase optics.

    Science.gov (United States)

    De Sio, Luciano; Roberts, David E; Liao, Zhi; Nersisyan, Sarik; Uskova, Olena; Wickboldt, Lloyd; Tabiryan, Nelson; Steeves, Diane M; Kimball, Brian R

    2016-08-08

    Geometrical phase or the fourth generation (4G) optics enables realization of optical components (lenses, prisms, gratings, spiral phase plates, etc.) by patterning the optical axis orientation in the plane of thin anisotropic films. Such components exhibit near 100% diffraction efficiency over a broadband of wavelengths. The films are obtained by coating liquid crystalline (LC) materials over substrates with patterned alignment conditions. Photo-anisotropic materials are used for producing desired alignment conditions at the substrate surface. We present and discuss here an opportunity of producing the widest variety of "free-form" 4G optical components with arbitrary spatial patterns of the optical anisotropy axis orientation with the aid of a digital spatial light polarization converter (DSLPC). The DSLPC is based on a reflective, high resolution spatial light modulator (SLM) combined with an "ad hoc" optical setup. The most attractive feature of the use of a DSLPC for photoalignment of nanometer thin photo-anisotropic coatings is that the orientation of the alignment layer, and therefore of the fabricated LC or LC polymer (LCP) components can be specified on a pixel-by-pixel basis with high spatial resolution. By varying the optical magnification or de-magnification the spatial resolution of the photoaligned layer can be adjusted to an optimum for each application. With a simple "click" it is possible to record different optical components as well as arbitrary patterns ranging from lenses to invisible labels and other transparent labels that reveal different images depending on the side from which they are viewed.

  14. High Performance Thrusters for Advanced Green Monopropellants, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The development of an advanced green monopropellant propulsion system could have significant benefits to a wide range of NASA space missions, from deep space...

  15. The relationship between bioelectrical impedance phase angle and subjective global assessment in advanced colorectal cancer

    Directory of Open Access Journals (Sweden)

    Grutsch James F

    2008-06-01

    Full Text Available Abstract Background Bioelectrical Impedance (BIA derived phase angle is increasingly being used as an objective indicator of nutritional status in advanced cancer. Subjective Global Assessment (SGA is a subjective method of nutritional status. The objective of this study was to investigate the association between BIA derived phase angle and SGA in advanced colorectal cancer. Methods We evaluated a case series of 73 stages III and IV colorectal cancer patients. Patients were classified as either well-nourished or malnourished using the SGA. BIA was conducted on all patients and phase angle was calculated. The correlation between phase angle and SGA was studied using Spearman correlation coefficient. Receiver Operating Characteristic curves were estimated using the non-parametric method to determine the optimal cut-off levels of phase angle. Results Well-nourished patients had a statistically significantly higher (p = 0.005 median phase angle score (6.12 as compared to those who were malnourished (5.18. The Spearman rank correlation coefficient between phase angle and SGA was found to be 0.33 (p = 0.004, suggesting better nutritional status with higher phase angle scores. A phase angle cut-off of 5.2 was 51.7% sensitive and 79.5% specific whereas a cut-off of 6.0 was 82.8% sensitive and 54.5% specific in detecting malnutrition. Interestingly, a phase angle cut-off of 5.9 demonstrated high diagnostic accuracy in males who had failed primary treatment for advanced colorectal cancer. Conclusion Our study suggests that bioimpedance phase angle is a potential nutritional indicator in advanced colorectal cancer. Further research is needed to elucidate the optimal cut-off levels of phase angle that can be incorporated into the oncology clinic for better nutritional evaluation and management.

  16. Advanced Simulation Capability for Environmental Management (ASCEM) Phase II Demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Freshley, M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hubbard, S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Flach, G. [Savannah River National Lab. (SRNL), Aiken, SC (United States); Freedman, V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Agarwal, D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Andre, B. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Bott, Y. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Chen, X. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Davis, J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Faybishenko, B. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gorton, I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Murray, C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moulton, D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Meyer, J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rockhold, M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Shoshani, A. [LBNL; Steefel, C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wainwright, H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Waichler, S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2012-09-28

    In 2009, the National Academies of Science (NAS) reviewed and validated the U.S. Department of Energy Office of Environmental Management (EM) Technology Program in its publication, Advice on the Department of Energy’s Cleanup Technology Roadmap: Gaps and Bridges. The NAS report outlined prioritization needs for the Groundwater and Soil Remediation Roadmap, concluded that contaminant behavior in the subsurface is poorly understood, and recommended further research in this area as a high priority. To address this NAS concern, the EM Office of Site Restoration began supporting the development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific approach that uses an integration of toolsets for understanding and predicting contaminant fate and transport in natural and engineered systems. The ASCEM modeling toolset is modular and open source. It is divided into three thrust areas: Multi-Process High Performance Computing (HPC), Platform and Integrated Toolsets, and Site Applications. The ASCEM toolsets will facilitate integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. During fiscal year 2012, the ASCEM project continued to make significant progress in capabilities development. Capability development occurred in both the Platform and Integrated Toolsets and Multi-Process HPC Simulator areas. The new Platform and Integrated Toolsets capabilities provide the user an interface and the tools necessary for end-to-end model development that includes conceptual model definition, data management for model input, model calibration and uncertainty analysis, and model output processing including visualization. The new HPC Simulator capabilities target increased functionality of process model representations, toolsets for interaction with the Platform, and model confidence testing and verification for

  17. Management of Advanced-Phase Chronic Myelogenous Leukemia.

    Science.gov (United States)

    Radich, Jerald P

    2016-05-01

    Chronic myelogenous leukemia represents the poster child of successful precision medicine in cancer, with amazing survival results achieved with targeted tyrosine kinase inhibitors (TKIs) in many patients with chronic-phase disease. Unfortunately, however, this good news has not extended to patients in blast crisis, for whom survival has not clearly been improved with TKIs. During his presentation at the NCCN 21st Annual Conference, Jerald P. Radich, MD, briefly explored the biology behind advanced-stage disease and several of the molecular findings in disease progression. He also reviewed some of the therapeutic options in advanced disease, emphasizing that transplantation, although fraught with some difficulties, offers the best long-term prognosis for patients in blast crisis. Copyright © 2016 by the National Comprehensive Cancer Network.

  18. FreedomCAR Advanced Traction Drive Motor Development Phase I

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Josh (UQM Technologies, Inc.); Lutz, Jon (UQM Technologies, Inc.)

    2006-09-01

    The overall objective of this program is to design and develop an advanced traction motor that will meet the FreedomCAR and Vehicle Technologies (FCVT) 2010 goals and the traction motor technical targets. The motor specifications are given in Section 1.3. Other goals of the program include providing a cost study to ensure the motor can be developed within the cost targets needed for the automotive industry. The program has focused on using materials that are both high performance and low costs such that the performance can be met and cost targets are achieved. In addition, the motor technologies and machine design features must be compatible with high volume manufacturing and able to provide high reliability, efficiency, and ruggedness while simultaneously reducing weight and volume. Weight and volume reduction will become a major factor in reducing cost, material cost being the most significant part of manufacturing cost at high volume. Many motor technology categories have been considered in the past and present for traction drive applications, including: brushed direct current (DC), PM (PM) brushless dc (BLDC), alternating current (AC) induction, switched reluctance and synchronous reluctance machines. Of these machine technologies, PM BLDC has consistently demonstrated an advantage in terms of power density and efficiency. As rare earth magnet cost has declined, total cost may also be reduced over the other technologies. Of the many different configurations of PM BLDC machines, those which incorporate power production utilizing both magnetic torque as well as reluctance torque appear to have the most promise for traction applications. There are many different PM BLDC machine configurations which employ both of these torque producing mechanisms; however, most would fall into one of two categories--some use weaker magnets and rely more heavily on reluctance torque (reluctance-dominant PM machines), others use strong PMs and supplement with reluctance torque

  19. Prognostic factors in advanced breast cancer: Race and receptor status are significant after development of metastasis.

    Science.gov (United States)

    Ren, Zhiyong; Li, Yufeng; Shen, Tiansheng; Hameed, Omar; Siegal, Gene P; Wei, Shi

    2016-01-01

    Prognostic factors are well established in early-stage breast cancer (BC), but less well-defined in advanced disease. We analyzed 323 BC patients who had distant relapse during follow-up from 1997 to 2010 to determine the significant clinicopathologic factors predicting survival outcomes. By univariate analysis, race, tumor grade, estrogen and progesterone receptors (ER/PR) and HER2 status were significantly associated with overall survival (OS) and post-metastasis survival (PMS). Applying a Cox regression model revealed that all these factors remained significant for PMS, while race, tumor grade and HER2 were independent factors for OS. Tumor grade was the only significant factor for metastasis-free survival by univariate and multivariate analyses. Our findings demonstrated that being Caucasian, hormonal receptor positive (HR+) and HER2 positive (HER2+) were all associated with a decreased hazard of death and that patients with HR+/HER2+ tumors had superior outcomes to those with HR+/HER2- disease. Further, PR status held a prognostic value over ER, thus reflecting the biologic mechanism of the importance of the functional ER pathway and the heterogeneity in the response to endocrine therapy. These observations indicate that the patients' genetic makeup and the intrinsic nature of the tumor principally govern BC progression and prognosticate the long-term outcomes in advanced disease. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Recent Advances on Neuromorphic Systems Using Phase-Change Materials

    Science.gov (United States)

    Wang, Lei; Lu, Shu-Ren; Wen, Jing

    2017-05-01

    Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

  1. Recent Advances on Neuromorphic Systems Using Phase-Change Materials.

    Science.gov (United States)

    Wang, Lei; Lu, Shu-Ren; Wen, Jing

    2017-12-01

    Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

  2. Serum Advanced Oxidation Protein Products in Oral Squamous Cell Carcinoma: Possible Markers of Diagnostic Significance

    Directory of Open Access Journals (Sweden)

    Abhishek Singh Nayyar

    2013-07-01

    Full Text Available Background: The aim of this study was to measure the concentrations (levels ofserum total proteins and advanced oxidation protein products as markers of oxidantmediated protein damage in the sera of patients with oral cancers.Methods: The study consisted of the sera analyses of serum total protein andadvanced oxidation protein products’ levels in 30 age and sex matched controls, 60patients with reported pre-cancerous lesions and/or conditions and 60 patients withhistologically proven oral squamous cell carcinoma. One way analyses of variance wereused to test the difference between groups. To determine which of the two groups’ meanswere significantly different, the post-hoc test of Bonferroni was used. The results wereaveraged as mean ± standard deviation. In the above test, P values less than 0.05 weretaken to be statistically significant. The normality of data was checked before thestatistical analysis was performed.Results: The study revealed statistically significant variations in serum levels ofadvanced oxidation protein products (P<0.001. Serum levels of total protein showedextensive variations; therefore the results were largely inconclusive and statisticallyinsignificant.Conclusion: The results emphasize the need for more studies with larger samplesizes to be conducted before a conclusive role can be determined for sera levels of totalprotein and advanced oxidation protein products as markers both for diagnosticsignificance and the transition from the various oral pre-cancerous lesions and conditionsinto frank oral cancers.

  3. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    Directory of Open Access Journals (Sweden)

    Behl Susanne

    2008-03-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

  4. Significance of Metabolic Super scan in Patients With Locally Advanced Bladder Cancer

    International Nuclear Information System (INIS)

    Kotb, M.H.; El-Kholy, E.; Omar, W.; El-Refaei, S.; Taher, A.N.; El-Marakby, H.

    2011-01-01

    was more frequent in patients with SCC (P<0.001). Out of 401 documented bone lesions, 302 proved to be metabolic related, 97 metastatic and 2 non-metabolic benign bone lesions. The sensitivity and specificity of bone scanning in documentation of bone lesions were 100% and 91%, respectively. Serum creatinine level for metabolic group was significantly elevated (3.91 ± 1.76 compared to 1.16 ± 0.47 and 1.07 ± 0.5) for normal and metastatic groups, respectively (P<0.001). Back pressure changes were significantly higher in metabolic group (90%) compared to 20% and 17% for normal and metastatic groups, respectively (P<0.001). Regarding the mortality rate, no difference was found between the metabolic and normal groups (15.7% and 15.2%, respectively) while patients in the metabolic group showed a much higher incidence of morbidity as compared to the normal group. It could be concluded that the disturbance in bone metabolism is strongly evident in locally advanced bladder cancer patients with renal impairment. Metabolic bone changes seem to be higher in SCC patients as compared to TCC. MSS features are significantly better than bio markers in detection of metabolic changes. Integration of bone scan in the diagnostic work up of locally advanced bladder cancer is a simple reliable tool of dual benefit that may improve patient management through monitoring and differentiating between metabolic changes and skeletal metastases

  5. Safety significance of ATR [Advanced Test Reactor] passive safety response attributes

    International Nuclear Information System (INIS)

    Atkinson, S.A.

    1989-01-01

    The Advanced Test Reactor (ATR) at the Idaho National Engineering Laboratory was designed with some passive safety response attributes which contribute to the safety posture of the facility. The three passive safety attributes being evaluated in the paper are: (1) In-core and in-vessel natural convection cooling, (2) a passive heat sink capability of the ATR primary coolant system (PCS) for the transfer of decay power from the uninsulated piping to the confinement, and (3) gravity feed of emergency coolant makeup. The safety significance of the ATR passive safety response attributes is that the reactor can passively respond for most transients, given a reactor scram, to provide adequate decay power removal and a significant time for operator action should the normal active heat removal systems and their backup systems both fail. The ATR Interim Level 1 Probabilistic Risk Assessment (PRA) model ands results were used to evaluate the significance to ATR fuel damage frequency (or probability) of the above three passive response attributes. The results of the evaluation indicate that the first attribute is a major safety characteristic of the ATR. The second attribute has a noticeable but only minor safety significance. The third attribute has no significant influence on the ATR Level 1 PRA because of the diversity and redundancy of the ATR firewater injection system (emergency coolant system). 8 refs., 4 figs., 1 tab

  6. Recent advances in synchrotron-based hard x-ray phase contrast imaging

    Science.gov (United States)

    Liu, Y.; Nelson, J.; Holzner, C.; Andrews, J. C.; Pianetta, P.

    2013-12-01

    Ever since the first demonstration of phase contrast imaging (PCI) in the 1930s by Frits Zernike, people have realized the significant advantage of phase contrast over conventional absorption-based imaging in terms of sensitivity to ‘transparent’ features within specimens. Thus, x-ray phase contrast imaging (XPCI) holds great potential in studies of soft biological tissues, typically containing low Z elements such as C, H, O and N. Particularly when synchrotron hard x-rays are employed, the favourable brightness, energy tunability, monochromatic characteristics and penetration depth have dramatically enhanced the quality and variety of XPCI methods, which permit detection of the phase shift associated with 3D geometry of relatively large samples in a non-destructive manner. In this paper, we review recent advances in several synchrotron-based hard x-ray XPCI methods. Challenges and key factors in methodological development are discussed, and biological and medical applications are presented.

  7. Recent advances in synchrotron-based hard x-ray phase contrast imaging

    International Nuclear Information System (INIS)

    Liu, Y; Nelson, J; Andrews, J C; Pianetta, P; Holzner, C

    2013-01-01

    Ever since the first demonstration of phase contrast imaging (PCI) in the 1930s by Frits Zernike, people have realized the significant advantage of phase contrast over conventional absorption-based imaging in terms of sensitivity to ‘transparent’ features within specimens. Thus, x-ray phase contrast imaging (XPCI) holds great potential in studies of soft biological tissues, typically containing low Z elements such as C, H, O and N. Particularly when synchrotron hard x-rays are employed, the favourable brightness, energy tunability, monochromatic characteristics and penetration depth have dramatically enhanced the quality and variety of XPCI methods, which permit detection of the phase shift associated with 3D geometry of relatively large samples in a non-destructive manner. In this paper, we review recent advances in several synchrotron-based hard x-ray XPCI methods. Challenges and key factors in methodological development are discussed, and biological and medical applications are presented. (paper)

  8. Small airway function changes and its clinical significance of asthma patients in different clinical phases

    Directory of Open Access Journals (Sweden)

    Yan-Hui Zhou

    2016-11-01

    Full Text Available Objective: To observe the small airways function changes of asthmatic patients in different clinical phases and to discuss its clinical significance. Methods: A total of 127 patients diagnosed as asthma were selected randomly and pulmonary function (PF of them was determined by conventional method. Then they were divided into A, B and C group based on PF results. All 34 patients in A group suffered from acute asthma attack for the first time. All 93 patients in B group had been diagnosed as asthma but in remission phase. C Group was regarded as Control group with 20 healthy volunteers. Then FEV1, FEF50%, FEF75% levels of patients in each group were analyzed, and ΔFEV1, ΔFEF75% and ΔFEF50% levels of patients in each group were compared after bronchial dilation test. Results: It was found that most patients in group A and B had abnormal small airways function, and their small airways function was significantly different compared with that of group C (P<0.01. In addition, except for group C, ΔFEF75%,ΔFEF50% levels in A and B group were improved more significantly than ΔFEV1 levels (P<0.01. Conclusions: Asthma patients in acute phase all have abnormal small airways function. Most asthma patients in remission phase also have abnormal small airways function. After bronchial dilation test, whether patients in acute phase or in remission phase, major and small airways function of them are improved, but improvement of small airways function is weaker than that of major airways. This indicates that asthma respiratory tract symptoms in different phases exists all the time and so therapeutic process is needed to perform step by step.

  9. A Review of Significant Advances in Neutron Imaging from Conception to the Present

    Science.gov (United States)

    Brenizer, J. S.

    This review summarizes the history of neutron imaging with a focus on the significant events and technical advancements in neutron imaging methods, from the first radiograph to more recent imaging methods. A timeline is presented to illustrate the key accomplishments that advanced the neutron imaging technique. Only three years after the discovery of the neutron by English physicist James Chadwick in 1932, neutron imaging began with the work of Hartmut Kallmann and Ernst Kuhn in Berlin, Germany, from 1935-1944. Kallmann and Kuhn were awarded a joint US Patent issued in January 1940. Little progress was made until the mid-1950's when Thewlis utilized a neutron beam from the BEPO reactor at Harwell, marking the beginning of the application of neutron imaging to practical applications. As the film method was improved, imaging moved from a qualitative to a quantitative technique, with applications in industry and in nuclear fuels. Standards were developed to aid in the quantification of the neutron images and the facility's capabilities. The introduction of dynamic neutron imaging (initially called real-time neutron radiography and neutron television) in the late 1970's opened the door to new opportunities and new challenges. As the electronic imaging matured, the introduction of the CCD imaging devices and solid-state light intensifiers helped address some of these challenges. Development of improved imaging devices for the medical community has had a major impact on neutron imaging. Additionally, amorphous silicon sensors provided improvements in temporal resolution, while providing a reasonably large imaging area. The development of new neutron imaging sensors and the development of new neutron imaging techniques in the past decade has advanced the technique's ability to provide insight and understanding of problems that other non-destructive techniques could not provide. This rapid increase in capability and application would not have been possible without the

  10. Lifted linear phase filter banks and the polyphase-with-advance representation

    Energy Technology Data Exchange (ETDEWEB)

    Brislawn, C. M. (Christopher M.); Wohlberg, B. E. (Brendt E.)

    2004-01-01

    A matrix theory is developed for the noncausal polyphase-with-advance representation that underlies the theory of lifted perfect reconstruction filter banks and wavelet transforms as developed by Sweldens and Daubechies. This theory provides the fundamental lifting methodology employed in the ISO/IEC JPEG-2000 still image coding standard, which the authors helped to develop. Lifting structures for polyphase-with-advance filter banks are depicted in Figure 1. In the analysis bank of Figure 1(a), the first lifting step updates x{sub 0} with a filtered version of x{sub 1} and the second step updates x{sub 1} with a filtered version of x{sub 0}; gain factors 1/K and K normalize the lowpass- and highpass-filtered output subbands. Each of these steps is inverted by the corresponding operations in the synthesis bank shown in Figure 1(b). Lifting steps correspond to upper- or lower-triangular matrices, S{sub i}(z), in a cascade-form decomposition of the polyphase analysis matrix, H{sub a}(z). Lifting structures can also be implemented reversibly (i.e., losslessly in fixed-precision arithmetic) by rounding the lifting updates to integer values. Our treatment of the polyphase-with-advance representation develops an extensive matrix algebra framework that goes far beyond the results of. Specifically, we focus on analyzing and implementing linear phase two-channel filter banks via linear phase lifting cascade schemes. Whole-sample symmetric (WS) and half-sample symmetric (HS) linear phase filter banks are characterized completely in terms of the polyphase-with-advance representation. The theory benefits significantly from a number of new group-theoretic structures arising in the polyphase-with-advance matrix algebra from the lifting factorization of linear phase filter banks.

  11. What is the significance of the circumferential margin in locally advanced rectal cancer after neoadjuvant chemoradiotherapy?

    Science.gov (United States)

    Trakarnsanga, Atthaphorn; Gonen, Mithat; Shia, Jinru; Goodman, Karyn A; Nash, Garrett M; Temple, Larissa K; Guillem, José G; Paty, Philip B; Garcia-Aguilar, Julio; Weiser, Martin R

    2013-04-01

    The circumferential resection margin (CRM) is highly prognostic for local recurrence in rectal cancer surgery without neoadjuvant treatment. However, its significance in the setting of long-course neoadjuvant chemoradiotherapy (nCRT) is not well defined. Review of a single institution's prospectively maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/T4 and/or N1) receiving nCRT, followed after 6 weeks by total mesorectal excision (TME). Kaplan-Meier, Cox regression, and competing risk analysis were performed. The authors noted that 75 % of all patients had stage III disease as determined by endorectal ultrasound (ERUS) and/or magnetic resonance imaging (MRI). With median follow-up of 39 months after resection, local and distant relapse were noted in 12 (2.1 %) and 98 (17.4 %) patients, respectively. On competing risk analysis, the optimal cutoff point of CRM was 1 mm for local recurrence and 2 mm for distant metastasis. Factors independently associated with local recurrence included CRM ≤1 mm, and high-grade tumor (p = 0.012 and 0.007, respectively). CRM ≤2 mm, as well as pathological, nodal, and overall tumor stage are also significant independent risk factors for distant metastasis (p = 0.025, 0.010, and dataset of locally advanced rectal cancer treated with nCRT followed by TME, CRM ≤1 mm is an independent risk factor for local recurrence and is considered a positive margin. CRM ≤2 mm was associated with distant recurrence, independent of pathological tumor and nodal stage.

  12. Prognostic significance of clinical and pathological stages on locally advanced rectal carcinoma after neoadjuvant chemoradiotherapy

    International Nuclear Information System (INIS)

    Wen, Bixiu; Zhang, Luning; Wang, Chengtao; Huang, Rong; Peng, Haihua; Zhang, Tian; Dong, Jun; Xiao, Weiwei; Zeng, Zhifan; Liu, Mengzhong; Gao, Yuanhong

    2015-01-01

    To investigate prognostic significance of clinical and pathological stages in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy (neo-CRT) and total mesorectal excision. 210 patients with locally advanced rectal carcinoma (cT3-4 or cN+) treated with neo-CRT followed by total mesorectal excision. Treatment outcomes were compared according to clinical and pathological stage. Overall survival (OS), disease free survival (DFS) among patients with different clinical stage and pathological stage after neo-CRT. The median follow-up time was 47 months (range, 14–98 months). Clinical T stage was associated with 5 year OS (p = 0.042) and 5 year DFS (p = 0.014) while clinical N stage was not associated with 5 year OS (p = 0.440), 5 year DFS (p = 0.711). Pathological T stage was associate with 5 year OS (p = 0.001) and 5 year DFS (p = 0.046); and N stage was associated with 5 year OS (p = 0.001), 5 year DFS (p = 0.002). The pathological stage was further classified into three groups: ypT0–2N0 in 91 patients (43.3 %), ypT3–4N0 in 69 patients (32.9 %) and ypT0–4N+ in 50 patients (23.8 %). While pathological stage (ypT0–2 vs ypT3–4N0 vs ypT0–4N+) was associated with 5 year OS (87.9 %, 75.5 %, 56.7 %, p = 0.000), 5 year DFS (74.5 %, 77.4 %, 50.5 %, p = 0.003). Multivariate analysis showed that ypN stage was an independent prognostic factor for patients 5 year DFS. Pathological stage is strongly associated with treatment outcomes in patients with locally advanced rectal carcinoma treated with neo-CRT followed by total mesorectal excision, which may be used as guidance for further individualized treatment

  13. Prognostic Significance of p16 Expression in Advanced Cervical Cancer Treated With Definitive Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Lewis, James S. [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Pfeifer, John [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Huettner, Phyllis [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Grigsby, Perry [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States)

    2012-09-01

    Purpose: The purpose of this study was to evaluate the prognostic significance of p16 immunohistochemistry (IHC) in patients with advanced cervical cancer treated with radiation therapy. Materials and Methods: This was a retrospective study of 126 patients with International Federation of Gynecology and Obstetrics Stages Ib1-IVb cervical cancer treated with radiation. Concurrent cisplatin chemotherapy was given to 108 patients. A tissue microarray (TMA) was constructed from the paraffin-embedded diagnostic biopsy specimens. Immunoperoxidase staining was performed on the TMA and a p16 monoclonal antibody was utilized. IHC p16 extent was evaluated and scored in quartiles: 0 = no staining, 1 = 1-25% of cells staining, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. Results: The p16 IHC score was 4 in 115 cases, 3 in 1, 2 in 3 and 0 in 7. There was no relationship between p16 score and tumor histology. Patients with p16-negative tumors were older (mean age at diagnosis 65 vs. 52 years for p16-positive tumors; p = 0.01). The 5-year cause-specific survivals were 33% for p16-negative cases (score = 0) compared with 63% for p16-positive cases (scores 1, 2, 3 or 4; p = 0.07). The 5-year recurrence-free survivals were 34% for those who were p16-negative vs. 57% for those who were p16-positive (p = 0.09). In addition, patients with p16-positive tumors (score > 0) were more likely to be complete metabolic responders as assessed by the 3-month posttherapy 18 [F]-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomograph compared with patients with p16-negative tumors (p = 0.03). Conclusion: p16 expression is predictive of improved survival outcome after chemoradiation therapy for advanced-stage invasive cervical carcinoma. Further testing will be needed to evaluate p16-negative cervical tumors.

  14. Confirming the timing of phase-based costing in oncology studies: a case example in advanced melanoma.

    Science.gov (United States)

    Atkins, Michael; Coutinho, Anna D; Nunna, Sasikiran; Gupte-Singh, Komal; Eaddy, Michael

    2018-02-01

    The utilization of healthcare services and costs among patients with cancer is often estimated by the phase of care: initial, interim, or terminal. Although their durations are often set arbitrarily, we sought to establish data-driven phases of care using joinpoint regression in an advanced melanoma population as a case example. A retrospective claims database study was conducted to assess the costs of advanced melanoma from distant metastasis diagnosis to death during January 2010-September 2014. Joinpoint regression analysis was applied to identify the best-fitting points, where statistically significant changes in the trend of average monthly costs occurred. To identify the initial phase, average monthly costs were modeled from metastasis diagnosis to death; and were modeled backward from death to metastasis diagnosis for the terminal phase. Points of monthly cost trend inflection denoted ending and starting points. The months between represented the interim phase. A total of 1,671 patients with advanced melanoma who died met the eligibility criteria. Initial phase was identified as the 5-month period starting with diagnosis of metastasis, after which there was a sharp, significant decline in monthly cost trend (monthly percent change [MPC] = -13.0%; 95% CI = -16.9% to -8.8%). Terminal phase was defined as the 5-month period before death (MPC = -14.0%; 95% CI = -17.6% to -10.2%). The claims-based algorithm may under-estimate patients due to misclassifications, and may over-estimate terminal phase costs because hospital and emergency visits were used as a death proxy. Also, recently approved therapies were not included, which may under-estimate advanced melanoma costs. In this advanced melanoma population, optimal duration of the initial and terminal phases of care was 5 months immediately after diagnosis of metastasis and before death, respectively. Joinpoint regression can be used to provide data-supported phase of cancer care durations, but

  15. The presence of advanced lesions and associating risk factors for advanced cervical carcinoma in patients with atypical sguamous cells of undetermined significance.

    Science.gov (United States)

    Sun, L L; Chen, W; Fan, Y Y; Wang, M L; Wang, L N

    2015-01-01

    To characterize histopathological status, high-risk human papillomavirus (hr-HPV) infection status, and associated risk factors in patients with atypical squamous cells of undetermined significance (ASCUS). Cervical biopsies obtained from 130 ASCUS patients were subjected to histopathological examination and hr-HPV testing. Associations between advanced lesions and hr-HPV load or age were analyzed, and the confounding factors for high-grade cervical lesions were identified. Cervical biopsies from ASCUS patients had a wide range of pathological states, ranging from normal to invasive cervical carcinoma. High-risk HPV infection was significantly associated with advanced cervical lesions in ASCUS patients; hr-HPV infection and the number of gestations were risk factors for developing advanced cervical disease. A significant portion of ASCUS patients harbor advanced cervical lesions. The number of gestations and hr-HPV infection can increase the risk of developing advanced cervical lesions in ASCUS patients.

  16. Raising the Bar: Significant Advances and Future Needs for Promoting Learning for Students with Severe Disabilities

    Science.gov (United States)

    Spooner, Fred; Browder, Diane M.

    2015-01-01

    This essay describes major advances in educating students with severe disabilities. The authors propose that applied behavior analysis, the focus on functional life skills, and the promotion of academic content have been the major advances in the "how" and "what" of learning for this population. An increased focus on literacy,…

  17. Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer.

    Science.gov (United States)

    Paik, E Sun; Kim, Ji Hye; Kim, Tae Joong; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo; Choi, Chel Hun

    2018-01-01

    We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3-164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

  18. The manic phase of Bipolar disorder significantly impairs theory of mind decoding.

    Science.gov (United States)

    Hawken, Emily R; Harkness, Kate L; Lazowski, Lauren K; Summers, David; Khoja, Nida; Gregory, James Gardner; Milev, Roumen

    2016-05-30

    Bipolar disorder is associated with significant deficits in the decoding of others' mental states in comparison to healthy participants. However, differences in theory of mind decoding ability among patients in manic, depressed, and euthymic phases of bipolar disorder is currently unknown. Fifty-nine patients with bipolar I or II disorder (13 manic, 25 depressed, 20 euthymic) completed the "Reading the Mind in the Eyes" Task (Eyes task) and the Animals Task developed to control for non-mentalistic response demands of the Eyes Task. Patients also completed self-report and clinician-rated measures of depression, mania, and anxiety symptoms. Patients in the manic phase were significantly less accurate than those in the depressed and euthymic phases at decoding mental states in the Eyes task, and this effect was strongest for eyes of a positive or neutral valence. Further Eyes task performance was negatively correlated with the symptoms of language/thought disorder, pressured speech, and disorganized thoughts and appearance. These effects held when controlling for accuracy on the Animals task, response times, and relevant demographic and clinical covariates. Results suggest that the state of mania, and particularly psychotic symptoms that may overlap with the schizophrenia spectrum, are most strongly related to social cognitive deficits in bipolar disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Mixed phase clouds: observations and theoretical advances (overview)

    Science.gov (United States)

    Korolev, Alexei

    2013-04-01

    Mixed phase clouds play important role in precipitation formation and radiation budget of the Earth. The microphysical measurements in mixed phase clouds are notoriously difficult due to many technical challenges. The airborne instrumentation for characterization of the microstructure of mixed phase clouds is discussed. The results multiyear airborne observations and measurements of frequency of occurrence of mixed phase, characteristic spatial scales, humidity in mixed phase and ice clouds are presented. A theoretical framework describing the thermodynamics and phase transformation of a three phase component system consisting of ice particles, liquid droplets and water vapor is discussed. It is shown that the Wegener-Bergeron-Findeisen process plays different role in clouds with different dynamics. The problem of maintenance and longevity of mixed phase clouds is discussed.

  20. Evaporation of multicomponent chemical spills: When is liquid phase resistance significant?

    International Nuclear Information System (INIS)

    Berger, D.; Mackay, D.

    1993-01-01

    When chemicals are spilled on land or water, it is important to be able to estimate evaporation rates accurately. Conventional models used to predict evaporation rates of multicomponent spills assume that the entire resistance to evaporation lies in the vapor phase. Under certain conditions, an additional liquid phase resistance may be introduced, resulting in retarded evaporation rates. Existing models may thus fail to predict spill behavior accurately. A study is described whose objective is to elucidate the significance of the liquid phase resistance. Evaporation experiments were conducted in which a thin layer of synthetic oil (mineral oil enriched with compounds such as pentane, hexane, toluene, octane, and p-xylene) was exposed to prolonged evaporation in a metal tray at controlled wind speeds. Bulk samples of the spill layer were taken at specific time intervals and their composition was determined by gas chromatographic analysis. The results are compared to those from a theoretical model and to gas stripping experiments. The model is based on the evaporative flux equation incorporating Raoult's law; inputs are the air-oil partition coefficient for each component and the composition of the synthetic oil on a volume and mole fraction basis. The study has enabled the formation of vertical concentration profiles to be examined and liquid phase mass transfer coefficients to be estimated. The results imply that liquid-phase resistance effects are likely to be important for the most volatile components. Contaminated areas may thus continue to be hazardous, even though model predictions indicate otherwise. 7 refs., 3 figs., 2 tabs

  1. Engineered Materials for Advanced Gas Turbine Engine, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This project will develop innovative composite powders and composites that will surpass the properties of currently identified materials for advanced gas turbine...

  2. Advanced Technology MEMS-based Acoustic Array, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The Interdisciplinary Consulting Corporation proposes a technological advancement of current state-of-the-art acoustic energy harvester for harsh environment...

  3. Advanced Wastewater Photo-oxidation System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Pioneer Astronautics proposes an advanced photocatalytic oxidation reactor for enhancing the reliability and performance of Water Recovery Post Processing systems...

  4. [Clinical significance of prognostic nutritional index in patients with advanced gastric cancer].

    Science.gov (United States)

    Song, Shubin; Liu, Honggang; Xue, Yingwei

    2018-02-25

    To investigate the relationship of prognostic nutritional index (PNI) with clinicopathological factors and the clinical significance of PNI in predicting the survival in patients with advanced gastric cancer. Clinicopathological and follow-up data of 1150 patients with advanced gastric cancer who underwent radical gastrectomy from January 2007 to December 2010 at the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital were analyzed retrospectively. The PNI value was calculated [PNI=absolute value of lymphocyte(10 9 /L)×5 + serum albumin (g/L)] and was grouped according to the mean value of PNI. Relationships of PNI with gender, age, tumor size, depth of invasion, tumor differentiation, tumor stage, tumor location, lymph node metastasis and tumor marker detection level were analyzed. At the same time, for the survival analysis of patients, log-rank method was used for univariate analysis, and Cox method was used for multivariate analysis. Of 1150 cases, 846 were males and 304 were females with an average age of 62 (24 to 88) years. The average maximum diameter of tumor was 5.4(1.0 to 20.0) cm. Tumor of 159 cases located in the gastric fundus, 221 cases in the gastric body, 705 cases in the gastric antrum and 65 cases in the whole stomach. Well differentiated tumors were found in 198 cases and poorly differentiated tumors in 952 cases. As for depth of tumor invasion, 165 cases were T2, 343 cases were T3 and 642 cases were T4. According to TNM stage, 53 cases were stage I(, 397 cases were stage II( and 700 cases were stage III(. The average lymph node metastasis rate was 25.0%, meanwhile lymph node metastasis was N0 in 296 cases, N1 in 246 cases, N2 in 277 cases and N3 in 331 cases. Blood examination showed hemoglobin ≤130 g/L in 544 cases and >130 g/L in 606 cases; carcinoembryonic antigen ≤5 μg/L in 903 cases and >5 μg /L in 247 cases; carbohydrate antigen 19-9 ≤37 kU/L in 927 cases and >37 kU/L in 223 cases. In whole patients

  5. Advanced Industrial Materials (AIM) Program: Compilation of project summaries and significant accomplishments, FY 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-04-01

    In many ways, the Advanced Industrial Materials (AIM) Program underwent a major transformation in Fiscal Year 1995 and these changes have continued to the present. When the Program was established in 1990 as the Advanced Industrial Concepts (AIC) Materials Program, the mission was to conduct applied research and development to bring materials and processing technologies from the knowledge derived from basic research to the maturity required for the end use sectors for commercialization. In 1995, the Office of Industrial Technologies (OIT) made radical changes in structure and procedures. All technology development was directed toward the seven ``Vision Industries`` that use about 80% of industrial energy and generated about 90% of industrial wastes. The mission of AIM has, therefore, changed to ``Support development and commercialization of new or improved materials to improve productivity, product quality, and energy efficiency in the major process industries.`` Though AIM remains essentially a National Laboratory Program, it is essential that each project have industrial partners, including suppliers to, and customers of, the seven industries. Now, well into FY 1996, the transition is nearly complete and the AIM Program remains reasonably healthy and productive, thanks to the superb investigators and Laboratory Program Managers. This report contains the technical details of some very remarkable work by the best materials scientists and engineers in the world. Subject areas covered are: advanced metals and composites; advanced ceramics and composites; polymers and biobased materials; and new materials and processes.

  6. Advanced Insulation Materials for Cryogenic Propellant Storage Applications, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Materials Technology, Inc responds to the NASA solicitation Topic X9 entitled "Propulsion and Propellant Storage" under subtopic X9-01, "Long Term Cryogenic...

  7. Modular Advanced Networked Telerobotic Interface System (MANTIS), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — With the goal to reduce astronaut time required to operate experiments on the ISS and advance automated and telerobotic technology, TUI proposes to collaborate with...

  8. Advanced Gas Sensing Technology for Space Suits, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced space suits require lightweight, low-power, durable sensors for monitoring critical life support materials. No current compact sensors have the tolerance...

  9. Advanced Onboard Energy Storage Solution for Balloons, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Balloon Programs at NASA are looking for a potential 100 day missions at mid-altitudes. These balloons would be powered by solar panels to take advantage of...

  10. Advanced Vortex Hybrid Rocket Engine (AVHRE), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC proposes to develop a unique Advanced Vortex Hybrid Rocket Engine (AVHRE) to achieve a safe, highly-reliable, low-cost and uniquely versatile propulsion...

  11. Advanced On Board Inert Gas Generation System (OBBIGS), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Valcor Engineering Corporation proposes to develop an advanced On Board Inert Gas Generation System, OBIGGS, for aircraft fuel tank inerting to prevent hazardous...

  12. Advanced 3D Object Identification System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Optra will build an Advanced 3D Object Identification System utilizing three or more high resolution imagers spaced around a launch platform. Data from each imager...

  13. The Vulcan Advanced Hybrid Manufacturing System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Made In Space is developing the The Vulcan Advanced Hybrid Manufacturing System (VULCAN) to address NASA's requirement to produce high-strength, high-precision...

  14. Advanced Vortex Hybrid Rocket Engine (AVHRE), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Orbital Technologies Corporation (ORBITEC) proposes to develop a unique Advanced Vortex Hybrid Rocket Engine (AVHRE) to achieve a highly-reliable, low-cost and...

  15. Acute Phase Hyperglycemia among Patients Hospitalized with Acute Coronary Syndrome: Prevalence and Prognostic Significance

    Directory of Open Access Journals (Sweden)

    Hameed Laftah Wanoose

    2011-03-01

    Full Text Available AbstractObjectives: Regardless of diabetes status, hyperglycemia on arrival for patients presenting with acute coronary syndrome, has been associated with adverse outcomes including death. The aim of this study is to look at the frequency and prognostic significance of acute phase hyperglycemia among patients attending the coronary care unit with acute coronary syndrome over the in-hospital admission days.Methods: The study included 287 consecutive patients in the Al- Faiha Hospital in Basrah (Southern Iraq during a one year period from December 2007 to November 2008. Patients were divided into two groups with respect to admission plasma glucose level regardless of their diabetes status (those with admission plasma glucose of <140 mg/dl (7.8 mmol/L and those equal to or more than that. Acute phase hyperglycemia was defined as a non-fasting glucose level equal to or above 140 mg/dl (7.8 mmol/L regardless of past history of diabetes.Results: Sixty one point seven percent (177 of patients were admitted with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences were found between both groups regarding the mean age, qualification, and smoking status, but males were predominant in both groups. A family history of diabetes, and hypertension, were more frequent in patients with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences between the two groups regarding past history of ischemic heart disease, stroke, lipid profile, troponin-I levels or type of acute coronary syndrome. Again heart failure was more common in the admission acute phase hyperglycemia group, but there was no difference regarding arrhythmia, stroke, or death. Using logistic regression with heart failure as the dependent variable we found that only the admission acute phase hyperglycemia (OR=2.1344, 95�0CI=1.0282-4.4307; p=0.0419 was independently associated with heart failure. While male gender, family history of diabetes mellitus, hypertension and

  16. The effects of betatron phase advances on beam-beam and its compensation in RHIC

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Y.; Fischer, W.; Gu, X.; Tepikian, S.; Trbojevic, D.

    2011-03-28

    In this article we perform simulation studies to investigate the effects of betatron phase advances between the beam-beam interaction points on half-integer resonance driving term, second order chromaticty and dynamic aperture in RHIC. The betatron phase advances are adjusted with artificial matrices inserted in the middle of arcs. The lattices for the 2011 RHIC polarized proton (p-p) run and 2010 RHIC Au-Au runs are used in this study. We also scan the betatron phase advances between IP8 and the electron lens for the proposed Blue ring lattice with head-on beam-beam compensation.

  17. Advanced Filtering Techniques Applied to Spaceflight, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — IST-Rolla developed two nonlinear filters for spacecraft orbit determination during the Phase I contract. The theta-D filter and the cost based filter, CBF, were...

  18. Advanced Technology Cloud Particle Probe for UAS, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In Phase II SPEC will design, fabricate and flight test a state-of-the-art combined cloud particle probe called the Hawkeye. Hawkeye is the culmination of two...

  19. Space-Ready Advanced Imaging System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In this Phase II effort Toyon will increase the state-of-the-art for video/image systems. This will include digital image compression algorithms as well as system...

  20. A Nanodroplet Processor for Advanced Microencapsulated Drug Formulations, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — During this Phase II program we propose to build on the key aspects of the nanodroplet encapsulation technology to demonstrate optimized formulation and...

  1. Efficiency improvement of nuclear power plant operation: the significant role of advanced nuclear fuel technologies

    International Nuclear Information System (INIS)

    Velde Van de, A.; Burtak, F.

    2001-01-01

    Due to the increased liberalisation of the power markets, nuclear power generation is being exposed to high cost reduction pressure. In this paper we highlight the role of advanced nuclear fuel technologies to reduce the fuel cycle costs and therefore increase the efficiency of nuclear power plant operation. The key factor is a more efficient utilisation of the fuel and present developments at Siemens are consequently directed at (i) further increase of batch average burnup, (ii) improvement of fuel reliability, (iii) enlargement of fuel operation margins and (iv) improvement of methods for fuel design and core analysis. As a result, the nuclear fuel cycle costs for a typical LWR have been reduced during the past decades by about US$ 35 million per year. The estimated impact of further burnup increases on the fuel cycle costs is expected to be an additional saving of US$10 - 15 million per year. Due to the fact that the fuel will operate closer to design limits, a careful approach is required when introducing advanced fuel features in reload quantities. Trust and co-operation between the fuel vendors and the utilities is a prerequisite for the common success. (authors)

  2. Advanced materials for future Phase II LHC collimators

    CERN Document Server

    Dallocchio, A; Arnau Izquierdo, G; Artoos, K

    2009-01-01

    Phase I collimators, equipped with Carbon-Carbon jaws, effectively met specifications for the early phase of LHC operation. However, the choice of carbon-based materials is expected to limit the nominal beam intensity mainly because of the high RF impedance and limited efficiency of the collimators. Moreover, C/C may be degraded by high radiation doses. To overcome these limitations, new Phase II secondary collimators will complement the existing system. Their extremely challenging requirements impose a thorough material investigation effort aiming at identifying novel materials combining very diverse properties. Relevant figures of merit have been identified to classify materials: Metal-diamonds composites look a promising choice as they combine good thermal, structural and stability properties. Molybdenum is interesting for its good thermal stability. Ceramics with non-conventional RF performances are also being evaluated. The challenges posed by the development and industrialization of these materials are ...

  3. Prognostic significance of s-phase fraction detected by antithymidine antibodies in epidermoid cervix carcinomas

    International Nuclear Information System (INIS)

    Zamulaeva, Irina A.; Podgorodnichenko, Vladimir K.; Guseva, Ludmila I.; Krikunova, Ludmila I.; Saenko, Alexander S.

    1996-01-01

    Purpose: To assess the predictive value of pretreatment proliferative activity of epidermoid cervix carcinoma cells with respect to short- and long-term results of radiotherapy. Methods and Materials: The proliferative activity of 25 epidermoid cervix carcinomas was evaluated as the immunofluorescent labelling index (LI) by rabbit antithymidine antibodies reacting specifically with single-stranded DNA of replication forks in S-phase cells. The short-term clinical outcome was estimated at 3-6 months after treatment by visual and palpatory examination. Three-year follow-up data were obtained through hospital charts and correspondence with referring physicians for only 19 patients. Results: There was no statistically significant association between LI and such conventional prognostic factors as clinical stage. The LI value of cervix carcinomas was significantly associated with complete regression at 3-6 months after radiotherapy and 3-year disease-free survival. Complete regression at 3-6 months was observed in 87.5% patients with fast proliferating tumors (LI > 7.0%), and only in 41.2% patients with slowly proliferating tumors (p = 0.03). Probability of 3-year disease-free survival was 85.7% in patients with fast proliferating tumors and 50.0% in those with slowly proliferating tumors (p = 0.05). Conclusions: The immunofluorescent LI of epidermoid cervix carcinoma is able to provide prognostic information on short-term tumor response to radiotherapy and disease-free survival

  4. The relationship between bioelectrical impedance phase angle and subjective global assessment in advanced colorectal cancer

    OpenAIRE

    Gupta, Digant; Lis, Christopher G; Dahlk, Sadie L; King, Jessica; Vashi, Pankaj G; Grutsch, James F; Lammersfeld, Carolyn A

    2008-01-01

    Abstract Background Bioelectrical Impedance (BIA) derived phase angle is increasingly being used as an objective indicator of nutritional status in advanced cancer. Subjective Global Assessment (SGA) is a subjective method of nutritional status. The objective of this study was to investigate the association between BIA derived phase angle and SGA in advanced colorectal cancer. Methods We evaluated a case series of 73 stages III and IV colorectal cancer patients. Patients were classified as ei...

  5. The effect of phase advance errors between interaction points on beam halos

    International Nuclear Information System (INIS)

    Chen, T.; Irwin, J.; Siemann, R.H.

    1995-01-01

    Phase advance errors between interaction points (IP) break the symmetry of multi-IP colliders. This symmetry breaking introduces new, lower order resonances which may chance the halo from the beam-beam interaction dramatically. In this paper, the mechanism of introducing new resonances is discussed. Simulation results showing the changes due to phase advance errors are presented. Simulation results are compared with experimental measurements at VEPP-2M

  6. Advanced worker protection system. Topical report, Phase I

    Energy Technology Data Exchange (ETDEWEB)

    Myers, J.

    1995-07-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project will result in the development of an Advanced Worker Protection System (AWPS). The AWPS will be built around a life support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack will be combined with advanced protective garments, advanced liquid cooling garment, respirator, communications, and support equipment to provide improved worker protection, simplified system, maintenance, and dramatically improve worker productivity through longer duration work cycles.

  7. Recent advances in two-phase flow numerics

    International Nuclear Information System (INIS)

    Mahaffy, J.H.; Macian, R.

    1997-01-01

    The authors review three topics in the broad field of numerical methods that may be of interest to individuals modeling two-phase flow in nuclear power plants. The first topic is iterative solution of linear equations created during the solution of finite volume equations. The second is numerical tracking of macroscopic liquid interfaces. The final area surveyed is the use of higher spatial difference techniques

  8. Recent advances in two-phase flow numerics

    Energy Technology Data Exchange (ETDEWEB)

    Mahaffy, J.H.; Macian, R. [Pennsylvania State Univ., University Park, PA (United States)

    1997-07-01

    The authors review three topics in the broad field of numerical methods that may be of interest to individuals modeling two-phase flow in nuclear power plants. The first topic is iterative solution of linear equations created during the solution of finite volume equations. The second is numerical tracking of macroscopic liquid interfaces. The final area surveyed is the use of higher spatial difference techniques.

  9. Advanced Pumps and Cold Plates for Two-Phase Cooling Loops, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced instruments used for earth science missions require improved cooling systems to remove heat from high power electronic components and maintain tight...

  10. Advanced computational model for three-phase slurry reactors

    International Nuclear Information System (INIS)

    Goodarz Ahmadi

    2001-10-01

    In the second year of the project, the Eulerian-Lagrangian formulation for analyzing three-phase slurry flows in a bubble column is further developed. The approach uses an Eulerian analysis of liquid flows in the bubble column, and makes use of the Lagrangian trajectory analysis for the bubbles and particle motions. An experimental set for studying a two-dimensional bubble column is also developed. The operation of the bubble column is being tested and diagnostic methodology for quantitative measurements is being developed. An Eulerian computational model for the flow condition in the two-dimensional bubble column is also being developed. The liquid and bubble motions are being analyzed and the results are being compared with the experimental setup. Solid-fluid mixture flows in ducts and passages at different angle of orientations were analyzed. The model predictions were compared with the experimental data and good agreement was found. Gravity chute flows of solid-liquid mixtures is also being studied. Further progress was also made in developing a thermodynamically consistent model for multiphase slurry flows with and without chemical reaction in a state of turbulent motion. The balance laws are obtained and the constitutive laws are being developed. Progress was also made in measuring concentration and velocity of particles of different sizes near a wall in a duct flow. The technique of Phase-Doppler anemometry was used in these studies. The general objective of this project is to provide the needed fundamental understanding of three-phase slurry reactors in Fischer-Tropsch (F-T) liquid fuel synthesis. The other main goal is to develop a computational capability for predicting the transport and processing of three-phase coal slurries. The specific objectives are: (1) To develop a thermodynamically consistent rate-dependent anisotropic model for multiphase slurry flows with and without chemical reaction for application to coal liquefaction. Also establish the

  11. Phase 1 Development Testing of the Advanced Manufacturing Demonstrator Engine

    Science.gov (United States)

    Case, Nicholas L.; Eddleman, David E.; Calvert, Marty R.; Bullard, David B.; Martin, Michael A.; Wall, Thomas R.

    2016-01-01

    The Additive Manufacturing Development Breadboard Engine (BBE) is a pressure-fed liquid oxygen/pump-fed liquid hydrogen (LOX/LH2) expander cycle engine that was built and operated by NASA at Marshall Space Flight Center's East Test Area. The breadboard engine was conceived as a technology demonstrator for the additive manufacturing technologies for an advanced upper stage prototype engine. The components tested on the breadboard engine included an ablative chamber, injector, main fuel valve, turbine bypass valve, a main oxidizer valve, a mixer and the fuel turbopump. All parts minus the ablative chamber were additively manufactured. The BBE was successfully hot fire tested seven times. Data collected from the test series will be used for follow on demonstration tests with a liquid oxygen turbopump and a regeneratively cooled chamber and nozzle.

  12. Phase III Advanced Anodes and Cathodes Utilized in Energy Efficient Aluminum Production Cells; FINAL

    International Nuclear Information System (INIS)

    Christini, R.A.; Dawless, R.K.; Ray, S.P.; Weirauch, D.A. Jr.

    2001-01-01

    During Phase I of the present program, Alcoa developed a commercial cell concept that has been estimated to save 30% of the energy required for aluminum smelting. Phase ii involved the construction of a pilot facility and operation of two pilots. Phase iii of the Advanced Anodes and Cathodes Program was aimed at bench experiments to permit the resolution of certain questions to be followed by three pilot cells. All of the milestones related to materials, in particular metal purity, were attained with distinct improvements over work in previous phases of the program. NiO additions to the ceramic phase and Ag additions to the Cu metal phase of the cermet improved corrosion resistance sufficiently that the bench scale pencil anodes met the purity milestones. Some excellent metal purity results have been obtained with anodes of the following composition: Further improvements in anode material composition appear to be dependent on a better understanding of oxide solubilities in molten cryolite. For that reason, work was commissioned with an outside consultant to model the MeO - cryolite systems. That work has led to a better understanding of which oxides can be used to substitute into the NiO-Fe2O3 ceramic phase to stabilize the ferrites and reduce their solubility in molten cryolite. An extensive number of vertical plate bench electrolysis cells were run to try to find conditions where high current efficiencies could be attained. TiB2-G plates were very inconsistent and led to poor wetting and drainage. Pure TiB2 did produce good current efficiencies at small overlaps (shadowing) between the anodes and cathodes. This bench work with vertical plate anodes and cathodes reinforced the importance of good cathode wetting to attain high current efficiencies. Because of those conclusions, new wetting work was commissioned and became a major component of the research during the third year of Phase III. While significant progress was made in several areas, much work needs to be

  13. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma

    International Nuclear Information System (INIS)

    Hoyer, Morten; Roed, Henrik; Sengelov, Lisa; Traberg, Anders; Ohlhuis, Lars; Pedersen, Jorgen; Nellemann, Hanne; Kiil Berthelsen, Anne; Eberholst, Frey; Engelholm, Svend Aage; Maase, Hans von der

    2005-01-01

    Background and purpose: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. Patients and methods: Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days. Results: Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. Conclusions: SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma

  14. Federal Radiological Monitoring and Assessment Center advanced part phase response actions

    International Nuclear Information System (INIS)

    Hurley, B.

    1997-01-01

    Federal Radiological Monitoring and Assessment Center (FRMAC) response actions are carried out in Advance Party and Main Party phases of deployment. Response activities are initiated by a FRMAC Home Team prior to and during Advance Party deployment, with Home Team support continuing until the FRMAC Main Party is fully deployed. Upon arrival at the incident scene, the Advance Party establishes communications with other federal, state, and local response organizations, Following an Advance Party Meeting with these response organizations, FRMAC begins formulation of an initial monitoring and sampling plan, in coordination with the jurisdictional state and the Lead Federal Agency, and initiates detailed logistical arrangements for Main Party deployment and operations

  15. Advanced computational model for three-phase slurry reactors

    International Nuclear Information System (INIS)

    Goodarz Ahmadi

    2000-11-01

    In the first year of the project, solid-fluid mixture flows in ducts and passages at different angle of orientations were analyzed. The model predictions are compared with the experimental data and good agreement was found. Progress was also made in analyzing the gravity chute flows of solid-liquid mixtures. An Eulerian-Lagrangian formulation for analyzing three-phase slurry flows in a bubble column is being developed. The approach uses an Eulerian analysis of gas liquid flows in the bubble column, and makes use of the Lagrangian particle tracking procedure to analyze the particle motions. Progress was also made in developing a rate dependent thermodynamically consistent model for multiphase slurry flows in a state of turbulent motion. The new model includes the effect of phasic interactions and leads to anisotropic effective phasic stress tensors. Progress was also made in measuring concentration and velocity of particles of different sizes near a wall in a duct flow. The formulation of a thermodynamically consistent model for chemically active multiphase solid-fluid flows in a turbulent state of motion was also initiated. The general objective of this project is to provide the needed fundamental understanding of three-phase slurry reactors in Fischer-Tropsch (F-T) liquid fuel synthesis. The other main goal is to develop a computational capability for predicting the transport and processing of three-phase coal slurries. The specific objectives are: (1) To develop a thermodynamically consistent rate-dependent anisotropic model for multiphase slurry flows with and without chemical reaction for application to coal liquefaction. Also to establish the material parameters of the model. (2) To provide experimental data for phasic fluctuation and mean velocities, as well as the solid volume fraction in the shear flow devices. (3) To develop an accurate computational capability incorporating the new rate-dependent and anisotropic model for analyzing reacting and

  16. Ullage Compatible Optical Sensor for Monitoring Safety-Significant Malfunctions, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The tasks of this Phase I proposal are designed to establish the feasibility of an optical sensor for real-time, in situ monitoring of the ullage environment of an...

  17. A Nanotube Surface Reinforced Graphite Fiber Exhibiting Significantly Enhanced Properties, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The completed Phase I work was directed at the application of nanotechnology to graphite/epoxy composites. A novel approach to the application of the nanotubes onto...

  18. Advanced nonlinear control of three phase series active power filter

    Directory of Open Access Journals (Sweden)

    Abouelmahjoub Y.

    2014-01-01

    Full Text Available The problem of controlling three-phase series active power filter (TPSAPF is addressed in this paper in presence of the perturbations in the voltages of the electrical supply network. The control objective of the TPSAPF is twofold: (i compensation of all voltage perturbations (voltage harmonics, voltage unbalance and voltage sags, (ii regulation of the DC bus voltage of the inverter. A controller formed by two nonlinear regulators is designed, using the Backstepping technique, to provide the above compensation. The regulation of the DC bus voltage of the inverter is ensured by the use of a diode bridge rectifier which its output is in parallel with the DC bus capacitor. The Analysis of controller performances is illustrated by numerical simulation in Matlab/Simulink environment.

  19. ADVANCED COMPUTATIONAL MODEL FOR THREE-PHASE SLURRY REACTORS

    International Nuclear Information System (INIS)

    Ahmadi, Goodarz

    2004-01-01

    In this project, an Eulerian-Lagrangian formulation for analyzing three-phase slurry flows in a bubble column was developed. The approach used an Eulerian analysis of liquid flows in the bubble column, and made use of the Lagrangian trajectory analysis for the bubbles and particle motions. The bubble-bubble and particle-particle collisions are included the model. The model predictions are compared with the experimental data and good agreement was found An experimental setup for studying two-dimensional bubble columns was developed. The multiphase flow conditions in the bubble column were measured using optical image processing and Particle Image Velocimetry techniques (PIV). A simple shear flow device for bubble motion in a constant shear flow field was also developed. The flow conditions in simple shear flow device were studied using PIV method. Concentration and velocity of particles of different sizes near a wall in a duct flow was also measured. The technique of Phase-Doppler anemometry was used in these studies. An Eulerian volume of fluid (VOF) computational model for the flow condition in the two-dimensional bubble column was also developed. The liquid and bubble motions were analyzed and the results were compared with observed flow patterns in the experimental setup. Solid-fluid mixture flows in ducts and passages at different angle of orientations were also analyzed. The model predictions were compared with the experimental data and good agreement was found. Gravity chute flows of solid-liquid mixtures were also studied. The simulation results were compared with the experimental data and discussed A thermodynamically consistent model for multiphase slurry flows with and without chemical reaction in a state of turbulent motion was developed. The balance laws were obtained and the constitutive laws established

  20. Asthma-COPD overlap syndrome: recent advances in diagnostic criteria and prognostic significance.

    Science.gov (United States)

    Sorino, Claudio; Scichilone, Nicola; D'Amato, Maria; Patella, Vincenzo; DI Marco, Fabiano

    2017-06-01

    The term asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has been proposed for individuals with features of both asthma and COPD. Several attempts have been done to define ACOS on the basis of medical history, symptoms, and functional findings. The main diagnostic criteria include airflow obstruction with a strong although incomplete reversibility to bronchodilation tests, a significant exposure to cigarette or biomass smoke, and a history of atopy or asthma. Additional diagnostic elements include eosinophilic airway and systemic inflammation, a good response to corticosteroid treatment, and a high concentration of exhaled nitric oxide. ACOS should be distinguished from asthma with not fully reversible bronchial obstruction due to airway remodeling, thus the lack of smoking exposure should exclude the diagnosis of ACOS. In patients without a documented history of asthma before 40 years of age, an increase in FEV1 after bronchodilator >400 mL should be required to diagnose ACOS. ACOS has been found to be associated with impaired physical performance, functional ability, and health-related quality of life. The prevalence of ACOS increases with aging, then it is relatively stable in elderly individuals (>65 years). Long-term mortality of subjects with ACOS is similar to COPD, and worse than asthma and healthy controls. Future research is still needed to improve the understanding and management of ACOS.

  1. Interaction between FOXO1A-209 Genotype and Tea Drinking is Significantly Associated with Reduced Mortality at Advanced Ages

    DEFF Research Database (Denmark)

    Zeng, Yi; Chen, Huashuai; Ni, Ting

    2016-01-01

    Based on the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality...... at advanced ages. Such significant association is replicated in two independent Han Chinese CLHLS cohorts (p =0.028-0.048 in the discovery and replication cohorts, and p =0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers...... of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably...

  2. Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease Patient with Significant Tremor and Comorbid Depression

    Directory of Open Access Journals (Sweden)

    Amar S. Patel

    2017-04-01

    Full Text Available Clinical Vignette: A 67-year-old female with advanced Parkinson's disease (PD, medically refractory tremor, and a history of significant depression presents for evaluation of deep brain stimulation (DBS candidacy.  Clinical Dilemma: Traditionally, stimulation of the subthalamic nucleus (STN has been the preferred target for patients with significant PD tremor. However, STN stimulation is avoided in patients with a significant pre-surgical history of mood disorder.  Clinical Solution: Bilateral DBS of the globus pallidus interna led to significant short term improvement in PD motor symptoms, including significant tremor reduction.  Gap in Knowledge: There is insufficient evidence to support or refute clinicians' traditional preference for STN stimulation in treating refractory PD tremor. Similarly, the available evidence for risk of worsening depression and/or suicidality after STN DBS is mixed. Both questions require further clarification to guide patient and clinician decision-making.

  3. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    Science.gov (United States)

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  4. Significance of phase-display technique for diagnosis of WPW-Syndrome

    International Nuclear Information System (INIS)

    Mester, J.; Mate, E.; Marosi, G.; Csernay, L.

    1985-01-01

    28 patients with WPW-syndrome were investigated by nuclear cardiology. Phase-display techniques were capable of visualizing and localizing ventricular preexcitations. The prematurely contraction ventricle was diagnosed in 81% of the cases concordant to the results of 12-channel ECG-technique. The control group consisted of 13 LGL-patients and revealed 3 false positives resulting in a specificity of 77%. The results were checked with respect to reproducibility. Additional projections increased the sensitivity of the method. (orig.) [de

  5. Harvesting yeast (Saccharomyces cerevisiae) at different physiological phases significantly affects its functionality in bread dough fermentation.

    Science.gov (United States)

    Rezaei, Mohammad N; Dornez, Emmie; Jacobs, Pieter; Parsi, Anali; Verstrepen, Kevin J; Courtin, Christophe M

    2014-05-01

    Fermentation of sugars into CO2, ethanol and secondary metabolites by baker's yeast (Saccharomyces cerevisiae) during bread making leads to leavening of dough and changes in dough rheology. The aim of this study was to increase our understanding of the impact of yeast on dough related aspects by investigating the effect of harvesting yeast at seven different points of the growth profile on its fermentation performance, metabolite production, and the effect on critical dough fermentation parameters, such as gas retention potential. The yeast cells harvested during the diauxic shift and post-diauxic growth phase showed a higher fermentation rate and, consequently, higher maximum dough height than yeast cells harvested in the exponential or stationary growth phase. The results further demonstrate that the onset of CO2 loss from fermenting dough is correlated with the fermentation rate of yeast, but not with the amount of CO2 that accumulated up to the onset point. Analysis of the yeast metabolites produced in dough yielded a possible explanation for this observation, as they are produced in different levels depending on physiological phase and in concentrations that can influence dough matrix properties. Together, our results demonstrate a strong effect of yeast physiology at the time of harvest on subsequent dough fermentation performance, and hint at an important role of yeast metabolites on the subsequent gas holding capacity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT- CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, R.

    2013-02-26

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  7. Advanced direct liquefaction concepts for PETC generic units. Final report, Phase I

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-03-01

    The Advanced Concepts for Direct Coal Liquefaction program was initiated by the Department of Energy in 1991 to develop technologies that could significantly reduce the cost of producing liquid fuels by the direct liquefaction of coal. The advanced 2-stage liquefaction technology that was developed at Wilsonville over the past 10 years has contributed significantly toward decreasing the cost of producing liquids from coal to about $33/bbl. It remains, however, the objective of DOE to further reduce this cost to a level more competitive with petroleum based products. This project, among others, was initiated to investigate various alternative approaches to develop technologies that might ultimately lead to a 25 % reduction in cost of product. In this project a number of novel concepts were investigated, either individually or in a coupled configuration that had the potential to contribute toward meeting the DOE goal. The concepts included mature technologies or ones closely related to them, such as coal cleaning by oil agglomeration, fluid coking and distillate hydrotreating and dewaxing. Other approaches that were either embryonic or less developed were chemical pretreatment of coal to remove oxygen, and dispersed catalyst development for application in the 2-stage liquefaction process. This report presents the results of this project. It is arranged in four sections which were prepared by participating organizations responsible for that phase of the project. A summary of the overall project and the principal results are given in this section. First, however, an overview of the process economics and the process concepts that were developed during the course of this program is presented.

  8. Advanced induction machine model in phase coordinates for wind turbine applications

    DEFF Research Database (Denmark)

    Fajardo, L.A.; Iov, F.; Hansen, Anca Daniela

    2007-01-01

    In this paper an advanced phase coordinates squirrel cage induction machine model with time varying electrical parameters affected by magnetic saturation and rotor deep bar effects, is presented. The model uses standard data sheet for characterization of the electrical parameters, it is developed...

  9. Phase I study of 4-demethoxydaunorubicin by oral route in patients with advanced cancer

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Andersen, E; Elbaek, K

    1988-01-01

    In a phase I trial 4-demethoxydaunorubicin (4-dm DNR) was administered as oral capsules once a week to 51 adults with advanced mainly gastrointestinal solid tumors. No fatal toxicity was observed at doses up to 25.0 mg/m2. Dose-limiting granulocytopenia and non-hematologic toxicity developed...

  10. Advancement and Application of Multi-Phase CFD Modeling to High Speed Supercavitating Flows

    Science.gov (United States)

    2013-08-13

    October 2008 - December 2013 4. TITLE AND SUBTITLE Advancement and Application of Multi-Phase CFD Modeling to High Speed Supercavitating Flows...influence cavity hysteresis behavior. These observations are used to guide improved supercavitating -vehicle analyses including numerical predictions...experiments, and modeling 15. SUBJECT TERMS supercavitation , computational fluid dynamics, multiphase flow 16. SECURITY CLASSIFICATION OF: a

  11. Advanced Communication and Control for Distributed Energy Resource Integration: Phase 2 Scientific Report

    Energy Technology Data Exchange (ETDEWEB)

    BPL Global

    2008-09-30

    The objective of this research project is to demonstrate sensing, communication, information and control technologies to achieve a seamless integration of multivendor distributed energy resource (DER) units at aggregation levels that meet individual user requirements for facility operations (residential, commercial, industrial, manufacturing, etc.) and further serve as resource options for electric and natural gas utilities. The fully demonstrated DER aggregation system with embodiment of communication and control technologies will lead to real-time, interactive, customer-managed service networks to achieve greater customer value. Work on this Advanced Communication and Control Project (ACCP) consists of a two-phase approach for an integrated demonstration of communication and control technologies to achieve a seamless integration of DER units to reach progressive levels of aggregated power output. Phase I involved design and proof-of-design, and Phase II involves real-world demonstration of the Phase I design architecture. The scope of work for Phase II of this ACCP involves demonstrating the Phase I design architecture in large scale real-world settings while integrating with the operations of one or more electricity supplier feeder lines. The communication and control architectures for integrated demonstration shall encompass combinations of software and hardware components, including: sensors, data acquisition and communication systems, remote monitoring systems, metering (interval revenue, real-time), local and wide area networks, Web-based systems, smart controls, energy management/information systems with control and automation of building energy loads, and demand-response management with integration of real-time market pricing. For Phase II, BPL Global shall demonstrate the Phase I design for integrating and controlling the operation of more than 10 DER units, dispersed at various locations in one or more Independent System Operator (ISO) Control Areas, at

  12. Investor Outlook: Significance of the Positive LCA2 Gene Therapy Phase III Results.

    Science.gov (United States)

    Schimmer, Joshua; Breazzano, Steven

    2015-12-01

    Spark Therapeutics recently reported positive phase III results for SPK-RPE65 targeting the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders), marking an important inflection point for the field of gene therapy. The results highlight the ability to successfully design and execute a randomized trial of a gene therapy and also reinforce the potentially predictive nature of early preclinical and clinical data. The results are expected to pave the way for the first approved gene therapy product in the United States and should sustain investor interest and confidence in gene therapy for many approaches, including retina targeting and beyond.

  13. Ullage Compatible Optical Sensor for Monitoring Safety Significant Malfunctions, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Significant emphasis has been placed on aircraft fuel tank safety following the TWA Flight 800 accident in July 1996. Upon investigation, the National Transportation...

  14. Endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma: Is it a significant prognostic factor?

    Science.gov (United States)

    Shin, Hae Jin; Moon, Hee Seok; Kang, Sun Hyung; Sung, Jae Kyu; Jeong, Hyun Yong; Kim, Seok Hyun; Lee, Byung Seok; Kim, Ju Seok; Yun, Gee Young

    2017-12-01

    The purpose of this study was to evaluate the prognostic impact of endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma.This retrospective study was based on medical records from a single tertiary medical center. The records of 317 patients with esophageal squamous cell carcinoma treated with surgery or definitive chemoradiotherapy (CRT) between January 2009 and March 2016 were reviewed. Finally, we retrieved the data on 168 consecutive patients. These 168 patients were divided into 2 groups based on their endoscopic traversability findings: Group A (the endoscope traversable group), and Group B (the endoscope non-traversable group). We then retrospectively compared the clinical characteristics of these 2 groups.The endoscope non-traversable group (Group B) revealed an advanced clinical stage, a poor Eastern Cooperative Oncology Group (ECOG) score, a lower serum albumin level, a higher rate of requirement for esophageal stent insertion and definitive CRT as initial treatment than the endoscope traversable group (Group A). Patients with endoscope traversable cancer showed a significantly higher 3-year overall survival and 3-year relapse-free survival than patients who were endoscope non-traversable (53.8% vs 17.3%, P squamous cell carcinoma treated with definitive CRT, the serum albumin level squamous cell carcinoma treated with definitive CRT is a significant prognostic factor. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  15. Integrated Advanced Monopropellant CMC Thruster / Thermal Stand-Off Assembly, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — High performance non-toxic monopropellants offer significant benefits relative to the current state-of-the-art. The benefits of these advanced monopropellants (AMP)...

  16. Life prediction methodology for ceramic components of advanced heat engines. Phase 1: Volume 1, Final report

    Energy Technology Data Exchange (ETDEWEB)

    Cuccio, J.C.; Brehm, P.; Fang, H.T. [Allied-Signal Aerospace Co., Phoenix, AZ (United States). Garrett Engine Div.] [and others

    1995-03-01

    Emphasis of this program is to develop and demonstrate ceramics life prediction methods, including fast fracture, stress rupture, creep, oxidation, and nondestructive evaluation. Significant advancements were made in these methods and their predictive capabilities successfully demonstrated.

  17. Innovative grinding wheel design for cost-effective machining of advanced ceramics. Phase I, final report

    Energy Technology Data Exchange (ETDEWEB)

    Licht, R.H.; Ramanath, S.; Simpson, M.; Lilley, E.

    1996-02-01

    Norton Company successfully completed the 16-month Phase I technical effort to define requirements, design, develop, and evaluate a next-generation grinding wheel for cost-effective cylindrical grinding of advanced ceramics. This program was a cooperative effort involving three Norton groups representing a superabrasive grinding wheel manufacturer, a diamond film manufacturing division and a ceramic research center. The program was divided into two technical tasks, Task 1, Analysis of Required Grinding Wheel Characteristics, and Task 2, Design and Prototype Development. In Task 1 we performed a parallel path approach with Superabrasive metal-bond development and the higher technical risk, CVD diamond wheel development. For the Superabrasive approach, Task 1 included bond wear and strength tests to engineer bond-wear characteristics. This task culminated in a small-wheel screening test plunge grinding sialon disks. In Task 2, an improved Superabrasive metal-bond specification for low-cost machining of ceramics in external cylindrical grinding mode was identified. The experimental wheel successfully ground three types of advanced ceramics without the need for wheel dressing. The spindle power consumed by this wheel during test grinding of NC-520 sialon is as much as to 30% lower compared to a standard resin bonded wheel with 100 diamond concentration. The wheel wear with this improved metal bond was an order of magnitude lower than the resin-bonded wheel, which would significantly reduce ceramic grinding costs through fewer wheel changes for retruing and replacements. Evaluation of ceramic specimens from both Tasks 1 and 2 tests for all three ceramic materials did not show evidence of unusual grinding damage. The novel CVD-diamond-wheel approach was incorporated in this program as part of Task 1. The important factors affecting the grinding performance of diamond wheels made by CVD coating preforms were determined.

  18. Listeriosis in animals, its public health significance (food-borne zoonosis) and advances in diagnosis and control: a comprehensive review.

    Science.gov (United States)

    Dhama, Kuldeep; Karthik, Kumaragurubaran; Tiwari, Ruchi; Shabbir, Muhammad Zubair; Barbuddhe, Sukhadeo; Malik, Satya Veer Singh; Singh, Raj Kumar

    2015-01-01

    Listeriosis is an infectious and fatal disease of animals, birds, fish, crustaceans and humans. It is an important food-borne zoonosis caused by Listeria monocytogenes, an intracellular pathogen with unique potential to spread from cell to cell, thereby crossing blood-brain, intestinal and placental barriers. The organism possesses a pile of virulence factors that help to infect the host and evade from host immune machinery. Though disease occurrence is sporadic throughout the world, it can result in severe damage during an outbreak. Listeriosis is characterized by septicaemia, encephalitis, meningitis, meningoencephalitis, abortion, stillbirth, perinatal infections and gastroenteritis with the incubation period varying with the form of infection. L. monocytogenes has been isolated worldwide from humans, animals, poultry, environmental sources like soil, river, decaying plants, and food sources like milk, meat and their products, seafood and vegetables. Since appropriate vaccines are not available and infection is mainly transmitted through foods in humans and animals, hygienic practices can prevent its spread. The present review describes etiology, epidemiology, transmission, clinical signs, post-mortem lesions, pathogenesis, public health significance, and advances in diagnosis, vaccines and treatment of this disease. Special attention has been given to novel as well as prospective emerging therapies that include bacteriophage and cytokine therapy, avian egg yolk antibodies and herbal therapy. Various vaccines, including advances in recombinant and DNA vaccines and their modes of eliciting immune response, are also discussed. Due focus has also been given regarding appropriate prevention and control strategies to be adapted for better management of this zoonotic disease.

  19. A phase I study of vorinostat in combination with bortezomib in patients with advanced malignancies.

    Science.gov (United States)

    Schelman, William R; Traynor, Anne M; Holen, Kyle D; Kolesar, Jill M; Attia, Steven; Hoang, Tien; Eickhoff, Jens; Jiang, Zhisheng; Alberti, Dona; Marnocha, Rebecca; Reid, Joel M; Ames, Matthew M; McGovern, Renee M; Espinoza-Delgado, Igor; Wright, John J; Wilding, George; Bailey, Howard H

    2013-12-01

    A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors. Patients received vorinostat orally once daily on days 1-14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m(2)). Bortezomib dosing was increased using a standard phase I dose-escalation schema. PKs were evaluated during cycle 1. Twenty-three patients received 57 cycles of treatment on four dose levels ranging from bortezomib 0.7 mg/m(2) to 1.5 mg/m(2). The MTD was established at vorinostat 400 mg daily and bortezomib 1.3 mg/m(2). DLTs consisted of grade 3 fatigue in three patients (1 mg/m(2),1.3 mg/m(2) and 1.5 mg/m(2)) and grade 3 hyponatremia in one patient (1.5 mg/m(2)). The most common grade 1/2 toxicities included nausea (60.9%), fatigue (34.8%), diaphoresis (34.8%), anorexia (30.4%) and constipation (26.1%). Objective partial responses were observed in one patient with NSCLC and in one patient with treatment-refractory soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however, the Cmax and AUC of the acid metabolite were significantly increased on day 2 compared with day 1. This combination was generally well-tolerated at doses that achieved clinical benefit. The MTD was established at vorinostat 400 mg daily × 14 days and bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21-day cycle.

  20. Advanced gastric cancer. The findings of delayed phase dynamic CT and radiologic-histopathologic correlation

    International Nuclear Information System (INIS)

    Monzawa, Shuichi; Omata, Kosaku; Nakazima, Hiroto; Yokosuka, Noriko; Ito, Atuko; Araki, Tsutomu

    2000-01-01

    The aim of this study was to describe delayed phase dynamic CT findings of advanced (T2-T4) gastric cancer and to correlate with histopathologic findings. Quadruple phase dynamic CT including delayed imaging taken five minutes after the start of injection of contrast material was performed in 43 patients with 45 advanced gastric cancer and 20 control subjects with no gastric lesions. On delayed phase CT scans, the attenuation of the gastric wall was equal to or lower than that of the liver parenchyma in the control subjects, therefore, the presence of higher attenuation in the gastric wall was considered to be abnormal and defined as delayed enhancement. Histopathologic findings in the tumors showing delayed enhancement were compared with those in the tumors without this feature. Delayed enhancement was seen in 26 (57%) of the 45 tumors. Eleven of 25 differentiated-type tumors and 15 of 20 undifferentiated-type tumors showed delayed enhancement (p<.05). Delayed enhancement was seen in one of five medullary type tumors, in 11 of 25 intermediate-type tumors, and in 14 of 15 scirrhous-type tumors (p<.005). Delayed enhancement was frequently seen in the tumors with abundant fibrous tissue stroma. Delayed phase dynamic CT may be useful for the characterization of advanced gastric cancer. (author)

  1. Application of an advanced cost model in the different design phases of an offshore wind turbine

    Energy Technology Data Exchange (ETDEWEB)

    Hendriks, H.B.; Lindenburg, C.; Kooijman, H.J.T.; Bulder, B.H. [ECN Wind, Petten (Netherlands); Bozelie, J.; Madsen, J.B. [NEG Micon Holland, Rhenen (Netherlands); Halfschepel, R. [Van Oord ACZ, Gorinchem (Netherlands); Molenaar, W. [Ballast Nedam, Amstelveen (Netherlands); Van den Berg, R. [LM Glasfiber Holland, Heerhugowaard (Netherlands); Zaaijer, M. [TU-Delft, Delft (Netherlands)

    2001-09-01

    The goal of the Dutch Offshore Wind Energy Converter (DOWEC) consortium is to develop concepts and technology in order to make large scale offshore wind energy economically feasible. The overall DOWEC development comprises of the design, the construction, and the prototype testing. Onshore testing of a 3 MW research and development prototype is scheduled for the end of 2002. The DOWEC Concept Study aims at the choice of the optimal wind turbine concept. The wind turbine will not be treated as an isolated system. Designs of different wind turbine concepts will be evaluated as an integral part of the complete large-scale offshore wind farm. All significant properties like the structural loads, the power performance, the system reliability, the costs of the electric infrastructure, maintenance costs and installation costs is determined for the optimised designs. A quantitative ranking is then based on the cost of energy generated. Furthermore qualitative criteria like development risk and market potential will be taken into consideration when finalising the choice of concept. An advanced cost model is being developed to facilitate the above evaluation on basis of estimated energy generating costs for each concept. The same methodology will also be used in the system and detail design phase. This paper describes the DOWEC project in general, focusing at the cost modelling aspects including some preliminary results. 4 refs.

  2. Josephson phase qubit circuit for the evaluation of advanced tunnel barrier materials

    Energy Technology Data Exchange (ETDEWEB)

    Kline, Jeffrey S; Oh, Seongshik; Pappas, David P [National Institute of Standards and Technology, Boulder, CO 80305 (United States); Wang Haohua; Martinis, John M [Department of Physics, University of California, Santa Barbara, CA 93106 (United States)], E-mail: klinej@nist.gov

    2009-01-15

    We have found that crystalline Josephson junctions have problems with the control of critical current density that decrease the circuit yield. We present a superconducting quantum bit circuit designed to accommodate a factor of five variation in critical current density from one fabrication run to the next. The new design enables the evaluation of advanced tunnel barrier materials for superconducting quantum bits. Using this circuit design, we compare the performance of Josephson phase qubits fabricated with MgO and Al{sub 2}O{sub 3} advanced crystalline tunnel barriers to AlO{sub x} amorphous tunnel barrier qubits.

  3. GxE Interactions Between FOXO Genotypes and Tea Drinking Significantly Affect Cognitive Disability at Advanced Ages in China

    DEFF Research Database (Denmark)

    Zeng, Yi; Chen, Huashuai; Ni, Ting

    2015-01-01

    Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability...... at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around...... age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health...

  4. Combined fluorescence and phase contrast imaging at the Advanced Photon Source

    International Nuclear Information System (INIS)

    Hornberger, B.; Feser, M.; Jacobsen, C.; Vogt, S.; Legnini, D.; Paterson, D.; Rehak, P.; DeGeronimo, G.; Palmer, B.M.; Experimental Facilities Division; State Univ. of New York at Stony Brook Univ.; BNL; Univ. of Vermont

    2006-01-01

    X-ray fluorescence microprobes excel at detecting and quantifying trace metals in biological and environmental science samples, but typically do not detect low Z elements such as carbon and nitrogen. Therefore, it is hard to put the trace metals into context with their natural environment. We are implementing phase contrast capabilities with a segmented detector into several microprobes at the Advanced Photon Source (APS) to address this problem. Qualitative differential phase contrast images from a modified soft x-ray detector already provide very useful information for general users. We are also implementing a quantitative method to recover the absolute phase shift by Fourier filtering detector images. New detectors are under development which are optimized for the signal levels present at the APS. In this paper, we concentrate on fundamental signal to noise considerations comparing absorption and differential phase contrast

  5. Dual-polarization interference microscopy for advanced quantification of phase associated with the image field.

    Science.gov (United States)

    Bouchal, Petr; Chmelík, Radim; Bouchal, Zdeněk

    2018-02-01

    A new concept of dual-polarization spatial light interference microscopy (DPSLIM) is proposed and demonstrated experimentally. The method works with two orthogonally polarized modes in which signal and reference waves are combined to realize the polarization-sensitive phase-shifting, thus allowing advanced reconstruction of the phase associated with the image field. The image phase is reconstructed directly from four polarization encoded interference records by a single step processing. This is a progress compared with common methods, in which the phase of the image field is reconstructed using the optical path difference and the amplitudes of interfering waves, which are calculated in multiple-step processing of the records. The DPSLIM is implemented in a common-path configuration using a spatial light modulator, which is connected to a commercial microscope Nikon E200. The optical performance of the method is demonstrated in experiments using both polystyrene microspheres and live LW13K2 cells.

  6. A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

    Science.gov (United States)

    Kjorstad, K; Harris, A; Bertelsen, K; Slevin, M; Schultz, H; Hellman, K; Janssens, N; Martin, A; Canetta, R

    1992-03-01

    A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

  7. Prognostic significance of mediastinal {sup 18}F-FDG uptake in PET/CT in advanced ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bats, Anne-Sophie; Lecuru, Fabrice [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, INSERM UMR-S 747, Paris (France); Hugonnet, Florent; Faraggi, Marc [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France); Huchon, Cyrille [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Bensaid, Cherazade [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Pierquet-Ghazzar, Nadia [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France)

    2012-03-15

    To evaluate the prognostic significance of increased mediastinal {sup 18}F-FDG uptake in PET/CT for the staging of advanced ovarian cancer. We retrospectively evaluated patients managed for FIGO stage III/IV ovarian cancer between 1 January 2006 and 1 June 2009. Patients were included if they had undergone {sup 18}F-FDG PET/CT and surgery for initial staging. Exclusion criteria were age younger than 18 years, inability to undergo general anaesthesia, recurrent ovarian cancer, and borderline or nonepithelial malignancy. Whole-body PET/CT was performed after intravenous {sup 18}F-FDG injection. The location of abnormal hot spots and {sup 18}F-FDG maximal standard uptake values (SUV{sub max}) were recorded. We compared the complete cytoreduction and survival rates in groups defined based on mediastinal {sup 18}F-FDG uptake and SUV{sub max} values. Kaplan-Meier curves of overall survival and disease-free survival were compared using the log-rank test. Hazard ratios with their 95% confidence intervals were computed. Adjusted hazard ratios were obtained using a multivariate Cox model. We included 53 patients, of whom 17 (32%) had increased mediastinal {sup 18}F-FDG uptake. Complete cytoreduction was achieved in 14 (87.5%) of the 16 patients managed with primary surgery and in 21 (75%) of the 28 patients managed with interval surgery. Complete cytoreduction was achieved significantly more often among patients without increased mediastinal {sup 18}F-FDG uptake (80.6% vs. 35.3%; p = 0.001). Disease-free survival was comparable between the two groups. By univariate analysis, overall mortality was significantly higher among patients with increased mediastinal {sup 18}F-FDG uptake (hazard ratio 5.70, 95% confidence interval 1.74-18.6). The only factor significantly associated with overall survival by multivariate analysis was complete cytoreduction (adjusted hazard ratio 0.24, 95% confidence interval 0.07-0.89). Increased mediastinal {sup 18}F-FDG uptake was common in patients

  8. Combination of light and melatonin time cues for phase advancing the human circadian clock.

    Science.gov (United States)

    Burke, Tina M; Markwald, Rachel R; Chinoy, Evan D; Snider, Jesse A; Bessman, Sara C; Jung, Christopher M; Wright, Kenneth P

    2013-11-01

    Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. Sleep and chronobiology laboratory environment free of time cues. Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD). Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

  9. UTILITY ADVANCED TURBINE SYSTEMS (ATS) TECHNOLOGY READINESS TESTING: PHASE 3R

    Energy Technology Data Exchange (ETDEWEB)

    None

    1999-09-01

    The overall objective of the Advanced Turbine System (ATS) Phase 3 Cooperative Agreement between GE and the US Department of Energy (DOE) is the development of the GE 7H and 9H combined cycle power systems. The major effort will be expended on detail design. Validation of critical components and technologies will be performed, including: hot gas path component testing, sub-scale compressor testing, steam purity test trials, and rotational heat transfer confirmation testing. Processes will be developed to support the manufacture of the first system, which was to have been sited and operated in Phase 4 but will now be sited and operated commercially by GE. This change has resulted from DOE's request to GE for deletion of Phase 4 in favor of a restructured Phase 3 (as Phase 3R) to include full speed, no load (FSNL) testing of the 7H gas turbine. Technology enhancements that are not required for the first machine design but will be critical for future ATS advances in performance, reliability, and costs will be initiated. Long-term tests of materials to confirm design life predictions will continue. A schematic of the GE H machine is shown. This report summarizes work accomplished in 2Q99.

  10. Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed.

    Science.gov (United States)

    Titova, Nataliya; Martinez-Martin, Pablo; Katunina, Elena; Chaudhuri, K Ray

    2017-12-01

    Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The "advanced" stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of "advanced Parkinson's disease" (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of "advanced" PD and also propose the term "complex phase" Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.

  11. Prototype system for phase advance measurements of LHC small beam oscillations

    CERN Document Server

    Olexa, J; Brezovic, Z; Gasior, M

    2013-01-01

    Magnet lattice parameters of the Large Hadron Collider (LHC) are measured by exciting beam transverse oscillations that allow measuring their phase advance using the beam position measurement (BPM) system. However, the BPM system requires millimetre oscillation amplitudes, with which nominal high intensity beams would cause large particle loss, dangerous for the LHC superconducting magnets. Therefore, such measurements cannot be done often, as they require special low intensity beams with important set-up time. After its first long shut-down the LHC will be equipped with new collimators with embedded BPMs, for which a new front-end electronics has been developed. Its main processing channels based on compensated diode detectors are designed for beam orbit measurement with sub-micrometre resolution. It is planned to extend this system by adding dedicated channels optimised for phase advance measurement, allowing continuous LHC optics measurement with much smaller beam excitation. This subsystem will be based o...

  12. Advanced Simulation Capability for Environmental Management - Current Status and Phase II Demonstration Results - 13161

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, Roger R.; Flach, Greg [Savannah River National Laboratory, Savannah River Site, Bldg 773-43A, Aiken, SC 29808 (United States); Freshley, Mark D.; Freedman, Vicky; Gorton, Ian [Pacific Northwest National Laboratory, MSIN K9-33, P.O. Box 999, Richland, WA 99352 (United States); Dixon, Paul; Moulton, J. David [Los Alamos National Laboratory, MS B284, P.O. Box 1663, Los Alamos, NM 87544 (United States); Hubbard, Susan S.; Faybishenko, Boris; Steefel, Carl I.; Finsterle, Stefan [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 50B-4230, Berkeley, CA 94720 (United States); Marble, Justin [Department of Energy, 19901 Germantown Road, Germantown, MD 20874-1290 (United States)

    2013-07-01

    The U.S. Department of Energy (US DOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Tool-sets and High-Performance Computing (HPC) Multi-process Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial tool-sets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  13. Advanced Simulation Capability for Environmental Management - Current Status and Phase II Demonstration Results - 13161

    International Nuclear Information System (INIS)

    Seitz, Roger R.; Flach, Greg; Freshley, Mark D.; Freedman, Vicky; Gorton, Ian; Dixon, Paul; Moulton, J. David; Hubbard, Susan S.; Faybishenko, Boris; Steefel, Carl I.; Finsterle, Stefan; Marble, Justin

    2013-01-01

    The U.S. Department of Energy (US DOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Tool-sets and High-Performance Computing (HPC) Multi-process Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial tool-sets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  14. Phase advance and β function measurements using model-independent analysis

    OpenAIRE

    Chun-xi Wang; Vadim Sajaev; Chih-Yuan Yao

    2003-01-01

    Phase advance and β function are basic lattice functions characterizing the linear properties of an accelerator lattice. Accurate and efficient measurements of these quantities are important for commissioning and operating a machine. For rings with little coupling, we report a new method to measure these lattice functions based on the model-independent analysis technique, which uses beam histories of excited betatron oscillations measured simultaneously at a large number of beam position moni...

  15. Advanced conceptual design report. Phase II. Liquid effluent treatment and disposal Project W-252

    International Nuclear Information System (INIS)

    1995-01-01

    This Advanced Conceptual Design Report (ACDR) provides a documented review and analysis of the Conceptual Design Report (CDR), WHC-SD-W252-CDR-001, June 30, 1993. The ACDR provides further design evaluation of the major design approaches and uncertainties identified in the original CDR. The ACDR will provide a firmer basis for the both the design approach and the associated planning for the performance of the Definitive Design phase of the project

  16. Advanced 3D Human Simulation Components with Thermal/Haptic Feedback and Tissue Deformation, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In integrating the following three significant components for its research/research and development (R/R&D) effort, the power of this candidate Phase II project...

  17. Advanced 3D Human Simulation Components with Thermal/Haptic Feedback and Tissue Deformation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — In integrating the following three significant components for its research/research and development (R/R&D) effort, the power of this candidate Phase I project...

  18. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

    2012-12-15

    Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

  19. Hepatocellular carcinoma: clinical significance of signal heterogeneity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, Nobuhiro; Nishie, Akihiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Moirta, Koichiro; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Fukuoka (Japan); Kubo, Yuichiro; Aishima, Shinichi [Kyushu University, Department of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka (Japan); Takayama, Yukihisa [Kyushu University, Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences, Fukuoka (Japan); Shirabe, Ken [Kyushu University, Department of Surgery and Science, Graduate School of Medical Sciences, Fukuoka (Japan)

    2015-01-15

    To clarify the relationship between the biological behaviour of hepatocellular carcinomas (HCCs) and their signal intensity in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging with a special focus on the signal heterogeneity. A total of 68 patients with 70 pathologically proven HCCs were enrolled. On the basis of the signal intensity in the hepatobiliary phase, the lesions were classified into three groups: group 1, homogeneous hypointensity (n = 44); group 2, heterogeneous hyperintensity (n = 20); and group 3, homogeneous hyperintensity (n = 6). The clinicopathological findings were compared among the three groups. The tumour size and the serum level of protein induced by vitamin K absence or antagonist-II (PIVKA-II) were significantly higher in group 2 compared to group 1 (p = 0.0155, p = 0.0215, respectively) and compared to group 3 (p = 0.0330, p = 0.0220, respectively). The organic anion transporting polypeptide 8 (OATP8) expression in group 2 and group 3 was significantly higher than in group 1 (p < 0.0001, p < 0.0001, respectively). Group 2 showed a significantly lower disease-free survival rate compared to group 1 (p = 0.0125), and group 2 was an independent prognostic factor for disease-free survival (p = 0.0308). HCCs in the hepatobiliary phase that are heterogeneously hyperintense on gadoxetic acid-enhanced MR imaging have more malignant potential than other types of HCCs. (orig.)

  20. Clinical Significance of Tumor Marker Detection in Patients 
with Advanced Squamous Cell Carcimoma of the Lung

    Directory of Open Access Journals (Sweden)

    Ping LIANG

    2016-10-01

    Full Text Available Background and objective Due to it's concealment and no obvious symptoms, lung squamous carcimoma often has advanced disease when diagnosed. The aims of this study were to describe the characteristics of the disease, to evaluate the clinical importance of detection of multiple tumor markers in patients with squamous cell carcinoma of the lung. Methods The characteristics of all patients with advanced squamous cell lung cancer treated in Beijing Cancer Hospital of Chinese Academy of Medical Sciences during Jan. 2011 to Dec. 2015 were identified by cases reviewing and data extracting. The characteristics, detection levels and sensitivity of multiple tumor makers among patients were described. Results The 260 patients were treated with mean age of (59.4±9.2 years, 85.8% (n=223 of them were male, 14.2% (n=37 of them were female. 78.1% (n=203 of all were smokers and 3.1% (n=8 of patients had family history of tumor. The positive rate of cytokerantin 19 fragment (CYFRA21-1 was 71.2%, which was the highest among five tumor markers. The five tumor markers median level had no statistical significance between different tumor (T stages and node (N stages (all P>0.05, only the positive rate of SCC had statistical significance between different T stages (P=0.035. The combination measurement of CYFRA21-1+carcinogen-embryonic antigen (CEA, CYFRA21-1+CEA+cancer antigen (CA125, CA125+CYFRA21-1+CEA+neuron specific enolase (NSE, and CA125+CYFRA21-1+NSE+CEA+squamous cell carcinoma antigen (SCC were better and had higher clinical values, the positive rates were 82.7%, 84.6%, 85.0% and 86.2%, respectively. Conclusion The positive rate of CYFRA21-1 was the highest and the sensitivity of single test of five tumor markers was low, the combination of multiple tumor markers increased the sensitivity of diagnosis of SQCLC, the combination of CA125, CYFRA21-1 and CEA was the best choice.

  1. Prognostic significance of the number of postoperative intraperitoneal chemotherapy cycles for patients with advanced epithelial ovarian cancer.

    Science.gov (United States)

    Suidan, Rudy S; Zhou, Qin; Iasonos, Alexia; O'Cearbhaill, Roisin E; Chi, Dennis S; Long Roche, Kara C; Tanner, Edward J; Denesopolis, John; Barakat, Richard R; Zivanovic, Oliver

    2015-05-01

    Phase 3 trials have demonstrated a survival advantage for patients with optimally debulked epithelial ovarian cancer who received intravenous (IV) and intraperitoneal (IP) chemotherapy compared with IV therapy alone. This was despite a significant proportion of patients in the IV/IP arms not completing all 6 planned cycles. Our objective was to evaluate the prognostic significance of the number of IV/IP cycles administered. Data were analyzed for all patients with stage III to IV epithelial ovarian cancer who underwent optimal primary cytoreduction followed by 1 or more cycles of IV/IP chemotherapy from January 2005 to July 2011 at our institution. A landmark analysis was performed to associate progression-free survival (PFS) and overall survival (OS) with the number of IV/IP cycles given. We identified 201 patients; 26 (13%) received 1 to 2 cycles of IV/IP chemotherapy, 41 (20%) received 3 to 4 cycles, and 134 (67%) received 5 to 6 cycles. The 5-year PFS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 18%, 29%, and 17%, respectively. The 5-year OS for patients who received 1 to 2, 3 to 4, and 5 to 6 cycles was 44%, 54%, and 57%, respectively. There was no significant difference in PFS (P = 0.31) or OS (P = 0.14) between the 3 groups. The most common reason for discontinuing IV/IP therapy was treatment-related toxicity (77%). Postoperative complications were the most common reason for not initiating IV/IP therapy (42%) in patients who subsequently transitioned to it. We did not detect a significant survival difference between patients who received 1 to 2, 3 to 4, or 5 to 6 IV/IP chemotherapy cycles. Women may still derive a survival benefit if they receive fewer than 6 IV/IP cycles.

  2. Advanced Dispersed Fringe Sensing Algorithm for Coarse Phasing Segmented Mirror Telescopes

    Science.gov (United States)

    Spechler, Joshua A.; Hoppe, Daniel J.; Sigrist, Norbert; Shi, Fang; Seo, Byoung-Joon; Bikkannavar, Siddarayappa A.

    2013-01-01

    Segment mirror phasing, a critical step of segment mirror alignment, requires the ability to sense and correct the relative pistons between segments from up to a few hundred microns to a fraction of wavelength in order to bring the mirror system to its full diffraction capability. When sampling the aperture of a telescope, using auto-collimating flats (ACFs) is more economical. The performance of a telescope with a segmented primary mirror strongly depends on how well those primary mirror segments can be phased. One such process to phase primary mirror segments in the axial piston direction is dispersed fringe sensing (DFS). DFS technology can be used to co-phase the ACFs. DFS is essentially a signal fitting and processing operation. It is an elegant method of coarse phasing segmented mirrors. DFS performance accuracy is dependent upon careful calibration of the system as well as other factors such as internal optical alignment, system wavefront errors, and detector quality. Novel improvements to the algorithm have led to substantial enhancements in DFS performance. The Advanced Dispersed Fringe Sensing (ADFS) Algorithm is designed to reduce the sensitivity to calibration errors by determining the optimal fringe extraction line. Applying an angular extraction line dithering procedure and combining this dithering process with an error function while minimizing the phase term of the fitted signal, defines in essence the ADFS algorithm.

  3. σ and η Phase formation in advanced polycrystalline Ni-base superalloys

    Energy Technology Data Exchange (ETDEWEB)

    Antonov, Stoichko, E-mail: santonov@hawk.iit.edu [Illinois Institute of Technology, 10 W. 32nd Street, Chicago, IL 60616 (United States); Huo, Jiajie; Feng, Qiang [State Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083 (China); Isheim, Dieter; Seidman, David N. [Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208 (United States); Northwestern University Center for Atom Probe Tomography (NUCAPT), 2220 Campus Drive, Evanston, IL 60208 (United States); Helmink, Randolph C.; Sun, Eugene [Rolls-Royce Corporation, 450 S. Meridian Street, Indianapolis, IN 46225 (United States); Tin, Sammy [Illinois Institute of Technology, 10 W. 32nd Street, Chicago, IL 60616 (United States)

    2017-02-27

    In polycrystalline Ni-base superalloys, grain boundary precipitation of secondary phases can be significant due to the effects they pose on the mechanical properties. As new alloying concepts for polycrystalline Ni-base superalloys are being developed to extend their temperature capability, the effect of increasing levels of Nb alloying additions on long term phase stability and the formation of topologically close packed (TCP) phases needs to be studied. Elevated levels of Nb can result in increased matrix supersaturation and promote the precipitation of secondary phases. Long term thermal exposures on two experimental powder processed Ni-base superalloys containing various levels of Nb were completed to assess the stability and precipitation of TCP phases. It was found that additions of Nb promoted the precipitation of η-Ni{sub 6}AlNb along the grain boundaries in powder processed, polycrystalline Ni-base superalloys, while reduced Nb levels favored the precipitation of blocky Cr and Mo – rich σ phase precipitates along the grain boundary. Evaluation of the thermodynamic stability of these two phases in both alloys using Thermo-calc showed that while σ phase predictions are fairly accurate, predictions of the η phase are limited.

  4. Evaluation of advanced two-phase flow instrumentation in SCTF Core-1

    International Nuclear Information System (INIS)

    Iwamura, Takamichi; Sobajima, Makoto; Osakabe, Masahiro; Ohnuki, Akira; Abe, Yutaka; Sudo, Yukio; Adachi, Hiromichi

    1984-03-01

    In the Slab Core Test Facility (SCTF) Core-I, advanced two-phase flow instruments have been provided by the USNRC to measure the thermohydraulic behavior in the primary system including pressure vessel during the end of blowdown, refill and reflood phases of a postulated loss-of-coolant accident in a pressurized water reactor. The advanced instruments are turbine meters, drag disks, γ-densitometers, spool pieces, liquid level detectors (LLD), fluid distribution grids (FDG), impedance probes (flag, prong and string probes), film probes, and video optical probes. This report presents evaluated results of the data from these instruments. Some instruments are quantitatively evaluated by comparing with the data from the conventional instruments or the other advanced instruments. Main conclusions are as follows: (1) The spool pieces and the γ-densitometers work well and provide satisfactory results; (2) Some of the turbine meters, the impedance probes and the film probes give partially reasonable results, but still more improvements are required; (3) Most of the LLDs, the FDGs, the impedance probes, and the film probes do not work well due to a hard cable corrosion, and (4) The video optical probes give clear image of the flow pattern. (author)

  5. Regorafenib for the Treatment of Advanced Gastric Cancer (INTEGRATE): A Multinational Placebo-Controlled Phase II Trial.

    Science.gov (United States)

    Pavlakis, Nick; Sjoquist, Katrin M; Martin, Andrew J; Tsobanis, Eric; Yip, Sonia; Kang, Yoon-Koo; Bang, Yung-Jue; Alcindor, Thierry; O'Callaghan, Christopher J; Burnell, Margot J; Tebbutt, Niall C; Rha, Sun Young; Lee, Jeeyun; Cho, Jae-Yong; Lipton, Lara R; Wong, Mark; Strickland, Andrew; Kim, Jin Won; Zalcberg, John R; Simes, John; Goldstein, David

    2016-08-10

    We evaluated the activity of regorafenib, an oral multikinase inhibitor, in advanced gastric adenocarcinoma. We conducted an international (Australia and New Zealand, South Korea, and Canada) randomized phase II trial in which patients were randomly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease (one v two) and region. Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred. The primary end point was progression-free survival (PFS). Final analysis included data to December 31, 2014. A total of 152 patients were randomly assigned from November 7, 2012, to February 25, 2014, yielding 147 evaluable patients (regorafenib, n = 97; placebo, n = 50). Baseline characteristics were balanced. Median PFS significantly differed between groups (regorafenib, 2.6 months; 95% CI, 1.8 to 3.1 and placebo, 0.9 months; 95% CI, 0.9 to 0.9; hazard ratio [HR], 0.40; 95% CI, 0.28 to 0.59; P regorafenib was seen (median, 5.8 months; 95% CI, 4.4 to 6.8 v 4.5 months; 95% CI, 3.4 to 5.2; HR, 0.74; P = .147). Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression. Regorafenib toxicity was similar to that previously reported. In this phase II trial, regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma. Regional differences were found, but regorafenib was effective in both regional groups. A phase III trial is planned. © 2016 by American Society of Clinical Oncology.

  6. Advanced Envelope Research for Factory Built Housing, Phase 3 -- Whole-House Prototyping

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E.; Mullens, M.; Rath, P.

    2014-04-01

    The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective envelope designs that can be effectively integrated into the plant production process while meeting the thermal requirements of the 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing new envelope technologies. This work is part of a multi-phase effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three methods for building high performance walls. Phase 2 focused on developing viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped narrow the research focus to perfecting a stud wall design with exterior continuous insulation (CI). Phase 3, completed in two stages, continued the design development effort, exploring and evaluating a range or methods for applying CI to factory built homes. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing. During this phase, a home was built with CI, evaluated, and placed in service. The experience of building a mock up wall section with CI and then constructing on line a prototype home resolved important concerns about how to integrate the material into the production process. First steps were taken toward finding least expensive approaches for incorporating CI in standard factory building practices and a preliminary assessment suggested that even at this early stage the technology is attractive when viewed from a life cycle cost perspective.

  7. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours.

    Science.gov (United States)

    Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

    2015-11-17

    This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours.

  8. Phase loop bandwidth measurements on the advanced photon source 352 MHz rf systems

    International Nuclear Information System (INIS)

    Horan, D.; Nassiri, A.; Schwartz, C.

    1997-01-01

    Phase loop bandwidth tests were performed on the Advanced Photon Source storage ring 352-MHz rf systems. These measurements were made using the HP3563A Control Systems Analyzer, with the rf systems running at 30 kilowatts into each of the storage ring cavities, without stored beam. An electronic phase shifter was used to inject approximately 14 degrees of stimulated phase shift into the low-level rf system, which produced measureable response voltage in the feedback loops without upsetting normal rf system operation. With the PID (proportional-integral-differential) amplifier settings at the values used during accelerator operation, the measurement data revealed that the 3-dB response for the cavity sum and klystron power-phase loops is approximately 7 kHz and 45 kHz, respectively, with the cavities the primary bandwidth-limiting factor in the cavity-sum loop. Data were taken at various PID settings until the loops became unstable. Crosstalk between the two phase loops was measured

  9. Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

    Science.gov (United States)

    Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

    2013-01-01

    Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

  10. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.

    Science.gov (United States)

    Wells, Samuel A; Robinson, Bruce G; Gagel, Robert F; Dralle, Henning; Fagin, James A; Santoro, Massimo; Baudin, Eric; Elisei, Rossella; Jarzab, Barbara; Vasselli, James R; Read, Jessica; Langmuir, Peter; Ryan, Anderson J; Schlumberger, Martin J

    2012-01-10

    There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments. Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%). Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).

  11. Synchronisation of the LHC Betatron Coupling and Phase Advance Measurement System

    CERN Document Server

    Gasior, M

    2014-01-01

    The new LHC Diode ORbit and OScillation (DOROS) system will provide beam position readings with submicrometre resolution and at the same time will be able to perform measurements of local betatron coupling and beam phase advance with micrometre beam excitation. The oscillation sub-system employs gain-controlled RF amplifiers, shared with the orbit system, and followed by dedicated diode detectors to demodulate the beam oscillation signals into the kHz frequency range, subsequently digitized by multi-channel 24-bit ADCs. The digital signals are processed in each front-end with an FPGA and the results of reduced throughput are sent using an Ethernet protocol to a common concentrator, together with the orbit data. The phase advance calculation between multiple Beam Position Monitors (BPMs) requires that all DOROS front-ends have a common phase reference. This paper presents methods used to generate such a reference and to maintain a stable synchronous sampling on all system front-ends. The performance of the DOR...

  12. Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas

    International Nuclear Information System (INIS)

    Hashimoto, Yosuke; Skacel, Marek; Lavery, Ian C; Mukherjee, Abir L; Casey, Graham; Adams, Josephine C

    2006-01-01

    Fascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index. Conventional tissue sections of 107 colorectal adenomas and 35 adenocarcinomas were analyzed by immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67 proliferation index were also investigated by use of a tissue microarray containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas linked to a CCF, IRB-approved database with a mean of 38 months of clinical follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox regression methods. Fascin was not expressed by the normal colonic epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas showed fascin expression in greater than 10% of the tumor cells. In the clinically-annotated tumors, fascin immunoreactivity was more common in tumors located in the proximal colon (p = 0.009), but was not associated with age, gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with strong fascin immunoreactivity had a worse prognosis than patients with low or absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely correlated at the cellular level; this trend was less apparent in adenocarcinomas. Fascin is upregulated in a proportion of adenomas, where its expression is often focal. Strong and diffuse expression was seen in a subset of advanced colorectal adenocarcinomas that correlated with shorter survival in stage III and IV patients. Fascin may have

  13. Does advanced lung inflammation index (ALI) have prognostic significance in metastatic non-small cell lung cancer?

    Science.gov (United States)

    Ozyurek, Berna Akinci; Ozdemirel, Tugce Sahin; Ozden, Sertac Buyukyaylaci; Erdoğan, Yurdanur; Ozmen, Ozlem; Kaplan, Bekir; Kaplan, Tugba

    2018-01-22

    Lung cancer is the most commonly diagnosed and death-related cancer type and is more frequent in males. Non-small-cell lung cancer (NSCLC) accounts for about 85% of all case. In this study, it was aimed to research the relationship between advanced lung inflammation index (ALI) and the primary mass maximum standardized uptake value (SUVmax) and C-reactive protein (CRP) at initial diagnosis and the prognostic value of ALI in determining the survival in metastatic NSCLC. A total of 112 patients diagnosed as stage 4 non-small-lung cancer in our hospital between January 2006 and December 2013 were included in this study. ALI was calculated as body mass index (BMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR). The patients were divided into two groups as ALI ALI ≥ 18 (low inflammation). The log-rank test and Cox proportional hazard model were used to identify predictors of mortality. Evaluation was made of 94 male and 18 female patients with a mean age of 59.7 ± 9.9 years. A statistically significant negative relationship was determined between ALI and CRP values (P ALI and SUVmax values (P = .436). The median survival time in patients with ALI ALI ≥ 18, it was 16 months (P = .095). ALI is an easily calculated indicator of inflammation in lung cancer patients. Values <18 can be considered to predict a poor prognosis. © 2018 John Wiley & Sons Ltd.

  14. Aluminum-centered tetrahedron-octahedron transition in advancing Al-Sb-Te phase change properties.

    Science.gov (United States)

    Xia, Mengjiao; Ding, Keyuan; Rao, Feng; Li, Xianbin; Wu, Liangcai; Song, Zhitang

    2015-02-24

    Group IIIA elements, Al, Ga, or In, etc., doped Sb-Te materials have proven good phase change properties, especially the superior data retention ability over popular Ge2Sb2Te5, while their phase transition mechanisms are rarely investigated. In this paper, aiming at the phase transition of Al-Sb-Te materials, we reveal a dominant rule of local structure changes around the Al atoms based on ab initio simulations and nuclear magnetic resonance evidences. By comparing the local chemical environments around Al atoms in respective amorphous and crystalline Al-Sb-Te phases, we believe that Al-centered motifs undergo reversible tetrahedron-octahedron reconfigurations in phase transition process. Such Al-centered local structure rearrangements significantly enhance thermal stability of amorphous phase compared to that of undoped Sb-Te materials, and facilitate a low-energy amorphization due to the weak links among Al-centered and Sb-centered octahedrons. Our studies may provide a useful reference to further understand the underlying physics and optimize performances of all IIIA metal doped Sb-Te phase change materials, prompting the development of NOR/NAND Flash-like phase change memory technology.

  15. Reflooding phase after loss of coolant of an advanced pressurized water reactor with high conversion ratio

    International Nuclear Information System (INIS)

    Schumann, S.

    1984-01-01

    The emergency core cooling behaviour of an advanced pressurized water reactor (APWR) during the reflooding phase of the LOCA with double-ended break is analysed and compared to a common pressurized water reactor (PWR). The code FLUT-BS, its models and correlations are explained in detail and have been verified by numerous PWR-reflood experiments with large parameter range. The influence of core-design on ECC-behaviour as well as the influences of initial and boundary values are examined. The results show the essential differences of ECC-behaviour between PWR and APWR. (orig.) [de

  16. Computed phase equilibria for burnable neutron absorbing materials for advanced pressurized heavy water reactors

    Energy Technology Data Exchange (ETDEWEB)

    Corcoran, E.C. [Department of Chemistry and Chemical Engineering, Royal Military College of Canada, P.O. Box 17000, St. Forces, Kingston, Ont., K7K 7B4 (Canada)], E-mail: emily.corcoran@rmc.ca; Lewis, B.J.; Thompson, W.T. [Department of Chemistry and Chemical Engineering, Royal Military College of Canada, P.O. Box 17000, St. Forces, Kingston, Ont., K7K 7B4 (Canada); Hood, J. [Atomic Energy of Canada Ltd., Sheridan Park, 2251 Speakman Drive, Mississauga, Ont., L5K 1B2 (Canada); Akbari, F.; He, Z. [Atomic Energy of Canada Ltd., Chalk River Laboratories, Chalk River, Ont., K0J 1J0 (Canada); Reid, P. [Atomic Energy of Canada Ltd., Sheridan Park, 2251 Speakman Drive, Mississauga, Ont., L5K 1B2 (Canada)

    2009-03-31

    Burnable neutron absorbing materials are expected to be an integral part of the new fuel design for the Advanced CANDU [CANDU is as a registered trademark of Atomic Energy of Canada Limited.] Reactor. The neutron absorbing material is composed of gadolinia and dysprosia dissolved in an inert cubic-fluorite yttria-stabilized zirconia matrix. A thermodynamic model based on Gibbs energy minimization has been created to provide estimated phase equilibria as a function of composition and temperature. This work includes some supporting experimental studies involving X-ray diffraction.

  17. Subsonic Ultra Green Aircraft Research Phase II: N+4 Advanced Concept Development

    Science.gov (United States)

    Bradley, Marty K.; Droney, Christopher K.

    2012-01-01

    This final report documents the work of the Boeing Subsonic Ultra Green Aircraft Research (SUGAR) team on Task 1 of the Phase II effort. The team consisted of Boeing Research and Technology, Boeing Commercial Airplanes, General Electric, and Georgia Tech. Using a quantitative workshop process, the following technologies, appropriate to aircraft operational in the N+4 2040 timeframe, were identified: Liquefied Natural Gas (LNG), Hydrogen, fuel cell hybrids, battery electric hybrids, Low Energy Nuclear (LENR), boundary layer ingestion propulsion (BLI), unducted fans and advanced propellers, and combinations. Technology development plans were developed.

  18. Treatment of reduced sulphur compounds and SO2 by Gas Phase Advanced Oxidation

    DEFF Research Database (Denmark)

    Meusinger, Carl; Bluhme, Anders Brostrøm; Ingemar, Jonas L.

    2017-01-01

    Reduced sulphur compounds (RSCs) emitted from pig farms are a major problem for agriculture, due to their health and environmental impacts and foul odour. This study investigates the removal of RSCs, including H2S, and their oxidation product SO2 using Gas Phase Advanced Oxidation (GPAO). GPAO...... is a novel air cleaning technique which utilises accelerated atmospheric chemistry to oxidise pollutants before removing their oxidation products as particles. Removal efficiencies of 24.5% and 3.9% were found for 461 ppb of H2S and 714 ppb of SO2 in a laboratory system (volumetric flow Q = 75 m3/h......). A numerical model of the reactor system was developed to explore the basic features of the system; its output was in fair agreement with the experiment. The model verified the role of OH radicals in initiating the oxidation chemistry. All sulphur removed from the gas phase was detected as particulate matter...

  19. Nondestructive Evaluation of Advanced Materials with X-ray Phase Mapping

    Science.gov (United States)

    Hu, Zhengwei

    2005-01-01

    X-ray radiation has been widely used for imaging applications since Rontgen first discovered X-rays over a century ago. Its large penetration depth makes it ideal for the nondestructive visualization of the internal structure and/or defects of materials unobtainable otherwise. Currently used nondestructive evaluation (NDE) tools, X-ray radiography and tomography, are absorption-based, and work well in heavy-element materials where density or composition variations due to internal structure or defects are high enough to produce appreciable absorption contrast. However, in many cases where materials are light-weight and/or composites that have similar mass absorption coefficients, the conventional absorption-based X-ray methods for NDE become less useful. Indeed, the light-weight and ultra-high-strength requirements for the most advanced materials used or developed for current flight mission and future space exploration pose a great challenge to the standard NDE tools in that the absorption contrast arising from the internal structure of these materials is often too weak to be resolved. In this presentation, a solution to the problem, the use of phase information of X-rays for phase contrast X-ray imaging, will be discussed, along with a comparison between the absorption-based and phase-contrast imaging methods. Latest results on phase contrast X-ray imaging of lightweight Space Shuttle foam in 2D and 3D will be presented, demonstrating new opportunities to solve the challenging issues encountered in advanced materials development and processing.

  20. STUDY OF CORRELATION AND SIGNIFICANCE OF BIOCHEMICAL PARAMETERS IN THE ASSESSMENT OF ACTIVE PHASE OF THYROID EYE DISEASE

    Directory of Open Access Journals (Sweden)

    Ashok Kumar P

    2016-08-01

    Full Text Available AIM Role of Interleukin-6 and HS-CRP Levels in the assessment of active thyroid eye disease. MATERIALS & METHODS A prospective observational study of 30 patients from the age group of 20-60 years with thyroid eye disease done at Regional Institute of Ophthalmology. All patients were subjected to detailed history, ocular examination, systemic examination, biochemical analysis and Imaging. Patients are categorised as mild, moderate and severe active disease based on clinical activity score. For the period of two years, patients are followed at regular periodic intervals according to the severity of disease and results were analysed. RESULTS Out of 30 patients studied, majority of the patients were females (60%, and 70% of the patients had bilateral disease. Among 30 patients, 83.33% in hyperthyroid state, 3.33% in Hypothyroid state, 13.33% in Euthyroid state (Table 3. Smoking being important risk factor in 30% among males. 50% of patients presented with mild disease, 30% with moderate disease, 0% with severe disease. IL-6, HS-CRP levels are increased only in patients with severe active disease (Table 6. Remission attained in all patients when treated earlier with steroids. CONCLUSION Identifying disease activity early and aggressive treatment with systemic steroids in active phase of moderate and severe disease has reduced the morbidity associated with disease. Correlation of IL-6, HS-CRP, TFT levels are significantly increased only in patients with active phase of severe thyroid eye disease but not significantly elevated in active phase of moderate disease. Another pitfall is IL-6 is an expensive ELISA based diagnosis. Thus, IL-6 & HS-CRP cannot be routinely used to screen patients with Thyroid eye disease.

  1. Gender differences on the job satisfaction in the phase of implementing advanced manufacturing technology in the Chinese manufacturing firms.

    Science.gov (United States)

    Yu, Na; Shen, Li Ming; Lewark, Siegfried

    2012-01-01

    This research gave an effort to study on gender differences in the job satisfaction for technological innovation at Chinese manufacturing firm. The exploratory study was conducted in four Chinese furniture manufacturing firms, which are all in the phases of introducing advanced manufacturing system. The results of statistical analysis show that general satisfaction of female employees to their jobs is significantly higher than male employees. In addition, supervisory satisfaction of female employees is significantly higher than male employees. The findings of the study reveal that activities are suggested to be carried out to increase the job satisfaction of male employees, especially improve communication and relationship between the managerial and the non-managerial levels in the innovation process. In addition, the higher job satisfaction of female employees could be considered a positive factor for the successful implementation of AMT in the technological innovation, although male employees are still dominated work force in the case study firms.

  2. Advanced Envelope Research for Factory Built Housing, Phase 3. Whole-House Prototyping

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E. [Advanced Residential Integrated Energy Solutions (ARIES), New York, NY (United States); Mullens, M. [Advanced Residential Integrated Energy Solutions (ARIES), New York, NY (United States); Rath, P. [Advanced Residential Integrated Energy Solutions (ARIES), New York, NY (United States)

    2014-04-01

    The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective envelope designs that can be effectively integrated into the plant production process while meeting the thermal requirements of the 2012 IECC standards. This work is part of a multiphase effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three methods for building high performance walls. Phase 2 focused on developing viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped narrow the research focus to perfecting a stud wall design with exterior continuous insulation (CI). This report describes Phase 3, which was completed in two stages and continued the design development effort, exploring and evaluating a range or methods for applying CI to factory built homes. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing. During this phase, a home was built with CI, evaluated, and placed in service. The experience of building a mock up wall section with CI and then constructing on line a prototype home resolved important concerns about how to integrate the material into the production process. First steps were taken toward finding least expensive approaches for incorporating CI in standard factory building practices and a preliminary assessment suggested that even at this early stage the technology is attractive when viewed from a life cycle cost perspective.

  3. Body composition, symptoms, and survival in advanced cancer patients referred to a phase I service.

    Science.gov (United States)

    Parsons, Henrique A; Baracos, Vickie E; Dhillon, Navjot; Hong, David S; Kurzrock, Razelle

    2012-01-01

    Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown. We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI); body composition was evaluated utilizing computerized tomography(CT) images. A body mass index (BMI)≥25 kg/m² was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria. Most patients were overweight (n = 65, 63%); 53 patients were sarcopenic (51%), including 79% of patients with a BMIbody composition: 215 (71-358) (BMIcancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index. Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI≥25 kg/m², independent of symptom burden. Body composition variables were predictive of clinically relevant survival differences, which is potentially important in developing Phase I studies.

  4. Advanced Envelope Research for Factory Built Housing, Phase 3 -- Design Development and Prototyping

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kessler, B. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mullens, M. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Rath, P. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-01-01

    The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective alternative envelope designs. In the near term, these technologies will play a central role in meeting stringent energy code requirements. For manufactured homes, the thermal requirements, last updated by statute in 1994, will move up to the more rigorous IECC 2012 levels in 2013, the requirements of which are consistent with site built and modular housing. This places added urgency on identifying envelope technologies that the industry can implement in the short timeframe. The primary goal of this research is to develop wall designs that meet the thermal requirements based on 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing the new envelope technologies. This work is part of a four-phase, multi-year effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three selected methods for building high performance wall systems. Phase 2 focused on the development of viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped critique and select the most viable solution to move further in the research -- stud walls with continuous exterior insulation. Phase 3, the subject of the current report, focused on the design development of the selected wall concept and explored variations on the use of exterior foam insulation. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing.

  5. Advanced Envelope Research for Factory Built Housing, Phase 3. Design Development and Prototyping

    Energy Technology Data Exchange (ETDEWEB)

    Levy, E. [ARIES Collaborative, New York, NY (United States); Kessler, B. [ARIES Collaborative, New York, NY (United States); Mullens, M. [ARIES Collaborative, New York, NY (United States); Rath, P. [ARIES Collaborative, New York, NY (United States)

    2014-01-01

    The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective alternative envelope designs. In the near term, these technologies will play a central role in meeting stringent energy code requirements. For manufactured homes, the thermal requirements, last updated by statute in 1994, will move up to the more rigorous IECC 2012 levels in 2013, the requirements of which are consistent with site built and modular housing. This places added urgency on identifying envelope technologies that the industry can implement in the short timeframe. The primary goal of this research is to develop wall designs that meet the thermal requirements based on 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing the new envelope technologies. This work is part of a four-phase, multi-year effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three selected methods for building high performance wall systems. Phase 2 focused on the development of viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped critique and select the most viable solution to move further in the research -- stud walls with continuous exterior insulation. Phase 3, the subject of the current report, focused on the design development of the selected wall concept and explored variations on the use of exterior foam insulation. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing.

  6. Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Movsas, Benjamin; Hanlon, Alexandra L.; Lanciano, Rachelle; Scher, Richard M.; Weiner, Louis M.; Sigurdson, Elin R.; Hoffman, John P.; Eisenberg, Burton L.; Cooper, Harry S.; Provins, Susan; Coia, Lawrence R.

    1998-01-01

    in 7. Four patients did not undergo a curative resection; three initially presented with metastases and one developed metastasis during the pre-operative regimen. Post-operative complications included pelvic or perineal abscess in two (on dose Levels I and II), and delayed wound healing in two (one of whom, on dose Level III, developed perineal wound dehiscence requiring surgical reconstruction). Of the 23 patients who had a curative resection, four manifested pathologic complete responses (17.4%). Thirteen of 23 patients (57%) had evidence of pathologic downstaging and only 1/23 patients (on dose Level I) had a positive resection margin. Of these 23 patients (with a minimum follow-up of 8 months), the patient with positive margins was the only one who developed a local failure (Fisher's Exact p = .04). The 3-year actuarial OS, DFS and LC rates are 82%, 72% and 96%, respectively. Twelve of 13 patients (92% at 3 years) ≥ 61 years vs. 5/10 patients (45% at 3 years) < 61 years remained disease-free (log-rank p = 0.017). Conclusion: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p = 0.04). Older age (≥61 years) was a significant predictor for improved DFS. This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting

  7. A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate

    DEFF Research Database (Denmark)

    Iversen, P; Christensen, M G; Friis, E

    1990-01-01

    In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor of the co......In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor...... of the combination therapy, whereas no statistically significant difference was found in subjective response to therapy, time to progression, and overall survival. Adverse effects were more commonly encountered in the pharmacologically treated patients. It is concluded that the combination of zoladex plus flutamide...... is not clinically superior to orchiectomy in the treatment of patients with advanced carcinoma of the prostate....

  8. Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

    Science.gov (United States)

    Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

    2010-09-01

    This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

  9. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma

    NARCIS (Netherlands)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J. A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with

  10. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    NARCIS (Netherlands)

    Ribas, A.; Kefford, R.; Marshall, Martin; Punt, C.J.A.; Haanen, J.B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K.L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G.A.; Dreno, B.; Nathan, P.D.; Mackiewicz, J.; Kirkwood, J.M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A.

    2013-01-01

    PURPOSE: In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients

  11. Increased levels of proteins of the acute inflammatory phase in the peritoneal fluid of women with advanced stages of endometriosis.

    Science.gov (United States)

    Polak, Grzegorz; Barczyński, Bartłomiej; Bednarek, Wiesława; Kwaśniewski, Wojciech; Wertell, Iwona; Derewianka-Polak, Magdalena; Makara-Studzińska, Marta; Kotarski, Jan

    2015-06-01

    Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.

  12. A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    Chi, K.-H.; Chang, Y.-C.; Guo, W.-Y.; Leung, M.-J.; Shiau, C.-Y.; Chen, S.-Y; Wang, L.-W.; Lai, Y.-L.; Hsu, M.-M.; Lian, S.-L.; Chang, C.-H.; Liu, T.-W.; Chin, Y.-H.; Yen, S.-H.; Perng, C.-H.; Chen, Kuang Y.

    2002-01-01

    Purpose: To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC. Methods and Materials: Between November 1994 and March 1999, 157 patients with Stage IV, M 0 (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35-40 fractions, 1.8-2.0 Gy/fraction/day, 5 days/week, to a total dose 70-72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m 2 cisplatin, 2,200 mg/m 2 5-fluorouracil, and 120 mg/m 2 leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis. Results: With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p value = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (≥ Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (≥ Grade 3). Conclusions: We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival

  13. Gas-phase advanced oxidation as an integrated air pollution control technique

    Directory of Open Access Journals (Sweden)

    Getachew A. Adnew

    2016-03-01

    Full Text Available Gas-phase advanced oxidation (GPAO is an emerging air cleaning technology based on the natural self-cleaning processes that occur in the Earth’s atmosphere. The technology uses ozone, UV-C lamps and water vapor to generate gas-phase hydroxyl radicals that initiate oxidation of a wide range of pollutants. In this study four types of GPAO systems are presented: a laboratory scale prototype, a shipping container prototype, a modular prototype, and commercial scale GPAO installations. The GPAO systems treat volatile organic compounds, reduced sulfur compounds, amines, ozone, nitrogen oxides, particles and odor. While the method covers a wide range of pollutants, effective treatment becomes difficult when temperature is outside the range of 0 to 80 °C, for anoxic gas streams and for pollution loads exceeding ca. 1000 ppm. Air residence time in the system and the rate of reaction of a given pollutant with hydroxyl radicals determine the removal efficiency of GPAO. For gas phase compounds and odors including VOCs (e.g. C6H6 and C3H8 and reduced sulfur compounds (e.g. H2S and CH3SH, removal efficiencies exceed 80%. The method is energy efficient relative to many established technologies and is applicable to pollutants emitted from diverse sources including food processing, foundries, water treatment, biofuel generation, and petrochemical industries.

  14. HATT: a phase IV, single-arm, open-label study of sorafenib in Taiwanese patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Shi-Ming; Lu, Sheng-Nan; Chen, Ping-Tsung; Jeng, Long-Bin; Chen, Shinn-Cherng; Hu, Chi-Tan; Yang, Sien-Sing; Le Berre, Marie-Aude; Liu, Xuan; Mitchell, David Y; Prins, Klaas; Grevel, Joachim; Peña, Carol A E; Meinhardt, Gerold

    2017-03-01

    Sorafenib significantly improves survival in patients with advanced hepatocellular carcinoma (HCC). This phase IV study assessed sorafenib efficacy/safety in Taiwanese patients with advanced HCC and Child-Pugh A status. All patients received 400 mg sorafenib BID. Safety, efficacy, sorafenib pharmacokinetics, and Child-Pugh progression were evaluated. A hand-foot skin reaction (HFSR) prevention substudy assessed HFSR incidence and grade/severity and time to HFSR in 29 and 34 patients randomized to corticosteroid and noncorticosteroid ointments, respectively, and in 88 nonrandomized patients. The 151 patients included 120 (80%) male patients and 81 (54%) with stage IV disease. Mean sorafenib dose was 626 mg/day, and median treatment duration was 4.2 months. Median overall survival (OS), progression-free survival, and time to progression (TTP) were 8.6, 2.7, and 3.8 months, respectively. Disease control and response rates (partial responses only) were 48 and 6.6%, respectively. Median TTP from Child-Pugh A to B/C was 88 days. Drug-related adverse events (AEs) occurred in 89.4% of patients; none were new or unexpected. The most frequent grade ≥3 drug-related, treatment-emergent AEs were HFSR (13.2%), diarrhea (11.9%), and hypertension (6.6%). Corticosteroid ointment tended to reduce the severity and incidence of all HFSR-associated parameters. Pharmacokinetic exposure was unaltered by Child-Pugh progression. The final pharmacokinetic model predicted 13.1 and 33.8% reductions in sorafenib exposure over 6 and 12 months, respectively. There was a trend of longer OS and TTP in Taiwanese patients with advanced HCC compared with patients with advanced HCC in the Asia-Pacific trial. Sorafenib exposure did not correlate with liver function. Reduced pharmacokinetic exposure over time was unrelated to reduced or interrupted dosing.

  15. Body composition, symptoms, and survival in advanced cancer patients referred to a phase I service.

    Directory of Open Access Journals (Sweden)

    Henrique A Parsons

    Full Text Available Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown.We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI; body composition was evaluated utilizing computerized tomography(CT images. A body mass index (BMI≥25 kg/m² was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria.Most patients were overweight (n = 65, 63%; 53 patients were sarcopenic (51%, including 79% of patients with a BMI<25 kg/m² and 34% of those with BMI≥25 kg/m². Sarcopenic patients were older and less frequently African-American. Symptom burden did not differ among patients classified according to BMI and presence of sarcopenia. Median (95% confidence interval survival (days varied according to body composition: 215 (71-358 (BMI<25 kg/m²; sarcopenic, 271 (99-443 (BMI<25 kg/m²; non-sarcopenic, 484 (286-681 (BMI≥25 kg/m²; sarcopenic; 501 d (309-693 (BMI≥25 kg/m²; non-sarcopenic. Higher muscle index and gastrointestinal cancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index.Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI≥25 kg/m², independent of symptom burden. Body composition variables were predictive of clinically relevant survival differences, which is potentially important in developing Phase I studies.

  16. Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

    Science.gov (United States)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J.A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    Purpose In phase I/II trials, the cytotoxic T lymphocyte–associated antigen-4–blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma. PMID:23295794

  17. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    Science.gov (United States)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A; Punt, Cornelis J A; Haanen, John B; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A; Dreno, Brigitte; Nathan, Paul D; Mackiewicz, Jacek; Kirkwood, John M; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-02-10

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.

  18. Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism and Efflux Transport.

    Science.gov (United States)

    Wang, Shuai; Xing, Huijie; Zhao, Mengjing; Lu, Danyi; Li, Zhijie; Dong, Dong; Wu, Baojian

    2016-01-01

    Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism. In this article, we review the studies investigating the phase II metabolism-transport interplay using cell models, perfused rat intestine, and intact rats. The potential confounding factors in exploring such interplay is also summarized. Moreover, the mechanism underlying the phase II metabolism-transport interplay is discussed. Various studies with engineered cells and rodents have demonstrated that there is an interaction (interplay) between phase II enzymes and efflux transporters. This type of interplay mainly refers to the dependence of phase II (conjugative) metabolism on the activities of efflux transporters. In general, inhibiting efflux transporters or decreasing their expression causes the reductions in metabolite excretion, apparent excretion clearance (CLapp) and total metabolism (fmet), as well as an increase in the intracellular level of metabolite (Ci). The deconjugation mediated by hydrolase (acting as a "bridge") is essential for the interplay to play out based on pharmacokinetic modeling/simulations, cell and animal studies. The hydrolases bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof (a bridging effect). Without the bridge, metabolite formation is independent on its downstream process excretion, thus impact of metabolite excretion on its formation is impossible

  19. Regolith Advanced Surface Systems Operations Robot (RASSOR) Phase 2 and Smart Autonomous Sand-Swimming Excavator

    Science.gov (United States)

    Sandy, Michael

    2015-01-01

    The Regolith Advanced Surface Systems Operations Robot (RASSOR) Phase 2 is an excavation robot for mining regolith on a planet like Mars. The robot is programmed using the Robotic Operating System (ROS) and it also uses a physical simulation program called Gazebo. This internship focused on various functions of the program in order to make it a more professional and efficient robot. During the internship another project called the Smart Autonomous Sand-Swimming Excavator was worked on. This is a robot that is designed to dig through sand and extract sample material. The intern worked on programming the Sand-Swimming robot, and designing the electrical system to power and control the robot.

  20. Application of advanced statistical methods in assessment of the late phase of a nuclear accident

    International Nuclear Information System (INIS)

    Hofman, R.

    2008-01-01

    The paper presents a new methodology for improving of estimates of radiological situation on terrain in the late phase of a nuclear accident. Methods of Bayesian filtering are applied to the problem. The estimates are based on combination of modeled and measured data provided by responsible authorities. Exploiting information on uncertainty of both the data sources, we are able to produce improved estimate of the true situation on terrain. We also attempt to account for model error, which is unknown and plays crucial role in accuracy of the estimates. The main contribution of this paper is application of an approach based on advanced statistical methods, which allows for estimating of model error covariance structure upon measurements. Model error is estimated on basis of measured-minus-observed residuals evaluated upon measured and modeled values. The methodology is demonstrated on a sample scenario with simulated measurements. (authors)

  1. Advanced conceptual design report solid waste retrieval facility, phase I, project W-113

    International Nuclear Information System (INIS)

    Smith, K.E.

    1994-01-01

    Project W-113 will provide the equipment and facilities necessary to retrieve suspect transuranic (TRU) waste from Trench 04 of the 218W-4C burial ground. As part of the retrieval process, waste drums will be assayed, overpacked, vented, head-gas sampled, and x-rayed prior to shipment to the Phase V storage facility in preparation for receipt at the Waste Receiving and Processing Facility (WRAP). Advanced Conceptual Design (ACD) studies focused on project items warranting further definition prior to Title I design and areas where the potential for cost savings existed. This ACD Report documents the studies performed during FY93 to optimize the equipment and facilities provided in relation to other SWOC facilities and to provide additional design information for Definitive Design

  2. Application of advanced statistical methods in assessment of the late phase of a nuclear accident

    International Nuclear Information System (INIS)

    Hofman, R.

    2009-01-01

    The paper presents a new methodology for improving of estimates of radiological situation on terrain in the late phase of a nuclear accident. Methods of Bayesian filtering are applied to the problem. The estimates are based on combination of modeled and measured data provided by responsible authorities. Exploiting information on uncertainty of both the data sources, we are able to produce improved estimate of the true situation on terrain. We also attempt to account for model error, which is unknown and plays crucial role in accuracy of the estimates. The main contribution of this paper is application of an approach based on advanced statistical methods, which allows for estimating of model error covariance structure upon measurements. Model error is estimated on basis of measured-minus-observed residuals evaluated upon measured and modeled values. The methodology is demonstrated on a sample scenario with simulated measurements. (authors)

  3. Diffusion, Thermal Properties and Chemical Compatibilities of Select MAX Phases with Materials For Advanced Nuclear Systems

    Energy Technology Data Exchange (ETDEWEB)

    Barsoum, Michel [Drexel Univ., Philadelphia, PA (United States); Bentzel, Grady [Drexel Univ., Philadelphia, PA (United States); Tallman, Darin J. [Drexel Univ., Philadelphia, PA (United States); Sindelar, Robert [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Garcia-Diaz, Brenda [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hoffman, Elizabeth [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-04-04

    The demands of Gen IV nuclear power plants for long service life under neutron irradiation at high temperature are severe. Advanced materials that would withstand high temperatures (up to 1000+ ºC) to high doses in a neutron field would be ideal for reactor internal structures and would add to the long service life and reliability of the reactors. The objective of this work is to investigate the chemical compatibility of select MAX with potential materials that are important for nuclear energy, as well as to measure the thermal transport properties as a function of neutron irradiation. The chemical counterparts chosen for this work are: pyrolytic carbon, SiC, U, Pd, FLiBe, Pb-Bi and Na, the latter 3 in the molten state. The thermal conductivities and heat capacities of non-irradiated MAX phases will be measured.

  4. Gas-phase advanced oxidation for effective, efficient in situ control of pollution

    DEFF Research Database (Denmark)

    Johnson, Matthew Stanley; Nilsson, Elna Johanna Kristina; Svensson, Erik Anders

    2014-01-01

    In this article, gas-phase advanced oxidation, a new method for pollution control building on the photo-oxidation and particle formation chemistry occurring in the atmosphere, is introduced and characterized. The process uses ozone and UV-C light to produce in situ radicals to oxidize pollution......, generating particles that are removed by a filter; ozone is removed using a MnO2 honeycomb catalyst. This combination of in situ processes removes a wide range of pollutants with a comparatively low specific energy input. Two proof-of-concept devices were built to test and optimize the process...... particulate mass. Secondary pollution including formaldehyde and ultrafine particles might be generated, depending on the composition of the primary pollution....

  5. Parkinsonian syndromes presenting with circadian rhythm sleep disorder- advanced sleep-phase type.

    Science.gov (United States)

    Shukla, Garima; Kaul, Bhavna; Gupta, Anupama; Goyal, Vinay; Behari, Madhuri

    2015-01-01

    Circadian rhythm sleep disorder-advanced sleep-phase type is a relatively uncommon disorder, mostly seen among the elderly population. Impaired circadian rhythms have been reported in neurodegenerative conditions; however, there are no reports of any circadian rhythm sleep disorder among patients with Parkinsonian syndromes. We report two patients who presented with this circadian rhythm disorder, and were then diagnosed with a Parkinsonian syndrome. The cases. A 65-year-old retired man presented with history of abrupt change in sleep schedules, sleeping around 6.30-7 p.m. and waking up around 3-4 a.m. for the last 2 months. On detailed examination, the patient was observed to have symmetrical bradykinesia and cogwheel rigidity of limbs. A diagnosis of multiple system atrophy was made, supported by MRI findings and evidence of autonomic dysfunction. Symptoms of change in sleep-wake cycles resolved over the next 1 year, while the patient was treated with dopaminergic therapy. A 47-year-old man, who was being evaluated for presurgical investigation for refractory temporal lobe epilepsy, presented with complaints suggestive of dysarthria, bradykinesia of limbs and frequent falls for 5 months. Simultaneously, he began to sleep around 7 p.m. and wake up at about 2-3 a.m. Examination revealed severe axial rigidity, restricted vertical gaze and bradykinesia of limbs. A diagnosis of progressive supranuclear palsy was made. This is the first report of Parkinson's plus syndromes presenting with a circadian rhythm sleep disorder-advanced sleep-phase type. More prospective assessment for circadian sleep disorders may introduce useful insights into similar associations. Copyright 2015, NMJI.

  6. Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

    2018-01-01

    The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Phase 2 Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer

    Science.gov (United States)

    Philip, Philip A.; Mahoney, Michelle R.; Holen, Kyle D.; Northfelt, Donald W.; Pitot, Henry C.; Picus, Joel; Flynn, Patrick J.; Erlichman, Charles

    2013-01-01

    BACKGROUND Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC). METHODS Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child’s Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point. RESULTS Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child’s A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea. CONCLUSIONS In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. PMID:21953248

  8. Autonomic nervous system dynamics for mood and emotional-state recognition significant advances in data acquisition, signal processing and classification

    CERN Document Server

    Valenza, Gaetano

    2014-01-01

    This monograph reports on advances in the measurement and study of autonomic nervous system (ANS) dynamics as a source of reliable and effective markers for mood state recognition and assessment of emotional responses. Its primary impact will be in affective computing and the application of emotion-recognition systems. Applicative studies of biosignals such as: electrocardiograms; electrodermal responses; respiration activity; gaze points; and pupil-size variation are covered in detail, and experimental results explain how to characterize the elicited affective levels and mood states pragmatically and accurately using the information thus extracted from the ANS. Nonlinear signal processing techniques play a crucial role in understanding the ANS physiology underlying superficially noticeable changes and provide important quantifiers of cardiovascular control dynamics. These have prognostic value in both healthy subjects and patients with mood disorders. Moreover, Autonomic Nervous System Dynamics for Mood and ...

  9. A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

    Science.gov (United States)

    Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

    2002-03-01

    To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being Phase II dose. The area under the concentration time curve increased in proportion to administered dose, and the clearance remained constant over the dose range studied. Correlation analysis demonstrated relationships between dose and area under the concentration with cycle 1 hematological parameters, including absolute neutrophil and leukocyte nadirs. Bizelesin administered every 4 weeks as an i.v. push is well tolerated with dose-limiting toxicity of neutropenia. The maximum-tolerated dose (and recommended Phase II dose) is 0.8 microg/m(2) administered once every 4 weeks.

  10. A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus).

    Science.gov (United States)

    Weiss, Glen J; Waypa, Jordan; Blaydorn, Lisa; Coats, Jessica; McGahey, Kayla; Sangal, Ashish; Niu, Jiaxin; Lynch, Cynthia A; Farley, John H; Khemka, Vivek

    2017-06-27

    Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy. Patients with advanced, metastatic solid tumours were enrolled onto one of six treatment arms. Pembrolizumab was given: with gemcitabine (G), G+docetaxel (D), G+nab-paclitaxel (NP), G+vinorelbine (V) or irinotecan (I) until progression or toxicity, or with liposomal doxorubicin (LD) for up to 15 cycles, progression or toxicity. Safety monitoring and response assessments were conducted. Forty-nine patients were enrolled and treated. The most common adverse events were transaminitis, cytopenias, rash, diarrhoea, fatigue, nausea and vomiting. Arm 2 was closed due to poor accrual. The recommended phase II dose (RP2D) was determined for Arms 1, 3a, 4, 5 and 6. There were eight partial responses across multiple tumour types. Standard dose P can be safely combined with G, G+NP, G+V, I and LD. Efficacy was observed in multiple tumour types and evaluation to determine if response and duration of response are more robust than what would be expected for chemotherapy or immunotherapy alone requires further validation.

  11. Phase 1 environmental report for the Advanced Neutron Source at Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Blasing, T.J.; Brown, R.A.; Cada, G.F.; Easterly, C.; Feldman, D.L.; Hagan, C.W.; Harrington, R.M.; Johnson, R.O.; Ketelle, R.H.; Kroodsma, R.L.; McCold, L.N.; Reich, W.J.; Scofield, P.A.; Socolof, M.L.; Taleyarkhan, R.P.; Van Dyke, J.W.

    1992-02-01

    The US Department of Energy (DOE) has proposed the construction and operation of the Advanced Neutron Source (ANS), a 330-MW(f) reactor, at Oak Ridge National Laboratory (ORNL) to support neutron scattering and nuclear physics experiments. ANS would provide a steady-state source of neutrons that are thermalized to produce sources of hot, cold, and very coal neutrons. The use of these neutrons in ANS experiment facilities would be an essential component of national research efforts in basic materials science. Additionally, ANS capabilities would include production of transplutonium isotopes, irradiation of potential fusion and fission reactor materials, activation analysis, and production of medical and industrial isotopes such as 252 Cf. Although ANS would not require licensing by the US Nuclear Regulatory Commission (NRC), DOE regards the design, construction, and operation of ANS as activities that would produce a licensable facility; that is, DOE is following the regulatory guidelines that NRC would apply if NRC were licensing the facility. Those guidelines include instructions for the preparation of an environmental report (ER), a compilation of available data and preliminary analyses regarding the environmental impacts of nuclear facility construction and operation. The ER, described and outlined in NRC Regulatory Guide 4.2, serves as a background document to facilitate the preparation of environmental impact statements (EISs). Using Regulatory Guide 4.2 as a model, this ANS ER provides analyses and information specific to the ANS site and area that can be adopted (and modified, if necessary) for the ANS EIS. The ER is being prepared in two phases. Phase 1 ER includes many of the data and analyses needed to prepare the EIS but does not include data or analyses of alternate sites or alternate technologies. Phase 2 ER will include the additional data and analyses stipulated by Regulatory Guide 4.2

  12. Phase 1 environmental report for the Advanced Neutron Source at Oak Ridge National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Blasing, T.J.; Brown, R.A.; Cada, G.F.; Easterly, C.; Feldman, D.L.; Hagan, C.W.; Harrington, R.M.; Johnson, R.O.; Ketelle, R.H.; Kroodsma, R.L.; McCold, L.N.; Reich, W.J.; Scofield, P.A.; Socolof, M.L.; Taleyarkhan, R.P.; Van Dyke, J.W.

    1992-02-01

    The US Department of Energy (DOE) has proposed the construction and operation of the Advanced Neutron Source (ANS), a 330-MW(f) reactor, at Oak Ridge National Laboratory (ORNL) to support neutron scattering and nuclear physics experiments. ANS would provide a steady-state source of neutrons that are thermalized to produce sources of hot, cold, and very coal neutrons. The use of these neutrons in ANS experiment facilities would be an essential component of national research efforts in basic materials science. Additionally, ANS capabilities would include production of transplutonium isotopes, irradiation of potential fusion and fission reactor materials, activation analysis, and production of medical and industrial isotopes such as {sup 252}Cf. Although ANS would not require licensing by the US Nuclear Regulatory Commission (NRC), DOE regards the design, construction, and operation of ANS as activities that would produce a licensable facility; that is, DOE is following the regulatory guidelines that NRC would apply if NRC were licensing the facility. Those guidelines include instructions for the preparation of an environmental report (ER), a compilation of available data and preliminary analyses regarding the environmental impacts of nuclear facility construction and operation. The ER, described and outlined in NRC Regulatory Guide 4.2, serves as a background document to facilitate the preparation of environmental impact statements (EISs). Using Regulatory Guide 4.2 as a model, this ANS ER provides analyses and information specific to the ANS site and area that can be adopted (and modified, if necessary) for the ANS EIS. The ER is being prepared in two phases. Phase 1 ER includes many of the data and analyses needed to prepare the EIS but does not include data or analyses of alternate sites or alternate technologies. Phase 2 ER will include the additional data and analyses stipulated by Regulatory Guide 4.2.

  13. A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

    OpenAIRE

    Chitapanarux, Imjai; Chomprasert, Kittisak; Nobnaop, Wannapa; Wanwilairat, Somsak; Tharavichitkul, Ekasit; Jakrabhandu, Somvilai; Onchan, Wimrak; Traisathit, Patrinee; Van Gestel, Dirk

    2015-01-01

    The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan w...

  14. Prognostic significance of tissue polypeptidespecific antigen (TPS) in patients with advanced non-small cell lung cancer

    NARCIS (Netherlands)

    A. van der Gaast (Ate); C.H.H. Schoenmakers (Christian); T.C. Kok (Tjebbe); B.G. Blijenberg (Bert); W.C.J. Hop (Wim); T.A.W. Splinter (Ted)

    1994-01-01

    textabstractIn this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate

  15. Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

    Science.gov (United States)

    George, Angela; Kristeleit, Rebecca; Rafii, Saeed; Michie, Caroline O; Bowen, Rebecca; Michalarea, Vasiliki; van Hagen, Tom; Wong, Mabel; Rallis, Grigorios; Molife, L Rhoda; Lopez, Juanita; Banerji, Udai; Banerjee, Susana N; Gore, Martin E; de Bono, Johann S; Kaye, Stan B; Yap, Timothy A

    2017-05-01

    Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010. A total of 200 AOC patients with progressive disease were allocated to ≥1 trial each, with a total of 281 allocations. Of these, 135 (68%) patients commenced ≥1 trial (mean 1.4 [1-8]), totaling 216 allocated trials; 65 (32%) patients did not start due to deterioration resulting from rapidly progressive disease (63 patients) or patient choice (2 patients). Response Evaluation Criteria in Solid Tumours (RECIST) complete/partial responses (CR/PR) were observed in 43 (20%) of those starting trials, including those on poly(ADP-ribose) polymerase (PARP) inhibitors (18/79 [23%]), antiangiogenics (9/65 [14%]) and chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR included: fewer prior treatments, platinum-sensitive disease, CR/PR with prior therapy, (the United States-based) Eastern Cooperative Oncology Group (ECOG) performance status score, fewer metastatic sites, higher albumin and haemoglobin levels, lower white cell counts and baseline CA125 levels, germline BRCA1/2 mutations and better RMH Prognostic Score. Mean survival was 32° months for patients who achieved CR/PR. Treatments were generally well tolerated. Most patients with AOC (134/200 [67%]) received ≥1 subsequent line of therapy after phase I trials. Our data suggest that phase I trial referrals should be considered earlier in the AOC treatment pathway and before the onset of rapid disease progression particularly with the emergence of

  16. Characterization and Suppression of the Electromagnetic Interference Induced Phase Shift in the JLab FEL Photo - Injector Advanced Drive Laser System

    Energy Technology Data Exchange (ETDEWEB)

    F. G. Wilson, D. Sexton, S. Zhang

    2011-09-01

    The drive laser for the photo-cathode gun used in the JLab Free Electron Laser (FEL) facility had been experiencing various phase shifts on the order of tens of degrees (>20{sup o} at 1497 MHz or >40ps) when changing the Advanced Drive Laser (ADL) [2][3][4] micro-pulse frequencies. These phase shifts introduced multiple complications when trying to setup the accelerator for operation, ultimately inhibiting the robustness and overall performance of the FEL. Through rigorous phase measurements and systematic characterizations, we determined that the phase shifts could be attributed to electromagnetic interference (EMI) coupling into the ADL phase control loop, and subsequently resolved the issue of phase shift to within tenths of a degree (<0.5{sup o} at 1497 MHz or <1ps). The diagnostic method developed and the knowledge gained through the entire process will prove to be invaluable for future designs of similar systems.

  17. Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer.

    Science.gov (United States)

    Choueiri, Toni K; Plimack, Elizabeth; Arkenau, Hendrik-Tobias; Jonasch, Eric; Heng, Daniel Y C; Powles, Thomas; Frigault, Melanie M; Clark, Edwin A; Handzel, Amir A; Gardner, Humphrey; Morgan, Shethah; Albiges, Laurence; Pal, Sumanta Kumar

    2017-09-10

    Purpose Patients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status. Patients and Methods Patients with histologically confirmed locally advanced or metastatic PRCC were enrolled and received savolitinib 600 mg orally once daily. MET-driven PRCC was defined as any of the following: chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations. Efficacy was assessed according to MET status. Safety, toxicity, and patient-reported health-related quality-of-life outcomes were assessed in all patients. Results Of 109 patients treated, PRCC was MET driven in 44 (40%) and MET independent in 46 (42%); MET status was unknown in 19 (17%). MET-driven PRCC was strongly associated with response; there were eight confirmed partial responders with MET-driven disease (18%), but none with MET-independent disease ( P = .002). Median progression-free survival for patients with MET-driven and MET-independent PRCC was 6.2 months (95% CI, 4.1 to 7.0 months) and 1.4 months (95% CI, 1.4 to 2.7 months), respectively (hazard ratio, 0.33; 95% CI, 0.20 to 0.52; log-rank P < .001). The most frequent adverse events associated with savolitinib were nausea, fatigue, vomiting, and peripheral edema. Conclusion These data show activity and tolerability of savolitinib in the subgroup of patients with MET-driven PRCC. Furthermore, molecular characterization of MET status was more predictive of response to savolitinib than a classification based on pathology. These findings justify investigating savolitinib in MET-driven PRCC.

  18. Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

    Science.gov (United States)

    Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

    2014-07-01

    Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

  19. Phase I dose escalating trial of hyperfractinated pre-operative chemoradiation for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Movsas, Benjamin; Hanlon, Alexandra L.; Lanciano, Rachelle M.; Scher, Richard M.; Weiner, Louis M.; Sigurdson, Elin R.; Hoffman, John P.; Cooper, Harry S.; Provins, Susan; Coia, Lawrence R.

    1997-01-01

    ). CONCLUSION: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p 2 04). This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting

  20. Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

    Energy Technology Data Exchange (ETDEWEB)

    Caravatta, Luciana [Department of Radiation Oncology, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Padula, Gilbert D.A. [Department of Radiation Oncology, Lacks Cancer Center Saint Mary' s Health Care, Grand Rapids, MI (United States); Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it [Department of Radiation Oncology, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Ferrandina, Gabriella [Department of Gynecologic Oncology, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Bonomo, Pierluigi; Deodato, Francesco; Massaccesi, Mariangela [Department of Radiation Oncology, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Mignogna, Samantha; Tambaro, Rosa [Department of Palliative Therapies, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Rossi, Marco [Department of Anaesthesia, Intensive Care, and Pain Medicine, Fondazione di Ricercae Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Flocco, Mariano [' Madre Teresa di Calcutta' Hospice, Larino (Italy); Scapati, Andrea [Department of Radiation Oncology, ' San Francesco' Hospital, Nuoro (Italy); and others

    2012-08-01

    Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of {<=}3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

  1. Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

    International Nuclear Information System (INIS)

    Caravatta, Luciana; Padula, Gilbert D.A.; Macchia, Gabriella; Ferrandina, Gabriella; Bonomo, Pierluigi; Deodato, Francesco; Massaccesi, Mariangela; Mignogna, Samantha; Tambaro, Rosa; Rossi, Marco; Flocco, Mariano; Scapati, Andrea

    2012-01-01

    Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of ≤3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

  2. Phase I study of conformal radiotherapy with concurrent gemcitabine in locally advanced bladder cancer

    International Nuclear Information System (INIS)

    Sangar, Vijay K.; McBain, Catherine A.; Lyons, Jeanette; Ramani, Vijay; Logue, John; Wylie, James; Clarke, Noel W.; Cowan, Richard A.

    2005-01-01

    Purpose: A prospective phase I trial was conducted to determine the maximal tolerated dose of gemcitabine given once weekly during hypofractionated conformal radiotherapy to patients with locally advanced transitional cell carcinoma of the bladder. Eight male patients, median age 69 years, with Stage T2 (n = 4) or T3 (n = 4) N0M0, were enrolled in cohorts of 3. Treatment comprised conformal radiotherapy (52.5 Gy in 20 fractions) within 4 weeks, with concurrent gemcitabine once weekly for four cycles. The weekly gemcitabine dose was escalated from 100 mg/m 2 in increments of 50 mg/m 2 per cohort. Dose-limiting toxicity was defined as any acute Radiation Therapy Oncology Group (RTOG) toxicity Grade 3 or greater arising in >1 of 3 patients in each cohort. Tumor response was assessed cystoscopically and radiologically at 3 months. Results: All 8 patients completed radiotherapy, and 6 of 8 completed chemoradiotherapy. No acute toxicity greater than RTOG Grade 1 was seen with gemcitabine at 100 mg/m 2 . Dose-limiting toxicity was observed at 150 mg/m 2 with Grade 3 toxicity seen in 2 of 2 patients (one bladder, one bowel). An additional 3 patients received 100 mg/m 2 with minimal toxicity. No hematologic toxicity was encountered. A complete response was seen in 7 (87.5%) of 8 patients, all of whom were disease free at a median follow-up of 19.5 months (range, 14-23 months). No late toxicity (greater than RTOG Grade 0) has been observed. Conclusion: The maximal tolerated dose for gemcitabine given once weekly with concurrent hypofractionated conformal bladder radiotherapy was 150 mg/m 2 , with a maximal recommended dose of 100 mg/m 2 . This dose regimen has now entered Phase II clinical trials

  3. Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial.

    Science.gov (United States)

    Gulec, Seza A; Cohen, Steven J; Pennington, Kenneth L; Zuckier, Lionel S; Hauke, Ralph J; Horne, Heather; Wegener, William A; Teoh, Nick; Gold, David V; Sharkey, Robert M; Goldenberg, David M

    2011-06-15

    Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer. Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). (111)In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before (90)Y-hPAM4; otherwise, 20 patients received (90)Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with (90)Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated (90)Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer. ©2011 AACR.

  4. Advanced phase change materials and systems for solar passive heating and cooling of residential buildings

    Energy Technology Data Exchange (ETDEWEB)

    Salyer, I.O.; Sircar, A.K.; Dantiki, S.

    1988-01-01

    During the last three years under the sponsorship of the DOE Solar Passive Division, the University of Dayton Research Institute (UDRI) has investigated four phase change material (PCM) systems for utility in thermal energy storage for solar passive heating and cooling applications. From this research on the basis of cost, performance, containment, and environmental acceptability, we have selected as our current and most promising series of candidate phase change materials, C-15 to C-24 linear crystalline alkyl hydrocarbons. The major part of the research during this contract period was directed toward the following three objectives. Find, test, and develop low-cost effective phase change materials (PCM) that melt and freeze sharply in the comfort temperature range of 73--77{degree}F for use in solar passive heating and cooling of buildings. Define practical materials and processes for fire retarding plasterboard/PCM building products. Develop cost-effective methods for incorporating PCM into building construction materials (concrete, plasterboard, etc.) which will lead to the commercial manufacture and sale of PCM-containing products resulting in significant energy conservation.

  5. Testing earthquake prediction algorithms: Statistically significant advance prediction of the largest earthquakes in the Circum-Pacific, 1992-1997

    Science.gov (United States)

    Kossobokov, V.G.; Romashkova, L.L.; Keilis-Borok, V. I.; Healy, J.H.

    1999-01-01

    Algorithms M8 and MSc (i.e., the Mendocino Scenario) were used in a real-time intermediate-term research prediction of the strongest earthquakes in the Circum-Pacific seismic belt. Predictions are made by M8 first. Then, the areas of alarm are reduced by MSc at the cost that some earthquakes are missed in the second approximation of prediction. In 1992-1997, five earthquakes of magnitude 8 and above occurred in the test area: all of them were predicted by M8 and MSc identified correctly the locations of four of them. The space-time volume of the alarms is 36% and 18%, correspondingly, when estimated with a normalized product measure of empirical distribution of epicenters and uniform time. The statistical significance of the achieved results is beyond 99% both for M8 and MSc. For magnitude 7.5 + , 10 out of 19 earthquakes were predicted by M8 in 40% and five were predicted by M8-MSc in 13% of the total volume considered. This implies a significance level of 81% for M8 and 92% for M8-MSc. The lower significance levels might result from a global change in seismic regime in 1993-1996, when the rate of the largest events has doubled and all of them become exclusively normal or reversed faults. The predictions are fully reproducible; the algorithms M8 and MSc in complete formal definitions were published before we started our experiment [Keilis-Borok, V.I., Kossobokov, V.G., 1990. Premonitory activation of seismic flow: Algorithm M8, Phys. Earth and Planet. Inter. 61, 73-83; Kossobokov, V.G., Keilis-Borok, V.I., Smith, S.W., 1990. Localization of intermediate-term earthquake prediction, J. Geophys. Res., 95, 19763-19772; Healy, J.H., Kossobokov, V.G., Dewey, J.W., 1992. A test to evaluate the earthquake prediction algorithm, M8. U.S. Geol. Surv. OFR 92-401]. M8 is available from the IASPEI Software Library [Healy, J.H., Keilis-Borok, V.I., Lee, W.H.K. (Eds.), 1997. Algorithms for Earthquake Statistics and Prediction, Vol. 6. IASPEI Software Library]. ?? 1999 Elsevier

  6. Significant renoprotective effect of telbivudine during preemptive antiviral therapy in advanced liver cancer patients receiving cisplatin-based chemotherapy: a case-control study.

    Science.gov (United States)

    Lin, Chih-Lang; Chien, Rong-Nan; Yeh, Charisse; Hsu, Chao-Wei; Chang, Ming-Ling; Chen, Yi-Cheng; Yeh, Chau-Ting

    2014-12-01

    Cisplatin is a known nephrotoxic agent requiring vigorous hydration before use. However, aggressive hydration could be life-threatening. Therefore, in cirrhotic patients with advanced hepatocellular carcinoma (HCC) under cisplatin-based chemotherapy, the risk of nephrotoxicity increased. Because previous studies showed that long-term telbivudine treatment improved renal function in chronic hepatitis B virus (HBV) infected patients, we conducted a case-control study to evaluate the clinical outcome of telbivudine preemptive therapy in HBV-related advanced HCC patients treated by combination chemotherapy comprising 5-fluorouracil, mitoxantrone and cisplatin (FMP). From June 2007 to March 2012, 60 patients with HBV-related advanced HCC, all receiving the same FMP chemotherapy protocol, were enrolled. Of them, 20 did not receive any antiviral therapy, whereas the remaining 40 patients (sex and age matched) received telbivudine preemptive therapy. Progressive decrease of aminotransferase levels (p 100 ml/min (n = 34), the median overall survival was significantly longer in the telbivudine-treated group (12.1 vs. 4.9 months; p = 0.042). Preemptive use of telbivudine significantly prevented eGFR deterioration caused by cisplatin-based chemotherapy in HBV-related advanced HCC. In patients with initially sufficient eGFR level, telbivudine treatment was associated with a longer overall survival.

  7. Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma

    DEFF Research Database (Denmark)

    Maughan, Benjamin L; Agarwal, Neeraj; Hussain, Syed A

    2013-01-01

    Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC an...

  8. Phase I trial of neoadjuvant concurrent chemoradiotherapy with S-1 and weekly irinotecan in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Choi, Hye Jin; Kim, Nam-Kyu; Keum, Ki Chang; Cheon, Seong Ha; Shin, Sang Jun; Baik, Seung Hyuk; Choen, Jae Hee; Rha, Sun Young; Roh, Jae Kyung; Jeung, Hei-Cheul; Chung, Hyun Cheol; Ahn, Joong Bae

    2008-01-01

    S-1 is a novel, oral fluoropyrimidine and a known radiosensitizer. We conducted a phase I trial to establish a schedule of S-1/irinotecan with standard pelvic radiotherapy as a preoperative treatment of locally advanced rectal cancer. Our findings suggest that this new combination is feasible and well tolerable

  9. Advanced fabrication method for the preparation of MOF thin films: Liquid-phase epitaxy approach meets spin coating method.

    KAUST Repository

    Chernikova, Valeriya; Shekhah, Osama; Eddaoudi, Mohamed

    2016-01-01

    Here we report a new and advanced method for the fabrication of highly oriented/polycrystalline metal-organic framework (MOF) thin films. Building on the attractive features of the liquid-phase epitaxy (LPE) approach, a facile spin coating method

  10. Advanced Si solid phase crystallization for vertical channel in vertical NANDs

    Directory of Open Access Journals (Sweden)

    Sangsoo Lee

    2014-07-01

    Full Text Available The advanced solid phase crystallization (SPC method using the SiGe/Si bi-layer structure is proposed to obtain high-mobility poly-Si thin-film transistors in next generation vertical NAND (VNAND devices. During the SPC process, the top SiGe thin film acts as a selective nucleation layer to induce surface nucleation and equiaxial microstructure. Subsequently, this SiGe thin film microstructure is propagated to the underlying Si thin film by epitaxy-like growth. The initial nucleation at the SiGe surface was clearly observed by in situ transmission electron microscopy (TEM when heating up to 600 °C. The equiaxial microstructures of both SiGe nucleation and Si channel layers were shown in the crystallized bi-layer plan-view TEM measurements. Based on these experimental results, the large-grained and less-defective Si microstructure is expected to form near the channel region of each VNAND cell transistor, which may improve the electrical characteristics.

  11. Limitations of the Conventional Phase Advance Method for Constant Power Operation of the Brushless DC Motor

    International Nuclear Information System (INIS)

    Lawler, J.S.

    2001-01-01

    The brushless dc motor (BDCM) has high-power density and efficiency relative to other motor types. These properties make the BDCM well suited for applications in electric vehicles provided a method can be developed for driving the motor over the 4 to 6:1 constant power speed range (CPSR) required by such applications. The present state of the art for constant power operation of the BDCM is conventional phase advance (CPA)[1]. In this paper, we identify key limitations of CPA. It is shown that the CPA has effective control over the developed power but that the current magnitude is relatively insensitive to power output and is inversely proportional to motor inductance. If the motor inductance is low, then the rms current at rated power and high speed may be several times larger than the current rating. The inductance required to maintain rms current within rating is derived analytically and is found to be large relative to that of BDCM designs using high-strength rare earth magnets. Th us, the CPA requires a BDCM with a large equivalent inductance

  12. Celecoxib plus chemoradiotherapy for locally advanced rectal cancer: a phase II TCOG study.

    Science.gov (United States)

    Wang, Ling-Wei; Hsiao, Chin-Fu; Chen, William Tzu-Liang; Lee, Hao-Hsien; Lin, Tzu-Chen; Chen, Hung-Chang; Chen, Hong-Hwa; Chien, Chun-Ru; Lin, Tze-Yi; Liu, Tsang-Wu

    2014-05-01

    To report the results of a phase II trial combining celecoxib and preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Patients with clinical stage II or III rectal cancer were treated with radiotherapy of 44 Gy in 22 fractions. Concurrent chemotherapy consisted of oral tegafur-uracil and folinate on days 1-30 and 38-65. Celecoxib (400 mg/day) given from days 1 to 65. Surgery was done on day 70. The expression of cyclooxygenase 2 (COX-2) in tumor tissues was evaluated microscopically as a prognostic factor. From 2008 to 2011, 53 patients completed CRT+ celecoxib therapy and 47 received radical surgery. Grade 3 diarrhea developed in 5 (9%). Grade 4 anemia was seen in 2 (4%). Pathological complete response (pCR) was seen in 6 (13%). T or N downstaging found in 38 (81%). Sphincter preservation was achieved in 77% of low-positioned tumors. Patients with tumors expressing high-level COX-2 after CRT + celecoxib treatment had inferior pelvic control (P = 0.01), disease-free survival (P = 0.04), and overall survival (P = 0.03) than those with low-level expression. Celecoxib can be safely combined with preoperative CRT for rectal cancer. More intensified adjuvant therapy may be considered for tumors expressing high-level COX-2 after CRT and surgery. © 2013 Wiley Periodicals, Inc.

  13. Advanced supersonic propulsion study, phase 2. [propulsion system performance, design analysis and technology assessment

    Science.gov (United States)

    Howlett, R. A.

    1975-01-01

    A continuation of the NASA/P and WA study to evaluate various types of propulsion systems for advanced commercial supersonic transports has resulted in the identification of two very promising engine concepts. They are the Variable Stream Control Engine which provides independent temperature and velocity control for two coannular exhaust streams, and a derivative of this engine, a Variable Cycle Engine that employs a rear flow-inverter valve to vary the bypass ratio of the cycle. Both concepts are based on advanced engine technology and have the potential for significant improvements in jet noise, exhaust emissions and economic characteristics relative to current technology supersonic engines. Extensive research and technology programs are required in several critical areas that are unique to these supersonic Variable Cycle Engines to realize these potential improvements. Parametric cycle and integration studies of conventional and Variable Cycle Engines are reviewed, features of the two most promising engine concepts are described, and critical technology requirements and required programs are summarized.

  14. Effects of hard mask etch on final topography of advanced phase shift masks

    Science.gov (United States)

    Hortenbach, Olga; Rolff, Haiko; Lajn, Alexander; Baessler, Martin

    2017-07-01

    Continuous shrinking of the semiconductor device dimensions demands steady improvements of the lithographic resolution on wafer level. These requirements challenge the photomask industry to further improve the mask quality in all relevant printing characteristics. In this paper topography of the Phase Shift Masks (PSM) was investigated. Effects of hard mask etch on phase shift uniformity and mask absorber profile were studied. Design of experiments method (DoE) was used for the process optimization, whereas gas composition, bias power of the hard mask main etch and bias power of the over-etch were varied. In addition, influence of the over-etch time was examined at the end of the experiment. Absorber depth uniformity, sidewall angle (SWA), reactive ion etch lag (RIE lag) and through pitch (TP) dependence were analyzed. Measurements were performed by means of Atomic-force microscopy (AFM) using critical dimension (CD) mode with a boot-shaped tip. Scanning electron microscope (SEM) cross-section images were prepared to verify the profile quality. Finally CD analysis was performed to confirm the optimal etch conditions. Significant dependence of the absorber SWA on hard mask (HM) etch conditions was observed revealing an improvement potential for the mask absorber profile. It was found that hard mask etch can leave a depth footprint in the absorber layer. Thus, the etch depth uniformity of hard mask etch is crucial for achieving a uniform phase shift over the active mask area. The optimized hard mask etch process results in significantly improved mask topography without deterioration of tight CD specifications.

  15. Advanced Nanostructured Cathode for Ultra High Specific Energy Lithium Ion Batteries, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Integrate advanced nanotechnology with energy storage technology to develop advanced cathode materials for use in Li-ion batteries while maintaining a high level of...

  16. Significant effect of substrate temperature on the phase structure, optical and electrical properties of RF sputtered CIGS films

    Energy Technology Data Exchange (ETDEWEB)

    Yu Zhou; Yan Yong; Li Shasha; Zhang Yanxia; Yan Chuanpeng; Liu Lian; Zhang Yong [Key Laboratory of Magnetic Suspension Technology and Maglev Vehicle, Ministry of Education, Superconductivity and New energy R and D Center (SNERDC), Mail Stop 165, Southwest Jiaotong University, Chengdu 610031 (China); Zhao Yong, E-mail: yzhao@swjtu.edu.cn [Key Laboratory of Magnetic Suspension Technology and Maglev Vehicle, Ministry of Education, Superconductivity and New energy R and D Center (SNERDC), Mail Stop 165, Southwest Jiaotong University, Chengdu 610031 (China); School of Materials Science and Engineering, University of New South Wales, Sydney 2052, NSW (Australia)

    2013-01-01

    Highlights: Black-Right-Pointing-Pointer Secondary phase exist in the RF sputtered CIGS films as it deposited at 150 Degree-Sign C and 500 Degree-Sign C. Black-Right-Pointing-Pointer CIGS films deposited beyond 350 Degree-Sign C show (1 1 2) prefer orientation. Black-Right-Pointing-Pointer E{sub g} of the CIGS films increased with the increase of substrate temperature. Black-Right-Pointing-Pointer Conductivity of the films is affected by 'variable range hopping' mechanism. - Abstract: This work studied the effect of substrate temperature on the phase structure, optical and electrical properties of the one-step radio frequency sputtered Cu(In,Ga)Se{sub 2} (CIGS) thin films. X-ray diffraction (XRD) analysis revealed that all the deposited CIGS films are chalcopyrite phase with polycrystalline structure. The films deposited beyond the substrate temperature of 350 Degree-Sign C show (1 1 2) prefer orientation. Raman spectra reveal that the 150 Degree-Sign C deposited CIGS film coexists with Cu{sub 2-x}Se phase and the 500 Degree-Sign C deposited film contains ordered defect compound (ODC) phase. With the increase of substrate temperature, energy band gap of the CIGS film increase from 0.99 to 1.27 eV. Films deposited at higher temperature exhibit larger electrical conductivity. Conductivity of the CIGS films is dominated by 'variable range hopping' mechanism. The disorder in our CIGS the films is associated with the formation of intrinsic defects such as V{sub Se} and In{sub Cu} for their low formation energy.

  17. SPIRIT trial: A phase III pragmatic trial of an advance care planning intervention in ESRD.

    Science.gov (United States)

    Song, Mi-Kyung; Unruh, Mark L; Manatunga, Amita; Plantinga, Laura C; Lea, Janice; Jhamb, Manisha; Kshirsagar, Abhijit V; Ward, Sandra E

    2018-01-01

    Advance care planning (ACP) is a central tenet of dialysis care, but the vast majority of dialysis patients report never engaging in ACP discussions with their care providers. Over the last decade, we have developed and iteratively tested SPIRIT (Sharing Patient's Illness Representation to Increase Trust), a theory-based, patient- and family-centered advance care planning intervention. SPIRIT is a six-step, two-session, face-to-face intervention to promote cognitive and emotional preparation for end-of-life decision making for patients with ESRD and their surrogates. In these explanatory trials, SPIRIT was delivered by trained research nurses. Findings consistently revealed that patients and surrogates in SPIRIT showed significant improvement in preparedness for end-of-life decision making, and surrogates in SPIRIT reported significantly improved post-bereavement psychological outcomes after the patient's death compared to a no treatment comparison condition. As a critical next step, we are conducting an effectiveness-implementation study. This study is a multicenter, clinic-level cluster randomized pragmatic trial to evaluate the effectiveness of SPIRIT delivered by dialysis care providers as part of routine care in free-standing outpatient dialysis clinics, compared to usual care plus delayed SPIRIT implementation. Simultaneously, we will evaluate the implementation of SPIRIT, including sustainability. We will recruit 400 dyads of patients at high risk of death in the next year and their surrogates from 30 dialysis clinics in four states. This trial of SPIRIT will generate novel, meaningful insights about improving ACP in dialysis care. ClinicalTrials.govNCT03138564, registered 05/01/2017. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial

    International Nuclear Information System (INIS)

    Allal, Abdelkarim S.; Bieri, Sabine; Bruendler, Marie-Anne; Soravia, Claudio; Gertsch, Philippe; Bernier, Jacques; Morel, Philippe; Roth, Arnaud D.

    2002-01-01

    Purpose: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. Methods and Materials: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. Results: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located ≤6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). Conclusion: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a

  19. Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results.

    Science.gov (United States)

    Criner, Gerard J; Pinto-Plata, Victor; Strange, Charlie; Dransfield, Mark; Gotfried, Mark; Leeds, William; McLennan, Geoffrey; Refaely, Yael; Tewari, Sanjiv; Krasna, Mark; Celli, Bartolome

    2009-05-01

    Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling. Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema. Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life. After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4 +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life. BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

  20. On-the-Fly Kinetic Monte Carlo Simulation of Aqueous Phase Advanced Oxidation Processes.

    Science.gov (United States)

    Guo, Xin; Minakata, Daisuke; Crittenden, John

    2015-08-04

    We have developed an on-the-fly kinetic Monte Carlo (KMC) model to predict the degradation mechanisms and fates of intermediates and byproducts that are produced during aqueous-phase advanced oxidation processes (AOPs). The on-the-fly KMC model is composed of a reaction pathway generator, a reaction rate constant estimator, a mechanistic reduction module, and a KMC solver. The novelty of this work is that we develop the pathway as we march forward in time rather than developing the pathway before we use the KMC method to solve the equations. As a result, we have fewer reactions to consider, and we have greater computational efficiency. We have verified this on-the-fly KMC model for the degradation of polyacrylamide (PAM) using UV light and titanium dioxide (i.e., UV/TiO2). Using the on-the-fly KMC model, we were able to predict the time-dependent profiles of the average molecular weight for PAM. The model provided detailed and quantitative insights into the time evolution of the molecular weight distribution and reaction mechanism. We also verified our on-the-fly KMC model for the destruction of (1) acetone, (2) trichloroethylene (TCE), and (3) polyethylene glycol (PEG) for the ultraviolet light and hydrogen peroxide AOP. We demonstrated that the on-the-fly KMC model can achieve the same accuracy as the computer-based first-principles KMC (CF-KMC) model, which has already been validated in our earlier work. The on-the-fly KMC is particularly suitable for molecules with large molecular weights (e.g., polymers) because the degradation mechanisms for large molecules can result in hundreds of thousands to even millions of reactions. The ordinary differential equations (ODEs) that describe the degradation pathways cannot be solved using traditional numerical methods, but the KMC can solve these equations.

  1. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Leone, Robert; Chang, Yunyoung C; Fecher, Leslie A; Schuchter, Lynn M; Kramer, Amy; Tan, Kay-See; Heitjan, Daniel F; Rodgers, Glenda; Gallagher, Maryann; Piao, Shengfu; Troxel, Andrea B; Evans, Tracey L; DeMichele, Angela M; Nathanson, Katherine L; O'Dwyer, Peter J; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; Amaravadi, Ravi K

    2014-08-01

    Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

  2. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O'Dwyer, Peter J; Amaravadi, Ravi K

    2014-08-01

    The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted.

  3. Advanced Start of Combustion Sensor Phases I and II-A: Feasibility Demonstration, Design and Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Chad Smutzer

    2010-01-31

    Homogeneous Compressed Charge Ignition (HCCI) has elevated the need for Start of Combustion (SOC) sensors. HCCI engines have been the exciting focus of engine research recently, primarily because HCCI offers higher thermal efficiency than the conventional Spark Ignition (SI) engines and significantly lower NOx and soot emissions than conventional Compression Ignition (CI) engines, and could be fuel neutral. HCCI has the potential to unify all the internal combustion engine technology to achieve the high-efficiency, low-emission goal. However, these advantages do not come easy. It is well known that the problems encountered with HCCI combustion center on the difficulty of controlling the Start of Combustion. TIAX has an SOC sensor under development which has shown promise. In previous work, including a DOE-sponsored SBIR project, TIAX has developed an accelerometer-based method which was able to determine SOC within a few degrees crank angle for a range of operating conditions. A signal processing protocol allows reconstruction of the combustion pressure event signal imbedded in the background engine vibration recorded by the accelerometer. From this reconstructed pressure trace, an algorithm locates the SOC. This SOC sensor approach is nonintrusive, rugged, and is particularly robust when the pressure event is strong relative to background engine vibration (at medium to high engine load). Phase I of this project refined the previously developed technology with an engine-generic and robust algorithm. The objective of the Phase I research was to answer two fundamental questions: Can the accelerometer-based SOC sensor provide adequate SOC event capture to control an HCCI engine in a feedback loop? And, will the sensor system meet cost, durability, and software efficiency (speed) targets? Based upon the results, the answer to both questions was 'YES'. The objective of Phase II-A was to complete the parameter optimization of the SOC sensor prototype in order

  4. Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

    International Nuclear Information System (INIS)

    Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

    1981-01-01

    Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation

  5. Advanced fabrication method for the preparation of MOF thin films: Liquid-phase epitaxy approach meets spin coating method.

    KAUST Repository

    Chernikova, Valeriya

    2016-07-14

    Here we report a new and advanced method for the fabrication of highly oriented/polycrystalline metal-organic framework (MOF) thin films. Building on the attractive features of the liquid-phase epitaxy (LPE) approach, a facile spin coating method was implemented to generate MOF thin films in a high-throughput fashion. Advantageously, this approach offers a great prospective to cost-effectively construct thin-films with a significantly shortened preparation time and a lessened chemicals and solvents consumption, as compared to the conventional LPE-process. Certainly, this new spin-coating approach has been implemented successfully to construct various MOF thin films, ranging in thickness from a few micrometers down to the nanometer scale, spanning 2-D and 3-D benchmark MOF materials including Cu2(bdc)2•xH2O, Zn2(bdc)2•xH2O, HKUST-1 and ZIF-8. This method was appraised and proved effective on a variety of substrates comprising functionalized gold, silicon, glass, porous stainless steel and aluminum oxide. The facile, high-throughput and cost-effective nature of this approach, coupled with the successful thin film growth and substrate versatility, represents the next generation of methods for MOF thin film fabrication. Thereby paving the way for these unique MOF materials to address a wide range of challenges in the areas of sensing devices and membrane technology.

  6. Update of progress for Phase II of B&W`s advanced coal-fired low-emission boiler system

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, D.K. [Babcock & Wilcox, Barberton, OH (United States); Madden, D.A.; Rodgers, L.W. [Babcock & Wilcox, Alliance, OH (United States)] [and others

    1995-11-01

    Over the past five years, advances in emission control techniques at reduced costs and auxiliary power requirements coupled with significant improvements in steam turbine and cycle design have significantly altered the governing criteria by which advanced technologies have been compared. With these advances, it is clear that pulverized coal technology will continue to be competitive in both cost and performance with other advanced technologies such as Integrated Gasification Combined Cycle (IGCC) or first generation Pressurized Fluidized Bed Combustion (PFBC) technologies for at least the next decade. In the early 1990`s it appeared that if IGCC and PFBC could achieve costs comparable to conventional pulverized coal plants, their significantly reduced NO{sub x} and SO{sub 2} emissions would make them more attractive. A comparison of current emission control capabilities shows that all three technologies can already achieve similarly low emissions levels.

  7. Chemo-radiotherapy plus hyperthermia in locally advanced cervical cancer: preliminary results of an institutional phase II study

    International Nuclear Information System (INIS)

    Gabbani, M.; Marciai, N.; Maluta, S.; Griso, C.; Merlin, F.; Cassandrini, P.; Giudici, S.; Franchi, M.; Zanini, L.

    2005-01-01

    Full text: Radiotherapy given concurrently with a cisplatin-based regimen has shown a benefit in patients with locally advanced cervical cancer so becoming the new standard treatment according to EBM criteria. Addition of hyperthermia to radiotherapy has also been proved to yield an advantage in survival and local control in pts affected by recurrent and local advanced cervical cancer in the Dutch Phase III trial so that the Consensus Forum of Kadota (Osaha June 2004) included cervical cancer among tumors treatable with hyperthermia. In our institutional multidisciplinary team a pilot study has been designed in order to evaluate feasibility, outcome and toxicity of tri-modality treatment in pts with locally advanced cervical cancer in our daily practice. Since January 2003 to now eight patients affected by cervical cancer with stage IB2 through IVA N0-N+ pelvic or paraaortic were entered the study. Six patients were treated at initial diagnosis and two patients after chemotherapy which had achieved stable disease. Treatment regimen consisted in 5 courses of weekly chemotherapy (cisplatin 40 mg/mq) with concurrent external radiotherapy to a total dose of 64-66 Gy on CTV1 and 45 Gy on para-aortic nodes plus boost in pts with enlarged nodes identified by imaging. Five weekly sessions of hyperthermia were performed by using BSD 2000 system and sigma 60 applicator. No significant toxicity occurred and all of the patients completed tri-modality treatment in accordance with the study protocol. Seven pts experienced a complete clinical remission and one patient a partial remission as defined by clinical and imaging examinations. After four months from the end of the treatment a patient with Stage IIB bulky tumor plus one pelvic positive node who was in complete remission (Clinical examination, MRI and TAC-PET three months from the end of the treatment were negative for evidence of disease) developed a bleeding recto-vaginal fistula plus central pelvic necrosis for which an

  8. Lightweight, Efficient Power Converters for Advanced Turboelectric Aircraft Propulsion Systems, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is investigating advanced turboelectric aircraft propulsion systems that utilize superconducting motors to drive a number of distributed turbofans. In an...

  9. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer.

    Science.gov (United States)

    Borad, Mitesh J; Reddy, Shantan G; Bahary, Nathan; Uronis, Hope E; Sigal, Darren; Cohn, Allen L; Schelman, William R; Stephenson, Joe; Chiorean, E Gabriela; Rosen, Peter J; Ulrich, Brian; Dragovich, Tomislav; Del Prete, Salvatore A; Rarick, Mark; Eng, Clarence; Kroll, Stew; Ryan, David P

    2015-05-01

    TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m(2)), gemcitabine plus TH-302 240 mg/m(2) (G+T240), or gemcitabine plus TH-302 340 mg/m(2) (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (-5,398 v -549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302-related AEs but were not associated with treatment discontinuation. PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979). © 2014 by American Society of

  10. Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

    Science.gov (United States)

    Bianco, A; Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Rodriguez, R; Cuevas, M A; Alvarez, L A

    1990-02-28

    Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

  11. Quantitative study on the significance of FR cycle. Interim report of JNC/CEA joint study on advanced technology R and D for nuclear energy

    International Nuclear Information System (INIS)

    Fiorini, G.L.; Shinoda, Yoshihiko; Kofuji, Hirohide; Hirao, Kazunori

    2001-09-01

    This study on quantitative study on significance of FR cycle was carried out under the agreement between JNC and CEA in the field of advanced technology R and D for nuclear energy. JNC has been developing the quantitative evaluation method to be constructed by combining Analytic Hierarchy Process (AHP) and Multi-Attribute Utility Theory (MAUT). CEA has been caring out the qualitative evaluation from expert judgement from viewpoint of sustainability such as the response to the energetic demand, the saving of the resources and the minimization of the environmental impact. (author)

  12. Palliative Radiation Therapy for Advanced Head and Neck Carcinomas: A Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Fortin, Bernard, E-mail: bfortin.hmr@ssss.gouv.qc.ca [Radiation Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec (Canada); Khaouam, Nader [Radiation Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec (Canada); Filion, Edith; Nguyen-Tan, Phuc Felix [Radiation Oncology, Centre Hospitalier de l' Université de Montréal, Montreal, Quebec (Canada); Bujold, Alexis [Radiation Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec (Canada); Lambert, Louise [Radiation Oncology, Centre Hospitalier de l' Université de Montréal, Montreal, Quebec (Canada)

    2016-06-01

    Purpose: Incurable head and neck cancer is hard to manage with usual palliative care. Radiation therapy (RT) in this setting is sometimes omitted because there is an apprehension that the side effects in the head and neck region might counterbalance the benefits. The objective of this phase 2 study was to evaluate whether highly conformal RT could improve the therapeutic ratio with this comprehensive Quality of Life (QOL) and toxicity evaluation. Methods and Materials: Patients from 2 academic centers, deemed unfit for radical treatment because of their poor medical condition or advanced cancer stage by an experienced tumor board, were offered 25 Gy in 5 daily intensity modulated RT fractions over 1 week to the symptomatic tumor volume. QOL was evaluated with the European Organization for Research and Treatment of Cancer QLQ-C15-PAL and QLQ-H&N35 questionnaires, and toxicities with the Common Terminology Criteria for Adverse Events version 4.0. Survival and time to tumor progression were calculated with the Kaplan-Meier method. Results: Thirty-two patients were recruited, of whom 66% had at least T4, N3, or M1 disease. The QOL questionnaires completion rate was 86%. Eighty-eight percent of patients received the planned dose. The median overall survival and progression-free survival times were, respectively, 6.5 and 3.2 months. No grade 4 or 5 toxicity was seen. Only 13% of patients had any grade 3 toxicities, and 17% of patients reported no toxicity at all. The QOL was equal or improved, and head and neck symptoms remained equal to or lower than the baseline values for most patients at up to 6 months. Eighty-five percent of patients would have chosen to receive this RT regimen again when asked. Conclusions: This palliative RT regimen was highly tolerable and effective in preserving or improving self-reported QOL in most patients for up to 6 months, which corresponds to this population's median overall survival. Given the minimal side effects

  13. Benchmarking of thermalhydraulic loop models for lead-alloy-cooled advanced nuclear energy systems. Phase I: Isothermal forced convection case

    International Nuclear Information System (INIS)

    2012-06-01

    Under the auspices of the NEA Nuclear Science Committee (NSC), the Working Party on Scientific Issues of the Fuel Cycle (WPFC) has been established to co-ordinate scientific activities regarding various existing and advanced nuclear fuel cycles, including advanced reactor systems, associated chemistry and flowsheets, development and performance of fuel and materials and accelerators and spallation targets. The WPFC has different expert groups to cover a wide range of scientific issues in the field of nuclear fuel cycle. The Task Force on Lead-Alloy-Cooled Advanced Nuclear Energy Systems (LACANES) was created in 2006 to study thermal-hydraulic characteristics of heavy liquid metal coolant loop. The objectives of the task force are to (1) validate thermal-hydraulic loop models for application to LACANES design analysis in participating organisations, by benchmarking with a set of well-characterised lead-alloy coolant loop test data, (2) establish guidelines for quantifying thermal-hydraulic modelling parameters related to friction and heat transfer by lead-alloy coolant and (3) identify specific issues, either in modelling and/or in loop testing, which need to be addressed via possible future work. Nine participants from seven different institutes participated in the first phase of the benchmark. This report provides details of the benchmark specifications, method and code characteristics and results of the preliminary study: pressure loss coefficient and Phase-I. A comparison and analysis of the results will be performed together with Phase-II

  14. Growth of AlGaN under the conditions of significant gallium evaporation: phase separation and enhanced lateral growth

    OpenAIRE

    Mayboroda, I. O.; Knizhnik, A. A.; Grishchenko, Yu. V.; Ezubchenko, I. S.; Zanaveskin, Maxim L.; Presniakov, M. Yu.; Potapkin, B. V.; Ilyin, V. A.

    2017-01-01

    Growth kinetics of AlGaN in NH3 MBE under significant Ga desorption was studied. It was found that the addition of gallium stimulates 2D growth and provides better morphology of films compared to pure AlN. The effect was experimentally observed at up to 98% desorption of the impinging gallium. We found that, under the conditions of significant thermal desorption, larger amounts of gallium were retained at lateral boundaries of 3D surface features than at flat terraces because of the higher bi...

  15. Capecitabine, oxaliplatin and radiotherapy: Results of the phase II study in locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Torres, M.

    2010-01-01

    postoperative). Conclusions: Our results for the TSO are similar to those of the international bibliography but with significant toxicity that we consider unacceptable. Phase III essays completed (ACCORD 12/0405, STAR-01, GCR-3) confirmed that the addition of oxaliplatin to 5-FU or Capecitabine in conjunction with radiation therapy do not increase the complete pathological responses but significantly it increases severe toxicity so emphatically discouraged use of preoperative oxaliplatin in adjuvant. At present it is considered that 5-FU continuous infusion or Capecitabine associated with radiotherapy is the standard treatment minimum in this therapeutic segment

  16. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Hamid Omid

    2011-11-01

    Full Text Available Abstract Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365, 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014 and indoleamine 2,3-dioxygenase (p = 0.012, and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs between baseline and 3 weeks after start of treatment (p = 0.005. Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with

  17. UTILITY ADVANCED TURBINE SYSTEMS (ATS) TECHNOLOGY READINESS TESTING PHASE 3 RESTRUCTURED (3R)

    Energy Technology Data Exchange (ETDEWEB)

    Unknown

    2000-03-17

    This scope document defines the work scope for accomplishing the design of the GE MS7001H and MS9001H (7H and 9H) combined-cycle power systems under the original ATS Phase 3 DOE Cooperative Agreement No. DE-FC21-95MC31176, and incorporates changes in scope required to convert Phase 3 to the ''restructured'' Phase 3R as defined in Amendment A012 to the Cooperative Agreement.

  18. Advanced Durable Flexible Ultra Low Outgassing Thermal Control Coatings for NASA Science Missions, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This Phase I program proposes to synthesize novel nanoengineered ultra low out gassing elastomers and formulate high temperature capable flexible thermal control...

  19. Biotemplated Nano-Structured Materials for Advanced Li-ion Batteries, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA has identified a critical need for pioneering advances in battery technology to give high performance, low-weight, durable and long-life power sources for...

  20. Deep UV Semiconductor Sources for Advanced Planetary Science Instruments, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposal addresses the need for miniature, narrow-linewidth, deep UV optical sources that operate at very low ambient temperatures for use in advanced in situ...

  1. Advanced Cathode Material For High Energy Density Lithium-Batteries, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced cathode materials having high red-ox potential and high specific capacity offer great promise to the development of high energy density lithium-based...

  2. Advanced Optical Metrology for XRAY Replication Mandrels and Mirrors, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced x-ray observatories such as IXO and GenX will require thousands of thin shell mirror segments produced by replication using convex mandrels. Quality and...

  3. Space Station Validation of Advanced Radiation-Shielding Polymeric Materials, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In Subtopic X11.01, NASA has identified the need to develop advanced radiation-shielding materials and systems to protect humans from the hazards of space radiation...

  4. Advanced Air Evaporation System with Reusable Wicks for Water Recovery, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — A microgravity-compatible Advanced Air Evaporation System (AAES) is proposed for recovering nearly 100% of water from highly contaminated wastewater without concern...

  5. Nucleosynthesis in advanced phases of stellar evolution: comparison between theory and observation

    International Nuclear Information System (INIS)

    Pacheco, J.A.F.

    1990-01-01

    The contamination of stellar atmospheres in advanced stages of evolution is studied, comparing observable data with theoretical expectations. The observable contaminations in some specific stars are presented. (M.C.K.)

  6. High Efficiency Advanced Lightweight Fuel Cell (HEAL-FC), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Infinity's High Efficiency Advanced Lightweight Fuel Cell (HEAL FC) is an improved version of its current fuel cell technology developed for space applications. The...

  7. Advanced Solid-State Joining Processes for 2219 Aluminum Alloys, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Thermal Stir Welding (TSW) advances the more conventional Friction Stir Welding (C-FSW) process by separating the primary process variables of metal stirring and...

  8. Advanced Product Water Removal and Management (APWR) Fuel Cell System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a passive, self-regulating, gravity-independent Advanced Product Water Removal and management (APWR) system for incorporation into Polymer...

  9. Advanced Product Water Removal and Management (APWR) Fuel Cell System, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a passive, self-regulating, gravity-independent Advanced Product Water Removal (APWR) system for Polymer Electrolyte Membrane (PEM)...

  10. Development of Advanced Anti-Reflection Coatings for High Performance Solar Energy Applications, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — MicroLink Devices will increase the efficiency of multi-junction solar cells by designing and demonstrating advanced anti-reflection coatings (ARCs) that will...

  11. Development of Advanced Anti-Reflection Coatings for High Performance Solar Energy Applications, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — MicroLink and its subcontractor Magnolia Solar will develop and demonstrate advanced anti-reflection coating (ARC) designs that will provide a better broadband and...

  12. Phase 1 Study of CK-301 as a Single Agent in Subjects With Advanced Cancers

    Science.gov (United States)

    2018-01-02

    Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Malignant Mesothelioma, Advanced; Head and Neck Cancer; Melanoma; Merkel Cell Carcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Classical Hodgkin Lymphoma

  13. Metal Advanced Manufacturing Bot-Assisted Assembly (MAMBA) Process, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Tethers Unlimited, Inc. (TUI) proposes to develop the Metal Advanced Manufacturing Bot-Assisted Assembly (MAMBA) Process, a robotically managed metal press and...

  14. Non-Intrusive, Distributed Gas Sensing Technology for Advanced Spacesuits, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Advances in spacesuits are required to support the ISS and future human exploration. Spacesuit development and ground-based testing tasks require sensing and...

  15. Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Cardin, Dana B; Goff, Laura; Li, Chung-I; Shyr, Yu; Winkler, Charles; DeVore, Russell; Schlabach, Larry; Holloway, Melanie; McClanahan, Pam; Meyer, Krista; Grigorieva, Julia; Berlin, Jordan; Chan, Emily

    2014-01-01

    This trial was designed to assess efficacy and safety of erlotinib with sorafenib in the treatment of patients with advanced pancreatic adenocarcinoma. An exploratory correlative study analyzing pretreatment serum samples using a multivariate protein mass spectrometry-based test (VeriStrat®), previously shown to correlate with outcomes in lung cancer patients treated with erlotinib, was performed. Patients received sorafenib 400 mg daily along with erlotinib 150 mg daily with a primary endpoint of 8-week progression free survival (PFS) rate. Pretreatment serum sample analysis by VeriStrat was done blinded to clinical and outcome data; the endpoints were PFS and overall survival (OS). Difference between groups (by VeriStrat classification) was assessed using log-rank P values; hazard ratios (HR) were obtained from Cox proportional hazards model. Thirty-six patients received study drug and were included in the survival analysis. Eight-week PFS rate of 46% (95% confidence interval (CI): 0.32–0.67) did not meet the primary endpoint of a rate ≥70%. Thirty-two patients were included in the correlative analysis, and VeriStrat “Good” patients had superior PFS (HR = 0.18, 95% CI: 0.06–0.57; P = 0.001) and OS (HR = 0.31 95% CI: 0.13–0.77, P = 0.008) compared to VeriStrat “Poor” patients. Grade 3 toxicities of this regimen included fever, anemia, diarrhea, dehydration, rash, and altered liver function. This study did not meet the primary endpoint, and this combination will not be further pursued. In this small retrospective analysis, the proteomic classification was significantly associated with clinical outcomes and is being further evaluated in ongoing studies

  16. Animal-vehicle crash mitigation using advanced technology : phase II, system effectiveness and system acceptance.

    Science.gov (United States)

    2009-03-01

    This project was initiated in the fall of 1999. The results through the fall of 2005 (Phase I) have been documented in detail in an earlier report. The accomplishments of Phase I included the following: the identification of existing animal detection...

  17. Fundamental Studies on Phase Transformations and Mechanical Properties of Fusion Welds in Advanced Naval Steels

    Science.gov (United States)

    2017-07-31

    naval and structural applications. However, prior to this research project, a fundamental understanding of the phase transformation behavior under the...prior to this research project, a fundamental understanding of the phase transformation behavior under the high heating and cooling rates associated...HAZ mechanical properties. Such a treatment is expensive, time consuming , and cannot be practically applied to large structures. However, the absence

  18. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

    Science.gov (United States)

    Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

    1998-01-01

    The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

  19. Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Cellier, Patrice; Burtin, Pascal; Campion, Loïc; Boisdron-Celle, Michèle; Morel, Alain; Berger, Virginie; Gamelin, Erick; Leduc, Bernard; Martin, Laurent; Vié, Brigitte; Chevelle, Christian; Vendrely, Véronique; Salemkour, Augustin; Carrie, Christian; Calais, Gilles

    2011-01-01

    Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment. This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/ 2 /day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate. Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (DPYD) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66

  20. Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

    Science.gov (United States)

    Paris, K J; Spanos, W J; Lindberg, R D; Jose, B; Albrink, F

    1993-03-15

    To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

  1. Phase I biodistribution and pharmacokinetic study of Lewis Y targeting immunoconjugate CMD-193 in patients with advanced epithelial cancers

    International Nuclear Information System (INIS)

    Herbertson, R. A.; Lee, F. T.; Hopkins, W.; Smyth, F. E.; Murone, C.; Tebbutt, N. C.; Micallef, N.; MacFarlane, D. J.; Bellen, J.; Sonnichsen, D. S.; Brechbiel, M. W.; Scott, A. M.; Lee, T. L.

    2009-01-01

    Full text:Background: The Lewis Y (Ley) antigen is a blood-group related antigen expressed in >70% of solid tumours. This study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 (humanized anti-Ley antibody conjugated with calichaemicin) in patients with advanced Ley expressing epithelial cancers. Methods: There were 2 dose cohorts, (1.0mg/m2 and 2.6mg/m2). Primary objectives were to determine biodistribution and pharmacokinetics of CMD-193. The first cycle was labelled with 111In for biodistribution assessment, and subsequent cycles were administered 3 weekly to a maximum of 6 cycles. Tumour targeting was assessed using SPECT imaging, and pharmacokinetic analysis was based on gamma counting (111In-CMD-193) and ELISA (CMD-193 protein). Results: Nine patients were enrolled, and received 1-6 treatment cycles. Biodistribution imaging demonstrated initial blood pooling, followed by markedly increased hepatic uptake by day 2 (which persisted to day 8), and fast blood clearance. This pattern was seen for all patients, with no significant tumour uptake visualised in any patient. The overall T 1 /2 of 111In-CMD-193 complex formation in blood. One patient had partial metabolic response on 18F-FDG-PET. No radiologic responses were observed. Conclusions: CMD-193 demonstrates rapid blood clearance and increased hepatic uptake compared to prior studies of the original non-conjugated antibody. This trial highlights the importance of biodistribution and pharmacodynamic assessment in early phase studies of new biologics in clinical development.

  2. The significance of tumoral ERCC1 status in patients with locally advanced cervical cancer treated with chemoradiation therapy: a multicenter clinicopathologic analysis.

    Science.gov (United States)

    Doll, Corinne M; Aquino-Parsons, Christina; Pintilie, Melania; Klimowicz, Alexander C; Petrillo, Stephanie K; Milosevic, Michael; Craighead, Peter S; Clarke, Blaise; Lees-Miller, Susan P; Fyles, Anthony W; Magliocco, Anthony M

    2013-03-01

    ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis. Copyright © 2013. Published by Elsevier

  3. The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Doll, Corinne M., E-mail: Corinne.Doll@albertahealthservices.ca [Department of Oncology, University of Calgary, Calgary, AB (Canada); Aquino-Parsons, Christina [Department of Radiation Oncology, University of British Columbia, Vancouver, BC (Canada); Pintilie, Melania [Department of Biostatistics, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada); Klimowicz, Alexander C. [Department of Oncology, University of Calgary, Calgary, AB (Canada); Petrillo, Stephanie K. [Department of Pathology, University of Calgary, Calgary, AB (Canada); Milosevic, Michael [Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, ON (Canada); Craighead, Peter S. [Department of Oncology, University of Calgary, Calgary, AB (Canada); Clarke, Blaise [Department of Pathology, University of Toronto, Toronto, ON (Canada); Lees-Miller, Susan P. [Departments of Biochemistry and Molecular Biology, and Oncology, University of Calgary, Calgary, AB (Canada); Fyles, Anthony W. [Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, ON (Canada); Magliocco, Anthony M. [Department of Pathology, Lee Moffitt Cancer Center, Tampa, Florida (United States)

    2013-03-01

    Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on

  4. The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

    International Nuclear Information System (INIS)

    Doll, Corinne M.; Aquino-Parsons, Christina; Pintilie, Melania; Klimowicz, Alexander C.; Petrillo, Stephanie K.; Milosevic, Michael; Craighead, Peter S.; Clarke, Blaise; Lees-Miller, Susan P.; Fyles, Anthony W.; Magliocco, Anthony M.

    2013-01-01

    Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on

  5. Two-phase flow measurements with advanced instrumented spool pieces and local conductivity probes

    International Nuclear Information System (INIS)

    Turnage, K.G.; Davis, C.E.

    1979-01-01

    A series of two-phase, air-water and steam-water tests performed with instrumented spool pieces and with conductivity probes obtained from Atomic Energy of Canada, Ltd. is described. The behavior of the three-beam densitometer, turbine meter, and drag flowmeter is discussed in terms of two-phase models. Application of some two-phase mass flow models to the recorded spool piece data is made and preliminary results are shown. Velocity and void fraction information derived from the conductivity probes is presented and compared to velocities and void fractions obtained using the spool piece instrumentation

  6. Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer.

    Science.gov (United States)

    Shiomi-Mouri, Yukako; Kousaka, Junko; Ando, Takahito; Tetsuka, Rie; Nakano, Shogo; Yoshida, Miwa; Fujii, Kimihito; Akizuki, Miwa; Imai, Tsuneo; Fukutomi, Takashi; Kobayashi, Katsumasa

    2016-01-01

    Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3. We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios. With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p CEA and CA15-3.

  7. Composite advanced polymers for low moisture and oxygen permeability, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This Small Business Innovation Research Phase I program addresses NASA?s need for long duration shelf stable food by developing a high oxygen/moisture barrier...

  8. Advanced Nongray Radiation Module in the LOCI Framework for Combustion CFD, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Radiative heat fluxes are important in the design of launch vehicles for Project Constellation. In this Phase II STTR, CFDRC and its partner Mississippi State...

  9. Comparison of high-accuracy numerical simulations of black-hole binaries with stationary-phase post-Newtonian template waveforms for initial and advanced LIGO

    International Nuclear Information System (INIS)

    Boyle, Michael; Brown, Duncan A; Pekowsky, Larne

    2009-01-01

    We study the effectiveness of stationary-phase approximated post-Newtonian waveforms currently used by ground-based gravitational-wave detectors to search for the coalescence of binary black holes by comparing them to an accurate waveform obtained from numerical simulation of an equal-mass non-spinning binary black hole inspiral, merger and ringdown. We perform this study for the initial- and advanced-LIGO detectors. We find that overlaps between the templates and signal can be improved by integrating the match filter to higher frequencies than used currently. We propose simple analytic frequency cutoffs for both initial and advanced LIGO, which achieve nearly optimal matches, and can easily be extended to unequal-mass, spinning systems. We also find that templates that include terms in the phase evolution up to 3.5 post-Newtonian (pN) order are nearly always better, and rarely significantly worse, than 2.0 pN templates currently in use. For initial LIGO we recommend a strategy using templates that include a recently introduced pseudo-4.0 pN term in the low-mass (M ≤ 35 M o-dot ) region, and 3.5 pN templates allowing unphysical values of the symmetric reduced mass η above this. This strategy always achieves overlaps within 0.3% of the optimum, for the data used here. For advanced LIGO we recommend a strategy using 3.5 pN templates up to M = 12 M o-dot , 2.0 pN templates up to M = 21 M o-dot , pseudo-4.0 pN templates up to 65 M o-dot , and 3.5 pN templates with unphysical η for higher masses. This strategy always achieves overlaps within 0.7% of the optimum for advanced LIGO.

  10. Azacytidine in combination with tyrosine kinase inhibitors induced durable responses in patients with advanced phase chronic myelogenous leukemia.

    Science.gov (United States)

    Ruggiu, Mathilde; Oberkampf, Florence; Ghez, David; Cony-Makhoul, Pascale; Beckeriche, Florence; Cano, Isabelle; Taksin, Anne L; Benbrahim, Omar; Ghez, Stéphanie; Farhat, Hassan; Rigaudeau, Sophie; de Gunzburg, Noémie; Lara, Diane; Terre, Christine; Raggueneau, Victoria; Garcia, Isabel; Spentchian, Marc; De Botton, Stéphane; Rousselot, Philippe

    2017-11-28

    Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23.1 months. Hematologic response (HR) rate was 81.3%. Median overall survival (OS), event free survival and relapse-free survival (RFS) were 31.5, 23.3, and 32.2 months, respectively. All except one patient were treated as out-patients after the first cycle. Five patients were bridged to allogenic hematopoietic stem cells transplant. The combination of a TKI and azacytidine is a safe and efficient regiment for patients with CML patients in advanced phases.

  11. An advanced ultrasonic technique for slow and void fraction measurements of two-phase flow

    International Nuclear Information System (INIS)

    Faccini, J.L.H.; Su, J.; Harvel, G.D.; Chang, J.S.

    2004-01-01

    In this paper, we present a hybrid type counterpropagating transmission ultrasonic technique (CPTU) for flow and time averaging ultrasonic transmission intensity void fraction measurements (TATIU) of air-water two-phase flow, which is tested in the new two-phase flow test section mounted recently onto an existing single phase flow rig. The circular pipe test section is made of 51.2 mm stainless steel, followed by a transparent extruded acrylic pipe aimed at flow visualization. The two-phase flow rig operates in several flow regimes: bubbly, smooth stratified, wavy stratified and slug flow. The observed flow patterns are compared with previous experimental and numerical flow regime map for horizontal two phase flows. These flow patterns will be identified by time averaging transmission intensity ultrasonic techniques which have been developed to meet this particular application. A counterpropagating transmission ultrasonic flowmeter is used to measure the flow rate of liquid phase. A pulse-echo TATIU ultrasonic technique used to measure the void fraction of the horizontal test section is presented. We can draw the following conclusions: 1) the ultrasonic system was able to characterize the 2 flow patterns simulated (stratified and plug flow); 2) the results obtained for water volumetric fraction require more experimental work to determine exactly the technique uncertainties but, a priori, they are consistent with earlier work; and 3) the experimental uncertainties can be reduced by improving the data acquisition system, changing the acquisition time interval from seconds to milliseconds

  12. Textural features of pretreatment 18F-FDG PET/CT images: prognostic significance in patients with advanced T-stage oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Cheng, Nai-Ming; Fang, Yu-Hua Dean; Chang, Joseph Tung-Chieh; Huang, Chung-Guei; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Lin, Chien-Yu; Liao, Chun-Ta; Yen, Tzu-Chen

    2013-10-01

    Previous studies have shown that total lesion glycolysis (TLG) may serve as a prognostic indicator in oropharyngeal squamous cell carcinoma (OPSCC). We sought to investigate whether the textural features of pretreatment (18)F-FDG PET/CT images can provide any additional prognostic information over TLG and clinical staging in patients with advanced T-stage OPSCC. We retrospectively analyzed the pretreatment (18)F-FDG PET/CT images of 70 patients with advanced T-stage OPSCC who had completed concurrent chemoradiotherapy, bioradiotherapy, or radiotherapy with curative intent. All of the patients had data on human papillomavirus (HPV) infection and were followed up for at least 24 mo or until death. A standardized uptake value (SUV) of 2.5 was taken as a cutoff for tumor boundary. The textural features of pretreatment (18)F-FDG PET/CT images were extracted from histogram analysis (SUV variance and SUV entropy), normalized gray-level cooccurrence matrix (uniformity, entropy, dissimilarity, contrast, homogeneity, inverse different moment, and correlation), and neighborhood gray-tone difference matrix (coarseness, contrast, busyness, complexity, and strength). Receiver-operating-characteristic curves were used to identify the optimal cutoff values for the textural features and TLG. Thirteen patients were HPV-positive. Multivariate Cox regression analysis showed that age, tumor TLG, and uniformity were independently associated with progression-free survival (PFS) and disease-specific survival (DSS). TLG, uniformity, and HPV positivity were significantly associated with overall survival (OS). A prognostic scoring system based on TLG and uniformity was derived. Patients who presented with TLG > 121.9 g and uniformity ≤ 0.138 experienced significantly worse PFS, DSS, and OS rates than those without (P 121.9 g or uniformity ≤ 0.138 were further divided according to age, and different PFS and DSS were observed. Uniformity extracted from the normalized gray

  13. ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, E; Sørensen, J B

    2010-01-01

    Customized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participa...

  14. Treatment with docetaxel and cisplatin in advanced adrenocortical carcinoma, a phase II study

    DEFF Research Database (Denmark)

    Urup, Thomas; Pawlak, W Z; Petersen, P M

    2013-01-01

    Adrenocortical carcinoma (ACC) is a rare disease with a poor response to chemotherapy. Cisplatin is the most widely investigated drug in the treatment of ACC and in vitro studies have indicated activity of taxanes. The objectives of this study were to evaluate the efficacy and toxicity of cisplatin...... combined with docetaxel as first-line treatment of advanced ACC....

  15. Prognostic significance of catalase expression and its regulatory effects on hepatitis B virus X protein (HBx) in HBV-related advanced hepatocellular carcinomas.

    Science.gov (United States)

    Cho, Mi-Young; Cheong, Jae Youn; Lim, Wonchung; Jo, Sujin; Lee, Youngsoo; Wang, Hee-Jung; Han, Kyou-Hoon; Cho, Hyeseong

    2014-12-15

    Hepatitis B virus X protein (HBx) plays a role in liver cancer development. We previously showed that ROS increased HBx levels and here, we investigated the role of antioxidants in the regulation of HBx expression and their clinical relevance. We found that overexpression of catalase induced a significant loss in HBx levels. The cysteine null mutant of HBx (Cys-) showed a dramatic reduction in its protein stability. In clonogenic proliferation assays, Huh7-X cells produced a significant number of colonies whereas Huh7-Cys- cells failed to generate them. The Cys at position 69 of HBx was crucial to maintain its protein stability and transactivation function in response to ROS. Among 50 HBV-related hepatocellular carcinoma (HCC) specimens, 72% of HCCs showed lower catalase levels than those of surrounding non-tumor tissues. In advanced stage IV, catalase levels in non-tumor tissues were increased whereas those in tumors were further reduced. Accordingly, patients with a high T/N ratio for catalase showed significantly longer survival than those with a low T/N ratio. Together, catalase expression in HCC patients can be clinically useful for prediction of patient survival, and restoration of catalase expression in HCCs could be an important strategy for intervention in HBV-induced liver diseases.

  16. Prognostic significance of catalase expression and its regulatory effects on hepatitis B virus X protein (HBx) in HBV-related advanced hepatocellular carcinomas

    Science.gov (United States)

    Cho, Mi-Young; Cheong, Jae Youn; Lim, Wonchung; Jo, Sujin; Lee, Youngsoo; Wang, Hee-Jung; Han, Kyou-Hoon; Cho, Hyeseong

    2014-01-01

    Hepatitis B virus X protein (HBx) plays a role in liver cancer development. We previously showed that ROS increased HBx levels and here, we investigated the role of antioxidants in the regulation of HBx expression and their clinical relevance. We found that overexpression of catalase induced a significant loss in HBx levels. The cysteine null mutant of HBx (Cys−) showed a dramatic reduction in its protein stability. In clonogenic proliferation assays, Huh7-X cells produced a significant number of colonies whereas Huh7-Cys− cells failed to generate them. The Cys at position 69 of HBx was crucial to maintain its protein stability and transactivation function in response to ROS. Among 50 HBV-related hepatocellular carcinoma (HCC) specimens, 72% of HCCs showed lower catalase levels than those of surrounding non-tumor tissues. In advanced stage IV, catalase levels in non-tumor tissues were increased whereas those in tumors were further reduced. Accordingly, patients with a high T/N ratio for catalase showed significantly longer survival than those with a low T/N ratio. Together, catalase expression in HCC patients can be clinically useful for prediction of patient survival, and restoration of catalase expression in HCCs could be an important strategy for intervention in HBV-induced liver diseases. PMID:25361011

  17. Utility advanced turbine systems (ATS) technology readiness testing -- Phase 3. Annual report, October 1, 1996--September 30, 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The overall objective of the Advanced Turbine System (ATS) Phase 3 Cooperative Agreement between GE and the US Department of Energy (DOE) is the development of the GE 7H and 9H combined cycle power systems. The major effort will be expended on detail design. Validation of critical components and technologies will be performed including: hot gas path component testing, sub-scale compressor testing, steam purity test trials, and rotational heat transfer confirmation testing. Processes will be developed to support the manufacture of the first system. Technology enhancements that are not required for the first machine design but will be critical for future ATS advances in performance, reliability, and costs will be initiated. Long-term tests of materials to confirm design life predictions will continue. A schematic of the GE H machine is shown.

  18. Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas.

    Science.gov (United States)

    Müller, Mareike Hildegard; Rödel, Franz; Rüb, Udo; Korf, Horst-Werner

    2015-02-01

    The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells.

  19. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial.

    Science.gov (United States)

    Cheng, Ann-Lii; Kang, Yoon-Koo; Lin, Deng-Yn; Park, Joong-Won; Kudo, Masatoshi; Qin, Shukui; Chung, Hyun-Cheol; Song, Xiangqun; Xu, Jianming; Poggi, Guido; Omata, Masao; Pitman Lowenthal, Susan; Lanzalone, Silvana; Yang, Liqiang; Lechuga, Maria Jose; Raymond, Eric

    2013-11-10

    Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer. Patients were stratified and randomly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day. Primary end point was overall survival (OS). Early trial termination occurred for futility and safety reasons. A total of 1,074 patients were randomly assigned to the study (sunitinib arm, n = 530; sorafenib arm, n = 544). For sunitinib and sorafenib, respectively, median OS was 7.9 versus 10.2 months (hazard ratio [HR], 1.30; one-sided P = .9990; two-sided P = .0014); median progression-free survival (PFS; 3.6 v 3.0 months; HR, 1.13; one-sided P = .8785; two-sided P = .2286) and time to progression (TTP; 4.1 v 3.8 months; HR, 1.13; one-sided P = .8312; two-sided P = .3082) were comparable. Median OS was similar among Asian (7.7 v 8.8 months; HR, 1.21; one-sided P = .9829) and hepatitis B-infected patients (7.6 v 8.0 months; HR, 1.10; one-sided P = .8286), but was shorter with sunitinib in hepatitis C-infected patients (9.2 v 17.6 months; HR, 1.52; one-sided P = .9835). Sunitinib was associated with more frequent and severe adverse events (AEs) than sorafenib. Common grade 3/4 AEs were thrombocytopenia (29.7%) and neutropenia (25.7%) for sunitinib; hand-foot syndrome (21.2%) for sorafenib. Discontinuations owing to AEs were similar (sunitinib, 13.3%; sorafenib, 12.7%). OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib. OS was comparable in Asian and hepatitis B-infected patients. OS was superior in hepatitis C-infected patients who received sorafenib. Sunitinib-treated patients reported more frequent and severe toxicity.

  20. Results from a Phase I Study of Lapatinib with Gemcitabine and Cisplatin in Advanced or Metastatic Bladder Cancer

    DEFF Research Database (Denmark)

    Cerbone, L; Sternberg, C N; Sengeløv, L

    2016-01-01

    BACKGROUND/OBJECTIVE: Lapatinib is a potent HER1 and HER2 inhibitor. Gemcitabine-cisplatin (GC) is a standard chemotherapy regimen for advanced/metastatic bladder cancer. This phase I study examined the safety of lapatinib in combination with GC in patients with bladder cancer. The primary aim...... × 3 patients), 1 of the 6 patients presented DLTs (grade 4, treatment-related febrile neutropenia and renal failure). Twelve patients received 6 cycles. CONCLUSIONS: Lapatinib at 750-1,250 mg combined with GC appears safe and tolerable. The MTD of lapatinib combined with GC in bladder cancer was 1...

  1. AISI/DOE Advanced Process Control Program Vol. 5 of 6: Phase Measurement of Galvanneal

    Energy Technology Data Exchange (ETDEWEB)

    Cristopher Burnett; Ronald Guel; James R. Philips; L. Lowry; Beverly Tai

    1999-05-31

    Augmentation of the internal software of a commercial X-ray fluorescence gauge is shown to enable the instrument to extend its continuous on-line real-time measurements of a galvanneal coating's total elemental content to encompass similar measurements of the relative thickness of the coating's three principal metallurgical phases. The mathematical structure of this software augmentation is derived from the theory of neural networks. The performance of the augmented gauge is validated by comparing the gauge implied real-time phase distribution with the phase distribution independently measured off-line on between the gauge and laboratory measurements and to suggest preferred approaches to be followed in future application of the augmented gauge.

  2. A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

    Science.gov (United States)

    Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

    2016-08-17

    This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

  3. Advanced supersonic propulsion study, phases 3 and 4. [variable cycle engines

    Science.gov (United States)

    Allan, R. D.; Joy, W.

    1977-01-01

    An evaluation of various advanced propulsion concepts for supersonic cruise aircraft resulted in the identification of the double-bypass variable cycle engine as the most promising concept. This engine design utilizes special variable geometry components and an annular exhaust nozzle to provide high take-off thrust and low jet noise. The engine also provides good performance at both supersonic cruise and subsonic cruise. Emission characteristics are excellent. The advanced technology double-bypass variable cycle engine offers an improvement in aircraft range performance relative to earlier supersonic jet engine designs and yet at a lower level of engine noise. Research and technology programs required in certain design areas for this engine concept to realize its potential benefits include refined parametric analysis of selected variable cycle engines, screening of additional unconventional concepts, and engine preliminary design studies. Required critical technology programs are summarized.

  4. Study Protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease

    Directory of Open Access Journals (Sweden)

    Brafman-Kennedy Barbara

    2011-05-01

    Full Text Available Abstract Background Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS seeks to improve the care of breathless patients with advanced disease (regardless of cause through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed. This paper presents the protocol for Phase III. Methods/Design Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks and one for patients with non-malignant disease (intervention delivered over four weeks. The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol and one for patients with non-malignant conditions (eight week protocol. Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only. The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10. The trial includes economic evaluation. Analysis will be on an intention to treat basis. Discussion This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast

  5. DE-FOA-EE0005502 Advanced Percussive Drilling Technology for Geothermal Exploration and Development Phase II Report.

    Energy Technology Data Exchange (ETDEWEB)

    Su, Jiann-Cherng [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Raymond, David W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Prasad, Somuri V. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolfer, Dale R. [Atlas-Copco Secoroc, LLC, Fagersta (Sweden)

    2017-05-01

    Percussive hammers are a promising advance in drilling technology for geothermal since they rely upon rock reduction mechanisms that are well-suited for use in the hard, brittle rock characteristic of geothermal formations. The project research approach and work plan includes a critical path to development of a high-temperature (HT) percussive hammer using a two- phase approach. The work completed in Phase I of the project demonstrated the viability of percussive hammers and that solutions to technical challenges in design, material technology, and performance are likely to be resolved. Work completed in Phase II focused on testing the findings from Phase I and evaluating performance of the materials and designs at high- operating temperatures. A high-operating temperature (HOT) drilling facility was designed, built, and used to test the performance of the DTH under extreme conditions. Results from the testing indicate that a high-temperature capable hammer can be developed and is a viable alternative for user in the driller's toolbox.

  6. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study

    Energy Technology Data Exchange (ETDEWEB)

    Trip, Anouk K. [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Poppema, Boelo J. [Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Berge Henegouwen, Mark I. van [Department of Surgical Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Siemerink, Ester [Department of Internal Medicine, Ziekenhuisgroep Twente, Hengelo (Netherlands); Beukema, Jannet C. [Department of Radiation Oncology, University Medical Centre Groningen (Netherlands); Verheij, Marcel [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Plukker, John T.M. [Department of Surgical Oncology, University Medical Centre Groningen (Netherlands); Richel, Dick J. [Department of Medical Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Hulshof, Maarten C.C.M. [Department of Radiation Oncology, Academic Medical Centre – University of Amsterdam (Netherlands); Sandick, Johanna W. van [Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Cats, Annemieke [Department of Gastroenterology and Hepatology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Jansen, Edwin P.M. [Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Hospers, Geke A.P., E-mail: g.a.p.hospers@umcg.nl [Department of Medical Oncology, University Medical Centre Groningen (Netherlands)

    2014-08-15

    Objectives: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods: In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results: Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions: In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates.

  7. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study

    International Nuclear Information System (INIS)

    Trip, Anouk K.; Poppema, Boelo J.; Berge Henegouwen, Mark I. van; Siemerink, Ester; Beukema, Jannet C.; Verheij, Marcel; Plukker, John T.M.; Richel, Dick J.; Hulshof, Maarten C.C.M.; Sandick, Johanna W. van; Cats, Annemieke; Jansen, Edwin P.M.; Hospers, Geke A.P.

    2014-01-01

    Objectives: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods: In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results: Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions: In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates

  8. Advanced Concept Studies for Supersonic Commercial Transports Entering Service in the 2018-2020 Period Phase 2

    Science.gov (United States)

    Morgenstern, John; Buonanno, Michael; Yao, Jixian; Murugappan, Mugam; Paliath, Umesh; Cheung, Lawrence; Malcevic, Ivan; Ramakrishnan, Kishore; Pastouchenko, Nikolai; Wood, Trevor; hide

    2015-01-01

    Lockheed Martin Aeronautics Company (LM), working in conjunction with General Electric Global Research (GE GR) and Stanford University, executed a 19 month program responsive to the NASA sponsored "N+2 Supersonic Validation: Advanced Concept Studies for Supersonic Commercial Transports Entering Service in the 2018-2020 Period" contract. The key technical objective of this effort was to validate integrated airframe and propulsion technologies and design methodologies necessary to realize a supersonic vehicle capable of meeting the N+2 environmental and performance goals. The N+2 program is aligned with NASA's Supersonic Project and is focused on providing system level solutions capable of overcoming the efficiency, environmental, and performance barriers to practical supersonic flight. The N+2 environmental and performance goals are outlined in the technical paper, AIAA-2014-2138 (Ref. 1) along with the validated N+2 Phase 2 results. Our Phase 2 efforts built upon our Phase 1 studies (Ref. 2) and successfully demonstrated the ability to design and test realistic configurations capable of shaped sonic booms over the width of the sonic boom carpet. Developing a shaped boom configuration capable of meeting the N+2 shaped boom targets is a key goal for the N+2 program. During the LM Phase 1 effort, LM successfully designed and tested a shaped boom trijet configuration (1021) capable of achieving 85 PLdB under track (forward and aft shock) and up to 28 deg off-track at Mach 1.6. In Phase 2 we developed a refined configuration (1044-2) that extended the under 85 PLdB sonic boom level over the entire carpet of 52 deg off-track at a cruise Mach number of 1.7. Further, the loudness level of the configuration throughout operational conditions calculates to an average of 79 PLdB. These calculations rely on propagation employing Burger's (sBOOM) rounding methodology, and there are indications that the configuration average loudness would actually be 75 PLdB. We also added

  9. Advanced Coating Technology for Enhanced Performance of Microchannel Plates for UV Detectors, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — In this NASA SBIR Phase I proposal we propose to apply a highly conformal coating of ZnO and AlN or a double layer of GaN to the surface and internal pore walls of...

  10. Recent Advances in Atmospheric Vapor-Phase Deposition of Transparent and Conductive Zinc Oxide

    NARCIS (Netherlands)

    Illiberi, A.; Poodt, P.; Roozeboom, F.

    2014-01-01

    The industrial need for high-throughput and low-cost ZnO deposition processes has triggered the development of atmospheric vapor-phase deposition techniques which can be easily applied to continuous, in-line manufacturing. While atmospheric CVD is a mature technology, new processes for the growth of

  11. COUPLING STATE-OF-THE-SCIENCE SUBSURFACE SIMULATION WITH ADVANCED USER INTERFACE AND PARALLEL VISUALIZATION: SBIR Phase I Final Report

    International Nuclear Information System (INIS)

    Hardeman, B.; Swenson, D.; Finsterle, S.; Zhou, Q.

    2008-01-01

    This is a Phase I report on a project to significantly enhance existing subsurface simulation software using leadership-class computing resources, allowing researchers to solve problems with greater speed and accuracy. Subsurface computer simulation is used for monitoring the behavior of contaminants around nuclear waste disposal and storage areas, groundwater flow, environmental remediation, carbon sequestration, methane hydrate production, and geothermal energy reservoir analysis. The Phase I project was a collaborative effort between Thunderhead Engineering (project lead and developers of a commercial pre- and post-processor for the TOUGH2 simulator) and Lawrence Berkeley National Laboratory (developers of the TOUGH2 simulator for subsurface flow). The Phase I project successfully identified the technical approaches to be implemented in Phase II.

  12. Significance of lymphadenectomy with splenectomy in radical surgery for advanced (pT3/pT4) remnant gastric cancer.

    Science.gov (United States)

    Sugita, Hiroki; Oda, Eri; Hirota, Masahiko; Ishikawa, Shinji; Tomiyasu, Shinjiro; Tanaka, Hiroshi; Arita, Tetsumasa; Yagi, Yasushi; Baba, Hideo

    2016-04-01

    To date, the optimal surgical strategy for remnant gastric cancer has not been determined. The purpose of this study was to clarify the significance of lymphadenectomy with splenectomy in remnant gastric cancer surgery. This retrospective cohort study was conducted at the Kumamoto Regional Medical Center. The primary endpoint was overall survival after surgery. We retrospectively analyzed the clinicopathologic features, surgical treatments, and long-term prognosis of remnant gastric cancer patients treated with total gastrectomy. A total of 80 patients with gastric cancer in the remnant stomach after distal gastrectomy and who underwent total gastrectomy were enrolled in the study. Splenectomy was performed in 38 patients. Lymph node metastasis in the splenic hilum was not observed in the patients with pT1/pT2 tumors, whereas nodal metastasis at the splenic hilum was detected in 30.4% of the patients with pT3/pT4 tumors. The survival rate of the patients with pT3/pT4 tumors who underwent splenectomy was significantly higher than that of the patients who did not undergo splenectomy, although there was no difference in the patients with pT1/pT2 tumors. Among the patients classified as R0, the survival rate of the patients with pT3/pT4 tumors who underwent splenectomy was significantly higher than that of the patients who did not undergo splenectomy. Lymphadenectomy with splenectomy in radical surgery is beneficial for patients with advanced (pT3/pT4) remnant gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI in Patients with Small Cell Lung Cancer_ Comparison with Original ALI.

    Directory of Open Access Journals (Sweden)

    Eun Young Kim

    Full Text Available Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR] has been shown to predict overall survival (OS in small cell lung cancer (SCLC. CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI using CT-determined L3 muscle index (L3MI, muscle area at L3/height2 beyond original ALI.L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable.Patients with low ALI (cut-off, 31.1, n = 94 had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001, and patients with low mALI (cut-off 67.7, n = 94 had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001. There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000 and between high ALI and high mALI (z = 0.330, p = 0.740. Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004, along with advanced age (HR, 1.49, p = 0.045, extensive disease (HR, 2.27, p < 0.001, supportive care only (HR, 7.86, p < 0.001, and elevated LDH (HR, 1.45, p = 0.037. Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136.The present study confirms mALI using CT-determined L3MI has no additional prognostic value beyond original ALI using BMI. ALI

  14. Advanced high speed X-ray CT scanner for measurement and visualization of multi-phase flow

    International Nuclear Information System (INIS)

    Hori, Keiichi; Fujimoto, Tetsuro; Kawanishi, Kohei; Nishikawa, Hideo

    1998-01-01

    The development of an ultra-fast X-ray computed tomography (CT) scanner has been performed. The object of interest is in a transient or unsettled state, which makes the conventional CT scanner inappropriate. A concept of electrical switching of electron beam of X-ray generation unit is adopted to reduce the scanning time instead of a mechanical motion adopted by a conventional CT scanner. The mechanical motion is a major obstacle to improve the scanning speed. A prototype system with a scanning time of 3.6 milliseconds was developed at first. And, the feasibility was confirmed to measure the dynamic events of two-phase flow. However, faster scanning speed is generally required for the practical use in the thermalhydraulics research field. Therefore, the development of advanced type has been performed. This advanced type can operate under the scanning time of 0.5 milliseconds and is applicable for the measurement of the multi-phase flow with velocity up to 4-5 m/s. (author)

  15. The long-term effects of phase advance shifts of photoperiod on cardiovascular parameters as measured by radiotelemetry in rats

    International Nuclear Information System (INIS)

    Molcan, L; Vesela, A; Zeman, M; Teplan, M

    2013-01-01

    Cardiovascular parameters, such as blood pressure and heart rate, exhibit both circadian and ultradian rhythms which are important for the adequate functioning of the system. For a better understanding of possible negative effects of chronodisruption on the cardiovascular system we studied circadian and ultradian rhythms of blood pressure and heart rate in rats exposed to repeated 8 h phase advance shifts of photoperiod. The experiment lasted 12 weeks, with three shifts per week. Spectral power as a function of frequency for both circadian and harmonic ultradian rhythms was expressed as the circadian–ultradian power ratio. The circadian rhythms of blood pressure, heart rate and locomotor activity were recorded during the control light:dark (LD) regimen with higher values during the D in comparison with the L. Phase advance shifts resulted in a diminished circadian–ultradian power ratio for blood pressure, heart rate and locomotor activity indicating suppressed circadian control of these traits greater in heart rate than blood pressure. In conclusion, rats kept under irregular LD conditions have suppressed circadian control of heart rate, blood pressure and locomotor activity and rely more on an acute response to the LD regime. Their ability to anticipate regular loads can be weakened and in this way chronodisruption can contribute to the pathogenesis of cardiovascular diseases. (paper)

  16. Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: Acute toxicity results of a phase I study

    International Nuclear Information System (INIS)

    Urbano, Teresa Guerrero; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; Miles, Elizabeth A.; Mc Nair, Helen; Bidmead, A. Margaret; Warrington, Jim; Dearnaley, David P.; Harmer, Clive; Harrington, Kevin J.; Nutting, Christopher M.

    2007-01-01

    Background and purpose: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. Methods: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. Results: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G ≤ 1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. Conclusions: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects

  17. Study of Second Phase Particles and Fe content in Zr Alloys Using the Advanced Photon Source at Argonne

    Energy Technology Data Exchange (ETDEWEB)

    Arthur T. Motta

    2001-11-07

    We have conducted a study of second phase particles and matrix alloying element concentrations in zirconium alloys using synchrotron radiation from the Advanced Photon Source (APS) at Argonne National Laboratory. The high flux of synchrotron radiation delivered at the 2BM beamline compared to conventional x-ray generators, enables the detection of very small precipitate volume fractions. We detected the standard C14 hcp Zr(Cr,Fe)2 precipitates, (the stable second phase in Zircaloy-4) in the bulk material at a cumulative annealing parameter as low as 10-20 h, and we followed the kinetics of precipitation and growth as a function of the cumulative annealing parameter (CAP) in the range 10-22 (quench) to 10-16 h. In addition, the unique combination of spatial resolution and elemental sensitivity of the 2ID-D/E microbeam line at the Advanced Photon Source at Argonne (APS) allows study of the alloying element concentrations at ppm levels in an area as small as 0.2 mm. We used x-ray fluorescence induced by this sub-micron x-ray beam to determine the concentration of these alloying elements in the matrix as a function of alloy type and thermal history. We discuss these results and the potential of synchrotron radiation-based techniques for studying zirconium alloys.

  18. Study of Second Phase Particles and Fe content in Zr Alloys Using the Advanced Photon Source at Argonne

    International Nuclear Information System (INIS)

    Motta, Arthur T.

    2001-01-01

    We have conducted a study of second phase particles and matrix alloying element concentrations in zirconium alloys using synchrotron radiation from the Advanced Photon Source (APS) at Argonne National Laboratory. The high flux of synchrotron radiation delivered at the 2BM beamline compared to conventional x-ray generators, enables the detection of very small precipitate volume fractions. We detected the standard C14 hcp Zr(Cr,Fe)2 precipitates, (the stable second phase in Zircaloy-4) in the bulk material at a cumulative annealing parameter as low as 10-20 h, and we followed the kinetics of precipitation and growth as a function of the cumulative annealing parameter (CAP) in the range 10-22 (quench) to 10-16 h. In addition, the unique combination of spatial resolution and elemental sensitivity of the 2ID-D/E microbeam line at the Advanced Photon Source at Argonne (APS) allows study of the alloying element concentrations at ppm levels in an area as small as 0.2 mm. We used x-ray fluorescence induced by this sub-micron x-ray beam to determine the concentration of these alloying elements in the matrix as a function of alloy type and thermal history. We discuss these results and the potential of synchrotron radiation-based techniques for studying zirconium alloys

  19. Advanced Turbine Systems (ATS). Phase 1: System scoping and feasibility studies

    Science.gov (United States)

    White, D. J.

    1993-04-01

    As part of this involvement, Solar intends to design and commercialize a unique gas turbine system that promises high cycle efficiencies and low exhaust emissions. This engine of approximately 12-MW will be targeted for the dispersed power markets both urban and rural. Goals of 50% thermal efficiency and 8 parts-per-million by volume (ppmv) nitrogen oxide emissions were established. Reliability, availability, and maintainability (RAM) will continue to be the most important factors in the competitive marketplace. The other major goal adopted was one of reducing the cost of power produced by 10%. This reduction is based on the cost of power (COP) associated with today's engines that lie in the same horsepower range as that targeted in this study. An advanced cycle based on an approximation of the Ericsson Cycle was adopted after careful studies of a number of different cycles. This advanced intercooled, recuperated engine when fired at 2450 F will be capable of meeting the 50% efficiency goal if the cooling air requirements do not exceed 7% of the total air flow rate. This latter qualification will probably dictate the use of ceramic parts for both the nozzle guide vanes and the turbine blades. Cooling of these parts will probably be required and the 7% cooling flow allowance is thought to be adequate for such materials. Analyses of the cost of power and RAM goals show that the installed cost of this advanced engine can be approximately 50% above today's costs. This cost is based on $4.00 per million Btu fuel and a COP reduction of 10% while maintaining the same RAM as today's engines.

  20. Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study

    Science.gov (United States)

    GADALETA-CALDAROLA, GENNARO; INFUSINO, STEFANIA; GALISE, IDA; RANIERI, GIROLAMO; VINCIARELLI, GIANLUCA; FAZIO, VITO; DIVELLA, ROSA; DANIELE, ANTONELLA; FILIPPELLI, GIANFRANCO; GADALETA, COSMO DAMIANO

    2014-01-01

    The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55–73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2–6.2) and 10.4 (95% CI, 10–11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC. PMID:25202410

  1. Nanoencapsulation of phase change materials for advanced thermal energy storage systems

    Science.gov (United States)

    Shchukina, E. M.; Graham, M.; Zheng, Z.

    2018-01-01

    Phase change materials (PCMs) allow the storage of large amounts of latent heat during phase transition. They have the potential to both increase the efficiency of renewable energies such as solar power through storage of excess energy, which can be used at times of peak demand; and to reduce overall energy demand through passive thermal regulation. 198.3 million tons of oil equivalent were used in the EU in 2013 for heating. However, bulk PCMs are not suitable for use without prior encapsulation. Encapsulation in a shell material provides benefits such as protection of the PCM from the external environment and increased specific surface area to improve heat transfer. This review highlights techniques for the encapsulation of both organic and inorganic PCMs, paying particular attention to nanoencapsulation (capsules with sizes energy release/uptake. PMID:29658558

  2. Nanoencapsulation of phase change materials for advanced thermal energy storage systems.

    Science.gov (United States)

    Shchukina, E M; Graham, M; Zheng, Z; Shchukin, D G

    2018-04-16

    Phase change materials (PCMs) allow the storage of large amounts of latent heat during phase transition. They have the potential to both increase the efficiency of renewable energies such as solar power through storage of excess energy, which can be used at times of peak demand; and to reduce overall energy demand through passive thermal regulation. 198.3 million tons of oil equivalent were used in the EU in 2013 for heating. However, bulk PCMs are not suitable for use without prior encapsulation. Encapsulation in a shell material provides benefits such as protection of the PCM from the external environment and increased specific surface area to improve heat transfer. This review highlights techniques for the encapsulation of both organic and inorganic PCMs, paying particular attention to nanoencapsulation (capsules with sizes energy release/uptake.

  3. Phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus. Nine Japanese institutions trial

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Kaoru [Iwate Medical Univ., Morioka (Japan). School of Medicine; Iizuka, Toshifumi; Ando, Nobutoshi; Ide, Hiroko

    1996-10-01

    A phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus was carried out cooperatively by nine Japanese institutions. Forty-five patients with thoracic advanced squamous cell carcinoma, who had T4 tumor or distant lymph node metastasis (M1{sub (LYM)}), were enrolled in the study for treatment with cisplatin (70 mg/m{sup 2}) on days 1 and 36, and 5-fluorouracil infusion (700 mg/m{sup 2}) on days 1-4 and 36-39 sandwiched around external beam irradiation (60 Gy over 6 weeks). Of the 45 evaluable patients, 37 (84.1%) completed the treatment. The overall response rate was 64.4%, and the complete response rate 8.9%. The median duration of response was 125.0 days for patients who achieved complete and partial response. The 50% median survival time was 215 days. There was one toxicity-related death due to radiation pneumonitis. The major form of toxicity exceeding grade 2 was myelosuppression and anorexia, but grade 4 toxicity was also observed (2 pulmonary, 1 severe hypoxemia, 1 severe cardiac failure and 1 mental disturbance). The results showed that this form of chemoradiotherapy had a satisfactory effect and might be useful for treatment of inoperable advanced esophageal cancer. (author)

  4. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study

    Science.gov (United States)

    Strumberg, D; Scheulen, M E; Schultheis, B; Richly, H; Frost, A; Büchert, M; Christensen, O; Jeffers, M; Heinig, R; Boix, O; Mross, K

    2012-01-01

    Background: In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC). Methods: Patients received oral regorafenib 60–220 mg daily (160 mg daily in the extension cohort) in cycles of 21 days on, 7 days off treatment. Assessments included toxicity, response, pharmacokinetics and pharmacodynamics. Results: Thirty-eight patients with heavily pretreated CRC (median 4 prior lines of therapy, range 0–7) were enrolled in the dose-escalation and extension phases; 26 patients received regorafenib 160 mg daily. Median treatment duration was 53 days (range 7–280 days). The most common treatment-related toxicities included hand–foot skin reaction, fatigue, voice change and rash. Twenty-seven patients were evaluable for response: 1 achieved partial response and 19 had stable disease. Median progression-free survival was 107 days (95% CI, 66–161). At steady state, regorafenib and its active metabolites had similar systemic exposure. Pharmacodynamic assessment indicated decreased tumour perfusion in most patients. Conclusion: Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC. This expanded-cohort phase I study provided the foundation for further clinical trials of regorafenib in this patient population. PMID:22568966

  5. Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials.

    Directory of Open Access Journals (Sweden)

    Ping Fang

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. METHODS: PubMed, the Cochrane Library, and Google Scholar were searched using the terms "bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable". Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS, tumor response, and toxicities. RESULTS: A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial or in combination with erlotinib (n = 4 trials, capecitabine (n = 1 trial, capecitabine+oxaliplatin (n = 1 trial, or gemcitabine+oxaliplatin (n = 1 trial. Most trials (five of eight reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%, fatigue (12%, hypertension (10%, diarrhea (8%, and neutropenia (5%. Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12, typically due to esophageal varices. CONCLUSIONS: Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently

  6. Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations

    NARCIS (Netherlands)

    Zimmer, Lisa; Barlesi, Fabrice; Martinez-Garcia, Maria; Dieras, Veronique; Schellens, Jan H M; Spano, Jean-Philippe; Middleton, Mark R; Calvo, Emiliano; Paz-Ares, Luiz; Larkin, James; Pacey, Simon; Venturi, Miro; Kraeber-Bodéré, Françoise; Tessier, Jean J L; Eberhardt, Wilfried Ernst Erich; Paques, Michel; Guarin, Ernesto; Meresse, Valerie; Soria, Jean-Charles

    2014-01-01

    PURPOSE: This phase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor. EXPERIMENTAL DESIGN: We undertook a multicenter phase I two-part study (dose escalation and cohort expansion).

  7. Imatinib mesylate is effective in children with chronic myelogenous leukemia in late chronic and advanced phase and in relapse after stem cell transplantation

    NARCIS (Netherlands)

    Millot, F; Guilhot, J; Nelken, B; Leblanc, T; De Bont, ES; Bekassy, AN; Gadner, H; Sufliarska, S; Stary, J; Gschaidmeier, H; Guilhot, F; Suttorp, M

    A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon a-based regimen. In

  8. A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Gustav J Ullenhag

    Full Text Available Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15, each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily. The maximum tolerated dose (MTD of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25% subjects experiences a dose-limiting toxicity (DLT. Patients should also be able to receive daily low molecular weight heparin (LMWH (e.g. dalteparin 5000 IU s.c. daily as a prophylactic anticoagulant for venous thromboembolic events (VTEs. Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively were enrolled in this study.Median duration of treatment was 11 weeks (range 1-66, and median number of treatment cycles were three (range 1-14. The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs (all grades included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia; thrombocytopenia (75%; dermatological toxicity (75%; diarrhea and nausea (42% each; and neuropathy (42%.This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.ClinicalTrials.gov NCT

  9. A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer.

    Science.gov (United States)

    Cohen, Steven J; Zalupski, Mark M; Modiano, Manuel R; Conkling, Paul; Patt, Yehuda Z; Davis, Peg; Dorr, Robert T; Boytim, Michelle L; Hersh, Evan M

    2010-07-01

    Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2) IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min on days 1, 8, and 15 every 28 days). One hundred five patients received 340 treatment cycles (median 2, range 1-16). median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. The recommended phase II dose of imexon is 875 mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.

  10. A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

    International Nuclear Information System (INIS)

    Chitapanarux, Imjai; Chomprasert, Kittisak; Nobnaop, Wannapa; Wanwilairat, Somsak; Tharavichitkul, Ekasit; Jakrabhandu, Somvilai; Onchan, Wimrak; Patrinee, Traisathit; Gestel, Dirk Van

    2015-01-01

    The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose-volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm 3 (30.5%) and 5.4 cm 3 (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6-5.9 Gy, P < 0.001 and 2.1-9.9 Gy, P < 0.001, respectively). The D mean of the contralateral parotid decreased in 70% of the patients (range, 0.2-4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC. (author)

  11. Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

    Science.gov (United States)

    Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

    2011-06-01

    First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

  12. A phase Ib study of everolimus combined with metformin for patients with advanced cancer.

    Science.gov (United States)

    Molenaar, Remco J; van de Venne, Tim; Weterman, Mariëtte J; Mathot, Ron A; Klümpen, Heinz-Josef; Richel, Dick J; Wilmink, Johanna W

    2018-02-01

    Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4-78). 6 patients discontinued due to toxicity and 3 patients because of progressive disease. At the starting dose level of 10 mg everolimus qd and 500 mg metformin bid, 3 out of 5 patients experienced a DLT. After de-escalation to 5 mg everolimus qd and 500 mg metformin bid, considerable toxicity was still observed and patient enrollment was terminated. In pharmacokinetic analyses, metformin was eliminated slower when co-administered with everolimus than as single-agent. After 9 weeks of treatment, 3 patients were still on study and all had stable disease. Conclusion The combination of everolimus and metformin is poorly tolerated in patients with advanced cancer. The pharmacokinetic interaction between everolimus and metformin may have implications for diabetic cancer patients that are treated with these drugs. Our results advocate for future clinical trials with combinations of other mTOR inhibitors and biguanides.

  13. Prevalence and clinical significance of cancer cachexia based on time from treatment in advanced-stage head and neck squamous cell carcinoma.

    Science.gov (United States)

    Kwon, Minsu; Kim, Rock Bum; Roh, Jong-Lyel; Lee, Sang-Wook; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

    2017-04-01

    The purpose of this study was to identify the prevalence of cancer cachexia and its prognostic impact in patients with advanced head and neck squamous cell carcinoma (HNSCC). The prevalence of cancer cachexia was analyzed according to the follow-up periods during the first year after curative initial treatment. Recurrences, noncancer health events (NCHEs), and cause-specific survival outcomes were also analyzed according to the incidence of cancer cachexia during follow-up. Cancer cachexia was identified in 22 (6.1%), 148 (41%), 66 (18.4%), and 65 (18.7%) of 361 enrolled patients at pretreatment, immediately after treatment, 6-months after treatment, and 12-months after treatment, respectively. Sustained or newly developed cachexia at 6 and 12 months showed a significant association with recurrence and NCHE occurrence (p cachexia had a higher probability of cancer-specific death, noncancerous death, and overall death (p Cachexia prevalence at 6 and 12 months after treatment for HNSCC indicates a higher chance of recurrence, NCHE, and death. © 2016 Wiley Periodicals, Inc. Head Neck 39: 716-723, 2017. © 2016 Wiley Periodicals, Inc.

  14. Optical Measurement Technologies for High Temperature, Radiation Exposure, and Corrosive Environments—Significant Activities and Findings: In-vessel Optical Measurements for Advanced SMRs

    Energy Technology Data Exchange (ETDEWEB)

    Anheier, Norman C.; Cannon, Bret D.; Qiao, Hong (Amy); Suter, Jonathan D.

    2012-09-01

    Development of advanced Small Modular Reactors (aSMRs) is key to providing the United States with a sustainable, economically viable, and carbon-neutral energy source. The aSMR designs have attractive economic factors that should compensate for the economies of scale that have driven development of large commercial nuclear power plants to date. For example, aSMRs can be manufactured at reduced capital costs in a factory and potentially shorter lead times and then be shipped to a site to provide power away from large grid systems. The integral, self-contained nature of aSMR designs is fundamentally different than conventional reactor designs. Future aSMR deployment will require new instrumentation and control (I&C) architectures to accommodate the integral design and withstand the extreme in-vessel environmental conditions. Operators will depend on sophisticated sensing and machine vision technologies that provide efficient human-machine interface for in-vessel telepresence, telerobotic control, and remote process operations. The future viability of aSMRs is dependent on understanding and overcoming the significant technical challenges involving in-vessel reactor sensing and monitoring under extreme temperatures, pressures, corrosive environments, and radiation fluxes

  15. Intensity-Modulated Whole Abdominal Radiotherapy After Surgery and Carboplatin/Taxane Chemotherapy for Advanced Ovarian Cancer: Phase I Study

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D.; Dinkel, Julien; Herfarth, Klaus K.; Schubert, Kai; Eichbaum, Michael H.; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2010-01-01

    Purpose: To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Methods and Materials: Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Results: Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. Conclusions: The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

  16. Intensity-modulated whole abdominal radiotherapy after surgery and carboplatin/taxane chemotherapy for advanced ovarian cancer: phase I study.

    Science.gov (United States)

    Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D; Dinkel, Julien; Herfarth, Klaus K; Schubert, Kai; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2010-04-01

    To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

  17. Phase I and pharmacodynamic study of vorinostat combined with capecitabine and cisplatin as first-line chemotherapy in advanced gastric cancer.

    Science.gov (United States)

    Yoo, Changhoon; Ryu, Min-Hee; Na, Young-Soon; Ryoo, Baek-Yeol; Lee, Chae-Won; Maeng, Jeheon; Kim, Se-Yeon; Koo, Dong Hoe; Park, Inkeun; Kang, Yoon-Koo

    2014-04-01

    A phase I trial of first-line vorinostat, an orally bio-available histone deacetylase inhibitor, in combination with capecitabine plus cisplatin (XP) was performed to assess recommend phase II trial dose in patients with advanced gastric cancer. Five dose levels of three-weekly vorinostat-XP were tested; vorinostat was dosed at 300-400 mg once daily on Days 1-14, capecitabine at 800-1,000 mg/m(2) twice daily on Days 1-14, and cisplatin at 60-80 mg/m(2) on Day 1. To assess the pharmacodynamics of vorinostat, histone H3 acetylation was assessed in peripheral blood mononuclear cells before the study treatment and at Day 8 of cycle 1. In total, 30 patients with unresectable or metastatic gastric adenocarcinoma were included. Dose-limiting toxicities were thrombocytopenia, fatigue, stomatitis, and anorexia. The following doses were recommended for phase II trial: 400 mg of vorinostat once daily, 1,000 mg/m(2) of capecitabine twice daily, and 60 mg/m(2) of cisplatin. The most common grade 3-4 toxicities were neutropenia (47 %), anorexia (20 %), thrombocytopenia (17 %), and fatigue (13 %). In overall, response rate was 56 % (95 % confidence interval [CI]: 32-81). With a median follow-up of 14.1 months, the median progression-free survival and overall survival were 7.1 months (95 % CI: 3.8-10.3) and 18.0 months (95 % CI: 4.8-31.1), respectively. The change in H3 acetylation after treatment with vorinostat correlated significantly with the vorinostat dose (300 vs. 400 mg/day) and the baseline level of H3 acetylation before treatment. Three-weekly vorinostat-XP regimen is feasible and recommended for further development in advanced gastric cancer.

  18. Advanced numerical methods for three dimensional two-phase flow calculations

    Energy Technology Data Exchange (ETDEWEB)

    Toumi, I. [Laboratoire d`Etudes Thermiques des Reacteurs, Gif sur Yvette (France); Caruge, D. [Institut de Protection et de Surete Nucleaire, Fontenay aux Roses (France)

    1997-07-01

    This paper is devoted to new numerical methods developed for both one and three dimensional two-phase flow calculations. These methods are finite volume numerical methods and are based on the use of Approximate Riemann Solvers concepts to define convective fluxes versus mean cell quantities. The first part of the paper presents the numerical method for a one dimensional hyperbolic two-fluid model including differential terms as added mass and interface pressure. This numerical solution scheme makes use of the Riemann problem solution to define backward and forward differencing to approximate spatial derivatives. The construction of this approximate Riemann solver uses an extension of Roe`s method that has been successfully used to solve gas dynamic equations. As far as the two-fluid model is hyperbolic, this numerical method seems very efficient for the numerical solution of two-phase flow problems. The scheme was applied both to shock tube problems and to standard tests for two-fluid computer codes. The second part describes the numerical method in the three dimensional case. The authors discuss also some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. Such a scheme is not implemented in a thermal-hydraulic computer code devoted to 3-D steady-state and transient computations. Some results obtained for Pressurised Water Reactors concerning upper plenum calculations and a steady state flow in the core with rod bow effect evaluation are presented. In practice these new numerical methods have proved to be stable on non staggered grids and capable of generating accurate non oscillating solutions for two-phase flow calculations.

  19. Advanced numerical methods for three dimensional two-phase flow calculations

    International Nuclear Information System (INIS)

    Toumi, I.; Caruge, D.

    1997-01-01

    This paper is devoted to new numerical methods developed for both one and three dimensional two-phase flow calculations. These methods are finite volume numerical methods and are based on the use of Approximate Riemann Solvers concepts to define convective fluxes versus mean cell quantities. The first part of the paper presents the numerical method for a one dimensional hyperbolic two-fluid model including differential terms as added mass and interface pressure. This numerical solution scheme makes use of the Riemann problem solution to define backward and forward differencing to approximate spatial derivatives. The construction of this approximate Riemann solver uses an extension of Roe's method that has been successfully used to solve gas dynamic equations. As far as the two-fluid model is hyperbolic, this numerical method seems very efficient for the numerical solution of two-phase flow problems. The scheme was applied both to shock tube problems and to standard tests for two-fluid computer codes. The second part describes the numerical method in the three dimensional case. The authors discuss also some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. Such a scheme is not implemented in a thermal-hydraulic computer code devoted to 3-D steady-state and transient computations. Some results obtained for Pressurised Water Reactors concerning upper plenum calculations and a steady state flow in the core with rod bow effect evaluation are presented. In practice these new numerical methods have proved to be stable on non staggered grids and capable of generating accurate non oscillating solutions for two-phase flow calculations

  20. Engineering development of advanced coal-fired low-emissions boiler system. Phase II subsystem test design and plan - an addendum to the Phase II RD & T Plan

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-01

    Shortly after the year 2000 it is expected that new generating plants will be needed to meet the growing demand for electricity and to replace the aging plants that are nearing the end of their useful service life. The plants of the future will need to be extremely clean, highly efficient and economical. Continuing concerns over acid rain, air toxics, global climate changes, ozone depletion and solid waste disposal are expected to further then regulations. In the late 1980`s it was commonly believed that coal-fired power plants of the future would incorporate either some form of Integrated Gasification Combined Cycle (IGCC) or first generation Pressurized Fluidized Bed Combustion (PFBS) technologies. However, recent advances In emission control techniques at reduced costs and auxiliary power requirements coupled with significant improvements In steam turbine and cycle design have clearly indicated that pulverized coal technology can continue to be competitive In both cost and performance. In recognition of the competitive potential for advanced pulverized coal-fired systems with other emerging advanced coal-fired technologies, DOE`s Pittsburgh Energy Technology Center (PETC) began a research and development initiative In late 1990 named, Combustion 2000, with the intention of preserving and expanding coal as a principal fuel In the Generation of electrical power. The project was designed for two stages of commercialization, the nearer-term Low Emission Boiler System (LEBS) program, and for the future, the High Performance Power System (HIPPS) program. B&W is participating In the LEBS program.

  1. Advanced Structural Health Monitoring System for Comprehensive Real-Time Vehicle Characterization, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — In providing an innovative solution to improving information technologies and health management systems, AGNC is proposing a significant technological achievement...

  2. Advanced numerical methods for three dimensional two-phase flow calculations in PWR

    International Nuclear Information System (INIS)

    Toumi, I.; Gallo, D.; Royer, E.

    1997-01-01

    This paper is devoted to new numerical methods developed for three dimensional two-phase flow calculations. These methods are finite volume numerical methods. They are based on an extension of Roe's approximate Riemann solver to define convective fluxes versus mean cell quantities. To go forward in time, a linearized conservative implicit integrating step is used, together with a Newton iterative method. We also present here some improvements performed to obtain a fully implicit solution method that provides fast running steady state calculations. This kind of numerical method, which is widely used for fluid dynamic calculations, is proved to be very efficient for the numerical solution to two-phase flow problems. This numerical method has been implemented for the three dimensional thermal-hydraulic code FLICA-4 which is mainly dedicated to core thermal-hydraulic transient and steady-state analysis. Hereafter, we will also find some results obtained for the EPR reactor running in a steady-state at 60% of nominal power with 3 pumps out of 4, and a thermal-hydraulic core analysis for a 1300 MW PWR at low flow steam-line-break conditions. (author)

  3. A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.

    Science.gov (United States)

    Goncalves, Priscila H; Heilbrun, Lance K; Barrett, Michael T; Kummar, Shivaani; Hansen, Aaron R; Siu, Lillian L; Piekarz, Richard L; Sukari, Ammar W; Chao, Joseph; Pilat, Mary Jo; Smith, Daryn W; Casetta, Lindsay; Boerner, Scott A; Chen, Alice; Lenkiewicz, Elizabeth; Malasi, Smriti; LoRusso, Patricia M

    2017-05-16

    Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. Thirty patients were enrolled. Median age of patients was 53 years (range 21-73). Median number of cycles was 5 (range 1-66). Lymphopenia (n = 5), hypertension (n = 3), oral pain (n = 2), thromboembolic events (n = 2) and fatigue (n = 2) were the only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven patients were dose reduced secondary to drug-related AEs. Two patients had a partial response (PR), with response durations of 53 and 7.2 months. One patient had a minor response with a decrease in ascites (for 19 cycles). Stable disease was the best response in 27 patients. Targeted and WES of 8 patients in this trial identified mutations in chromatin remodeling genes highlighting the role of the epigenome in ACC. Vorinostat demonstrated efficacy in patients with ACC supporting the inclusion of HDACi in future studies to treat ACC.

  4. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2015-02-01

    Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright light duration?

    Science.gov (United States)

    Crowley, Stephanie J.; Eastman, Charmane I.

    2015-01-01

    OBJECTIVE Efficient treatments to phase advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS Fifty adults (27 males) aged 25.9±5.1 years participated. Sleep/dark was advanced 1 hour/day for 3 treatment days. Participants took 0.5 mg melatonin 5 hours before baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright light (~5000 lux) patterns upon waking each morning: four 30-minute exposures separated by 30 minutes of room light (2 h group); four 15-minute exposures separated by 45 minutes of room light (1 h group), and one 30-minute exposure (0.5 h group). Dim light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS Compared to the 2 h group (phase shift=2.4±0.8 h), smaller phase advance shifts were seen in the 1 h (1.7±0.7 h) and 0.5 h (1.8±0.8 h) groups. The 2-hour pattern produced the largest phase advance; however, the single 30-minute bright light exposure was as effective as 1 hour of bright light spread over 3.25 h, and produced 75% of the phase shift observed with 2 hours of bright light. CONCLUSIONS A 30-minute morning bright light exposure with afternoon melatonin is an efficient treatment to phase advance human circadian rhythms. PMID:25620199

  6. An advanced three-phase physical, experimental and numerical method for tsunami induced boulder transport

    Science.gov (United States)

    Oetjen, Jan; Engel, Max; Prasad Pudasaini, Shiva; Schüttrumpf, Holger; Brückner, Helmut

    2017-04-01

    Coasts around the world are affected by high-energy wave events like storm surges or tsunamis depending on their regional climatological and geological settings. By focusing on tsunami impacts, we combine the abilities and experiences of different scientific fields aiming at improved insights of near- and onshore tsunami hydrodynamics. We investigate the transport of coarse clasts - so called boulders - due to tsunami impacts by a multi-methodology approach of numerical modelling, laboratory experiments, and sedimentary field records. Coupled numerical hydrodynamic and boulder transport models (BTM) are widely applied for analysing the impact characteristics of the transport by tsunami, such as wave height and flow velocity. Numerical models able to simulate past tsunami events and the corresponding boulder transport patterns with high accuracy and acceptable computational effort can be utilized as powerful forecasting models predicting the impact of a coast approaching tsunami. We have conducted small-scale physical experiments in the tilting flume with real shaped boulder models. Utilizing the structure from motion technique (Westoby et al., 2012) we reconstructed real boulders from a field study on the Island of Bonaire (Lesser Antilles, Caribbean Sea, Engel & May, 2012). The obtained three-dimensional boulder meshes are utilized for creating downscaled replica of the real boulder for physical experiments. The results of the irregular shaped boulder are compared to experiments with regular shaped boulder models to achieve a better insight about the shape related influence on transport patterns. The numerical model is based on the general two-phase mass flow model by Pudasaini (2012) enhanced for boulder transport simulations. The boulder is implemented using the immersed boundary technique (Peskin, 2002) and the direct forcing approach. In this method Cartesian grids (fluid and particle phase) and Lagrangian meshes (boulder) are combined. By applying the

  7. [Active surveillance for prostate cancer: usefulness of endorectal MR at 1.5 Tesla with pelvic phased array coil in detecting significant tumors].

    Science.gov (United States)

    Luyckx, F; Hallouin, P; Barré, C; Aillet, G; Chauveau, P; Hétet, J-F; Bouchot, O; Rigaud, J

    2011-02-01

    To describe and assess MRI signs of significant tumor in a series of patients who all underwent radical prostatectomy and also fulfilled criteria to choose active surveillance according to French "SurAcaP" protocol. The clinical reports of 681 consecutive patients operated on for prostate cancer between 2002 and 2007 were reviewed retrospectively. All patients had endorectal MR (1.5 Tesla) with pelvic phased array coil. (1.5 T erMR PPA). Sixty-one patients (8.9%) fulfilled "SurAcaP" protocol criteria. Preoperative data (MR+core biopsy) were assessed by comparison to whole-mount step section pathology. 85.3% of the 61 patients entering SurAcaP protocol had significant tumor at pathology. (Non Organ Confined Disease (Non OCD)=8.2%, Gleason sum score>6=39.2%). A new exclusion criterion has been assessed: T3MRI±NPS>1 as a predictor tool of significant tumor. ("T3MRI±NPS>1"=Non OCD at MR±number of positive sextants involved in tumor at MR and/or Core Biopsy > to 1). Sensitivity, specificity, PPV, NPV of the criterion "T3MRI±NPS>1" in predicting significant tumor were, respectively: 77%, 33%, 86%, 20%. Adding this criterion to other criteria of the "SurAcaP" protocol could allow the exclusion of all Non OCD, and a decrease in Gleason sum Score>6 rates (20%). Endorectal MR at 1.5 Tesla with pelvic-phased array coil should be considered when selecting patients for active surveillance in the management of prostate cancer. A criterion based upon MR and core biopsy findings, called "T3MR±NSP>1" may represent an exclusion citeria due to its ability to predict significant tumor. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  8. Exploitation of Digital Filters to Advance the Single-Phase T/4 Delay PLL System

    DEFF Research Database (Denmark)

    Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede

    2016-01-01

    will violate this design rule and it can become a major challenge for digital controllers. To deal with the above issue, this paper first exploits a virtual unit delay (z_v^-1) to emulate the viable sampling behavior in practical digital signal processors with a fixed sampling rate. This exploitation......With the development of digital signal processing technologies, control and monitoring of power electronics conversion systems have been evolving to become fully digital. As the basic element in the design and analysis phase of digital controllers or filters, a number of unit delays (z^-1) have...... been employed, e.g., in a cascaded structure. Practically, the number of unit delays is designed as an integer, which is related to the sampling frequency (e.g., 50 Hz). More common, the sampling frequency is fixed during operation for simplicity and design. Hence, any disturbance in the ac signal...

  9. Advances in simulating non-congruent phase transitions of hyperstoichiometric uranium dioxide fuel

    International Nuclear Information System (INIS)

    Welland, M.J.; Thompson, W.T.; Lewis, B.J.

    2007-01-01

    A model is being developed to simulate UO 2 at very high temperatures incorporating the effects of non-congruent phase transitions. In particular, the melting transformation and the possible 'Λ-transition' is being investigated to help support the design and analysis of experimental work being conducted as part of nuclear safety research. This work includes the interpretation of the behaviour of operating CANDU fuel under upset conditions, where centerline melting may potentially occur (particularly if the fuel is oxidized). The model presented here numerically solves a system of coupled nonlinear differential equations as derived from fundamental principles. The results of the model present here compare well against laser flash experiments in recently published literature. (author)

  10. Ursodeoxycholic acid in advanced polycystic liver disease: A phase 2 multicenter randomized controlled trial.

    Science.gov (United States)

    D'Agnolo, Hedwig M A; Kievit, Wietske; Takkenberg, R Bart; Riaño, Ioana; Bujanda, Luis; Neijenhuis, Myrte K; Brunenberg, Ellen J L; Beuers, Ulrich; Banales, Jesus M; Drenth, Joost P H

    2016-09-01

    Ursodeoxycholic acid (UDCA) inhibits proliferation of polycystic human cholangiocytes in vitro and hepatic cystogenesis in a rat model of polycystic liver disease (PLD) in vivo. Our aim was to test whether UDCA may beneficially affect liver volume in patients with advanced PLD. We conducted an international, multicenter, randomized controlled trial in symptomatic PLD patients from three tertiary referral centers. Patients with PLD and total liver volume (TLV) ⩾2500ml were randomly assigned to UDCA treatment (15-20mg/kg/day) for 24weeks, or to no treatment. Primary endpoint was proportional change in TLV. Secondary endpoints were change in symptoms and health-related quality of life. We performed a post-hoc analysis of the effect of UDCA on liver cyst volume (LCV). We included 34 patients and were able to assess primary endpoint in 32 patients, 16 with autosomal dominant polycystic kidney disease (ADPKD) and 16 with autosomal dominant polycystic liver disease (ADPLD). Proportional TLV increased by 4.6±7.7% (mean TLV increased from 6697ml to 6954ml) after 24weeks of UDCA treatment compared to 3.1±3.8% (mean TLV increased from 5512ml to 5724ml) in the control group (p=0.493). LCV was not different after 24weeks between controls and UDCA treated patients (p=0.848). However, UDCA inhibited LCV growth in ADPKD patients compared to ADPKD controls (p=0.049). UDCA administration for 24weeks did not reduce TLV in advanced PLD, but UDCA reduced LCV growth in ADPKD patients. Future studies might explore whether ADPKD and ADPLD patients respond differently to UDCA treatment. Current therapies for polycystic liver disease are invasive and have high recurrence risks. Our trial showed that the drug, ursodeoxycholic acid, was not able to reduce liver volume in patients with polycystic liver disease. However, a subgroup analysis in patients that have kidney cysts as well showed that liver cyst volume growth was reduced in patients who received ursodeoxycholic acid in comparison

  11. UTILITY ADVANCED TURBINE SYSTEMS (ATS) TECHNOLOGY READINESS TESTING PHASE 3 RESTRUCTURED (3R); TOPICAL

    International Nuclear Information System (INIS)

    Unknown

    1999-01-01

    In the early 90's GE recognized the need to introduce new technology to follow on to the ''F'' technology the Company introduced in 1988. By working with industry and DOE, GE helped shape the ATS program goal of demonstrating a gas turbine, combined-cycle system using natural gas as the primary fuel that achieves the following targets: system efficiency exceeding 60% lower heating value basis; environmental superiority under full-load operating conditions without the use of post-combustion emissions controls, environmental superiority includes limiting NO(sub 2) to less than 10 parts per mission by volume (dry basis) at 15% oxygen; busbar energy costs that are 10% less than current state-of-the-art turbine systems meeting the same environmental requirements; fuel-flexible designs operating on natural gas but also capable of being adapted to operate on coal-based, distillate, or biomass fuels; reliability-availability-maintainability (RAM) that is equivalent to modern advanced power generation systems; and commercial systems that could enter the market in the year 2000

  12. A phase I study of concurrent chemoradiotherapy and cetuximab for locally advanced esophageal cancer

    DEFF Research Database (Denmark)

    Holländer, Cecilie; Baeksgaard, Lene; Sorensen, Morten

    2012-01-01

    AIM: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of concurrent chemoradiotherapy and cetuximab in patients with non-resectable locally advanced esophageal cancer. PATIENTS AND METHODS: Escalating doses of oxaliplatin every second week and daily tegafur....../uracil were given concurrently with radiotherapy, 59.4 Gy in 33 fractions. Cetuximab was given on day 15 (400 mg/m(2)) and weekly (250 mg/m(2)) during radiotherapy. Fixed doses of oxaliplatin (130 mg/m(2)) and tegafur/uracil (300 mg/m(2)) were administered before, and after radiotherapy. RESULTS: Eleven...... patients were included in the study; two were excluded due to allergic reactions to cetuximab. In DL2 (tegafur/uracil 300 mg/m(2), oxaliplatin 30 mg/m(2)) two grade 3/4 fistula and one grade 3 neuropathy were observed. Six patients were enrolled in DL1 (tegafur/uracil 150 mg/m(2)/, oxaliplatin 30 mg/m(2...

  13. Investigations of the reflood-phase after a loss-of-coolant-accident of an advanced pressurized water reactor (APWR)

    International Nuclear Information System (INIS)

    Schumann, S.; Oldekop, W.

    1983-01-01

    Differences between a high converting advanced pressurized-water reactor (APWR) and a conventional PWR, which are relevant to the reflood-phase after LOCA are presented. The used code and its verification by PWR-reflood experiments is explained. Comparative calculations for APWR and PWR with several conservative assumptions for example cold-leg-injection only, yield nearly the same maximum midplane-temperatures for the average-channel. For the APWR, however, the upper half of the rod shows higher temperatures. Quenchfront and core-water-level increase more slowly. The differences in the reflood-thermohydraulics are analysed in detail. A conservative hot-channel calculation shows maximum temperatures of about 920 0 C. Finally the influence of conservative assumptions is described and the necessity of experiments pointed out. (orig.)

  14. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shang-Wen, E-mail: sjfchiou@gmail.com [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Lin, Li-Ching [Department of Radiation Oncology, Chi-Mei Hospital, Tainan, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Kuo, Yu-Cheng [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan (China); Liang, Ji-An [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Kuo, Chia-Chun [Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); Chiou, Jeng-Fong [Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  15. Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II study

    Directory of Open Access Journals (Sweden)

    Savage Paul

    2002-05-01

    Full Text Available Abstract Background 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate – leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. Methods Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate – 30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV – 500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil – 600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression. Results The median age was 64 yrs (34–84 and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. Conclusions This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin are in progress and may prove encouraging.

  16. The scrounge-atron: a phased approach to the advanced hydrotest facility utilizing proton radiography

    International Nuclear Information System (INIS)

    Alford, O.J.; Barnes, P.D. Jr.; Chargin, A.K.; Dekin, W.D.; Hartouni, E.P.; Hockman, J.; Hockman, J.N.; Ladran, A.S.; Libkind, M.A.; Moore, T.L.; Ohnuma, S.; Pastrnak, J.W.; Pico, R.E.; Ruggiero, A.G.; Souza, R.J.; Stoner, J.M.; Wilson, J.H.

    1999-01-01

    The Department of Energy has initiated its Stockpile Stewardship and Management Program (SSMP) to provide a single, integrated technical program for maintaining the continued safety and reliability of the nation's nuclear weapons stockpile in the absence of nuclear testing. Consistent with the SSMP, the Advanced Hydrotest Facility (AHF) has been conceived to provide improved radiographic imaging with multiple axes and multiple time frames. The AHF would be used to better understand the evolution of nuclear weapon primary implosion shape under normal and accident scenarios. There are three fundamental technologies currently under consideration for use on the AHF. These include linear induction acceleration, inductive-adder pulsed-power technology (both technologies using high current electron beams to produce an intense X-ray beam) and high-energy proton accelerators to produce a proton beam. The Scrounge-atron (a proton synchrotron) was conceived to be a relatively low cost demonstration of the viability of the third technology using bursts of energetic protons, magnetic lenses, and particle detectors to produce the radiographic image. In order for the Scrounge-atron to provide information useful for the AHF technology decision, the accelerator would have to be built as quickly and as economically as possible. These conditions can be met by scrounging parts from decommissioned accelerators across the country, especially the Main Ring at Fermilab. The Scrounge-atron is designed to meet the baseline parameters for single axis proton radiography: a 20 GeV proton beam of ten pulses, 10 11 protons each, spaced 250 ns apart

  17. Phase I Study of Daily Irinotecan as a Radiation Sensitizer for Locally Advanced Pancreatic Cancer

    International Nuclear Information System (INIS)

    Fouchardiere, Christelle de la; Negrier, Sylvie; Labrosse, Hugues; Martel Lafay, Isabelle; Desseigne, Francoise; Meeus, Pierre; Tavan, David; Petit-Laurent, Fabien; Rivoire, Michel; Perol, David; Carrie, Christian

    2010-01-01

    Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas. Methods and Materials: Between September 2000 and March 2008, 36 patients with histologically proven unresectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m 2 per day and then escalated by increments of 2 mg/m 2 every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperability was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists. Results: Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m 2 to 20 mg/m 2 per day). The maximum tolerated dose was determined to be 18 mg/m 2 per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery. Conclusions: The maximum tolerated dose of irinotecan is 18 mg/m 2 per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.

  18. Phase Equilibrium and Austenite Decomposition in Advanced High-Strength Medium-Mn Bainitic Steels

    Directory of Open Access Journals (Sweden)

    Adam Grajcar

    2016-10-01

    Full Text Available The work addresses the phase equilibrium analysis and austenite decomposition of two Nb-microalloyed medium-Mn steels containing 3% and 5% Mn. The pseudobinary Fe-C diagrams of the steels were calculated using Thermo-Calc. Thermodynamic calculations of the volume fraction evolution of microstructural constituents vs. temperature were carried out. The study comprised the determination of the time-temperature-transformation (TTT diagrams and continuous cooling transformation (CCT diagrams of the investigated steels. The diagrams were used to determine continuous and isothermal cooling paths suitable for production of bainite-based steels. It was found that the various Mn content strongly influences the hardenability of the steels and hence the austenite decomposition during cooling. The knowledge of CCT diagrams and the analysis of experimental dilatometric curves enabled to produce bainite-austenite mixtures in the thermomechanical simulator. Light microscopy (LM, scanning electron microscopy (SEM, and transmission electron microscopy (TEM were used to assess the effect of heat treatment on morphological details of produced multiphase microstructures.

  19. Investigation of vertical slug flow with advanced two-phase flow instrumentation

    International Nuclear Information System (INIS)

    Mi, Y.; Ishii, M.; Tsoukalas, L.H.

    2001-01-01

    Extensive experiments of vertical slug flow were carried out with an electromagnetic flowmeter and an impedance void-meter in an air-water two-phase experimental loop. The basic principles of these instruments in vertical slug flow measurements are discussed. Time series of the liquid velocity and the impedance were separated into two parts corresponding to the Taylor bubble and the liquid slug. Characteristics of slug flow, such as the void fractions, probabilities and lengths of the Taylor bubble and liquid slug, slug unit velocity, area-averaged liquid velocity, and liquid film velocity of the Taylor bubble tail, etc., were obtained. For the first time, the area-averaged liquid velocity of slug flow was revealed by the electromagnetic flowmeter. It is realized that the void fraction of the liquid slug is determined by the turbulent intensity due to the relative liquid motion between the Taylor bubble tail region and its wake region. A correlation of the void fraction of the liquid slug is developed based on experimental results obtained from a test section with 50.8 mm i.d. The results of this study suggest a promising improvement in understanding of vertical slug flow

  20. High-speed, low-damage grinding of advanced ceramics Phase 1. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Kovach, J.A. [Eaton Corp., Willoughby Hills, OH (United States). Mfg. Technologies Center; Malkin, S. [Univ. of Massachusetts (United States)

    1995-03-01

    In manufacture of structural ceramic components, grinding costs can comprise up to 80% of the entire manufacturing cost. Most of these costs arise from the conventional multi-step grinding process with numerous grinding wheels and additional capital equipment, perishable dressing tools, and labor. In an attempt to reduce structural ceramic grinding costs, a feasibility investigation was undertaken to develop a single step, roughing-finishing process suitable for producing high-quality silicon nitride ceramic parts at high material removal rates at lower cost than traditional, multi-stage grinding. This feasibility study employed combined use of laboratory grinding tests, mathematical grinding models, and characterization of resultant material surface condition. More specifically, this Phase 1 final report provides a technical overview of High-Speed, Low-Damage (HSLD) ceramic grinding and the conditions necessary to achieve the small grain depths of cut necessary for low damage grinding while operating at relatively high material removal rates. Particular issues addressed include determining effects of wheel speed and material removal rate on resulting mode of material removal (ductile or brittle fracture), limiting grinding forces, calculation of approximate grinding zone temperatures developed during HSLD grinding, and developing the experimental systems necessary for determining HSLD grinding energy partition relationships. In addition, practical considerations for production utilization of the HSLD process are also discussed.

  1. ADVANCED DIAGNOSTIC TECHNIQUES FOR THREE-PHASE SLURRY BUBBLE COLUMN REACTORS(SBCR)

    Energy Technology Data Exchange (ETDEWEB)

    M.H. Al-Dahhan; L.S. Fan; M.P. Dudukovic

    2002-07-25

    This report summarizes the accomplishment made during the third year of this cooperative research effort between Washington University, Ohio State University and Air Products and Chemicals. Data processing of the performed Computer Automated Radioactive Particle Tracking (CARPT) experiments in 6 inch column using air-water-glass beads (150 {micro}m) system has been completed. Experimental investigation of time averaged three phases distribution in air-Therminol LT-glass beads (150 {micro}m) system in 6 inch column has been executed. Data processing and analysis of all the performed Computed Tomography (CT) experiments have been completed, using the newly proposed CT/Overall gas holdup methodology. The hydrodynamics of air-Norpar 15-glass beads (150 {micro}m) have been investigated in 2 inch slurry bubble column using Dynamic Gas Disengagement (DGD), Pressure Drop fluctuations, and Fiber Optic Probe. To improve the design and scale-up of bubble column reactors, a correlation for overall gas holdup has been proposed based on Artificial Neural Network and Dimensional Analysis.

  2. Advanced Laser-Based Techniques for Gas-Phase Diagnostics in Combustion and Aerospace Engineering.

    Science.gov (United States)

    Ehn, Andreas; Zhu, Jiajian; Li, Xuesong; Kiefer, Johannes

    2017-03-01

    Gaining information of species, temperature, and velocity distributions in turbulent combustion and high-speed reactive flows is challenging, particularly for conducting measurements without influencing the experimental object itself. The use of optical and spectroscopic techniques, and in particular laser-based diagnostics, has shown outstanding abilities for performing non-intrusive in situ diagnostics. The development of instrumentation, such as robust lasers with high pulse energy, ultra-short pulse duration, and high repetition rate along with digitized cameras exhibiting high sensitivity, large dynamic range, and frame rates on the order of MHz, has opened up for temporally and spatially resolved volumetric measurements of extreme dynamics and complexities. The aim of this article is to present selected important laser-based techniques for gas-phase diagnostics focusing on their applications in combustion and aerospace engineering. Applicable laser-based techniques for investigations of turbulent flows and combustion such as planar laser-induced fluorescence, Raman and Rayleigh scattering, coherent anti-Stokes Raman scattering, laser-induced grating scattering, particle image velocimetry, laser Doppler anemometry, and tomographic imaging are reviewed and described with some background physics. In addition, demands on instrumentation are further discussed to give insight in the possibilities that are offered by laser flow diagnostics.

  3. Advances on the time differential three-phase-lag heat conduction model and major open issues

    Science.gov (United States)

    D'Apice, Ciro; Zampoli, Vittorio

    2017-07-01

    The main purpose of this short contribution is to summarize the recent achievements concerning the so-called time differential three-phase-lag heat conduction model, contextually focusing attention on some of the numerous open problems associated with such an attractive theory. After having briefly recalled the origin of the model at issue, the restrictions upon the delay times and the constitutive tensors able to make it thermodynamically consistent are recalled. Under these hypotheses, the investigation of the well-posedness issue has already provided important results in terms of uniqueness and continuous dependence of the solutions (even related to the thermoelastic case), as well as in terms of existence of a domain of influence of the assigned data in connection with the thermoelastic model. Finally, some of the main problems currently object of investigation are recalled, including the very challenging issues about the different possible choices of Taylor series expansion orders for the constitutive equation, the interaction of the model with energy processes that take place on the nanoscale, with multi-porous materials and with biological systems.

  4. Advanced far infrared blocked impurity band detectors based on germanium liquid phase epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Christopher Sean [Univ. of California, Berkeley, CA (United States)

    1998-05-01

    This research has shown that epilayers with residual impurity concentrations of 5 x 1013 cm-3 can be grown by producing the purest Pb available in the world. These epilayers have extremely low minority acceptor concentrations, which is ideal for fabrication of IR absorbing layers. The Pb LPE growth of Ge also has the advantageous property of gettering Cu from the epilayer and the substrate. Epilayers have been grown with intentional Sb doping for IR absorption on lightly doped substrates. This research has proven that properly working Ge BIB detectors can be fabricated from the liquid phase as long as pure enough solvents are available. The detectors have responded at proper wavelengths when reversed biased even though the response did not quite reach minimum wavenumbers. Optimization of the Sb doping concentration should further decrease the photoionization energy of these detectors. Ge BIB detectors have been fabricated that respond to 60 cm-1 with low responsivity. Through reduction of the minority residual impurities, detector performance has reached responsivities of 1 A/W. These detectors have exhibited quantum efficiency and NEP values that rival conventional photoconductors and are expected to provide a much more sensitive tool for new scientific discoveries in a number of fields, including solid state studies, astronomy, and cosmology.

  5. A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer

    International Nuclear Information System (INIS)

    Geara, Fady B; Shamseddine, Ali; Khalil, Ali; Abboud, Mirna; Charafeddine, Maya; Seoud, Muhieddine

    2010-01-01

    This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma. Between May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m 2 Cisplatin (group I; 16 patients) or 50 mg/m 2 paclitaxel (group II; 15 patients) concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy) for group I and 66 Gy (range: 40-98 Gy) for group II. Median follow-up time was 46 months. Patient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44%) of group I and 8 patients (53%) of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively. This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix

  6. Phase II trial of cisplatin in advanced or recurrent cancer of the vagina: a Gynecologic Oncology Group Study.

    Science.gov (United States)

    Thigpen, J T; Blessing, J A; Homesley, H D; Berek, J S; Creasman, W T

    1986-01-01

    Twenty-six patients with advanced or recurrent cancer of the vagina no longer amenable to control with surgery and/or radiotherapy were entered into a phase II study of cisplatin 50 mg/m2 intravenously every 3 weeks. Two were deemed ineligible because of a primary site of origin other than vagina. Two were deemed inevaluable, one because of the lack of measurable disease and the other because she never received drug. The remaining 22 included a variety of histologies (16 squamous cell carcinomas, 2 adenosquamous carcinomas, 1 clear cell carcinoma, 1 leiomyosarcoma, and 2 carcinomas not otherwise specified). One complete responder was observed among the 16 patients with squamous cell carcinoma. Adverse effects were tolerable and were essentially those reported in other series. These results suggest that cisplatin has insignificant activity in advanced or recurrent squamous cell carcinoma of the vagina at least at the dose and schedule tested. No comment can be made regarding the activity of cisplatin in other histologies.

  7. First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Barry H. Smith

    2016-01-01

    Full Text Available Purpose Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival, which is the secondary objective. Methods Thirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075. Serial physical examinations, laboratory testing, and PET-CT imaging were performed before and three months after each implant. Results RMBs were well tolerated at both dose levels (mean 660.9 per implant. AEs were (Grade 1/2 with no treatment-related SAEs. Conclusion The data support the safety of RMB therapy in advanced-malignancy patients, and the preliminary evidence for their potential efficacy is encouraging. A Phase 2 efficacy trial is ongoing.

  8. A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas

    International Nuclear Information System (INIS)

    Medina, Jose Antonio; Rueda, Antonio; Sacchetti de Pasos, Antonio; Contreras, Jorge; Cobo, Manuel; Moreno, Paloma; Benavides, Manuel; Villanueva, Asuncion; Alba, Emilio

    2006-01-01

    Background and purpose: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. Material and methods: A total of 94 patients (median age, 58 years) with UICC stage III (n=19) and IV (n=75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m 2 weekly, for the first 4 weeks. Results: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. Conclusions: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data

  9. Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Arrieta, Oscar; Blake, Mónika; Mata-Moya, María Dolores de la; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

    2014-01-01

    Background: Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods: This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Results: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8–18.2), and the median overall survival was 26.9 months (95% CI, 15.3–38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). Conclusions: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings

  10. Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO)

    International Nuclear Information System (INIS)

    Lindemann, Kristina; Nordstrøm, Britta; Malander, Susanne; Christensen, Rene D; Mirza, Mansoor R; Kristensen, Gunnar B; Aavall-Lundqvist, Elisabeth; Vergote, Ignace; Rosenberg, Per; Boman, Karin

    2014-01-01

    We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma. We performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients. Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated. Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients. Trial identification number (Clinical Trials.gov): http://www.clinicaltrials.gov/NCT01965080. Nordic Society of Gynecological Oncology: NSGO–EC–0302. EudraCT number: 2004-001103-35

  11. A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors.

    Science.gov (United States)

    Schelman, William R; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M; Ivy, Percy; Wilding, George; Traynor, Anne M

    2009-05-01

    To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine administered in combination with doxorubicin. Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine 25 mg/m(2). PK analysis was performed at various time-points before and after treatment. Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Pretreated patients with advanced malignancies can tolerate the combination of Triapine and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine 25 mg/m(2) on days 1-4 of a 21-day cycle.

  12. Brain-wave measures of workload in advanced cockpits: The transition of technology from laboratory to cockpit simulator, phase 2

    Science.gov (United States)

    Horst, Richard L.; Mahaffey, David L.; Munson, Robert C.

    1989-01-01

    The present Phase 2 small business innovation research study was designed to address issues related to scalp-recorded event-related potential (ERP) indices of mental workload and to transition this technology from the laboratory to cockpit simulator environments for use as a systems engineering tool. The project involved five main tasks: (1) Two laboratory studies confirmed the generality of the ERP indices of workload obtained in the Phase 1 study and revealed two additional ERP components related to workload. (2) A task analysis' of flight scenarios and pilot tasks in the Advanced Concepts Flight Simulator (ACFS) defined cockpit events (i.e., displays, messages, alarms) that would be expected to elicit ERPs related to workload. (3) Software was developed to support ERP data analysis. An existing ARD-proprietary package of ERP data analysis routines was upgraded, new graphics routines were developed to enhance interactive data analysis, and routines were developed to compare alternative single-trial analysis techniques using simulated ERP data. (4) Working in conjunction with NASA Langley research scientists and simulator engineers, preparations were made for an ACFS validation study of ERP measures of workload. (5) A design specification was developed for a general purpose, computerized, workload assessment system that can function in simulators such as the ACFS.

  13. Development of the advanced phased array UT technique for accurate sizing of cracks in the nozzle welding

    International Nuclear Information System (INIS)

    Nishida, Jun-ichiro; Kawanami, Seiichi; Ideo, Mitsushi; Matsuura, Takayuki; Chigusa, Naoki; Hirano, Shinro; Sera, Takehiko

    2010-01-01

    Recently, preventive maintenance tasks for welding of safe-end nozzles of reactor vessels and steam generators of PWRs in Japan had been carried out sequentially. Before the maintenance tasks, inspection services were carried out and several crack indications were found by eddy current testing (ECT). These indications were found in the welding which made by 600 series nickel base alloy and evaluated as stress corrosion cracks which were oriented to the axial direction of the nozzle. Then investigations to evaluate the depth of cracks were carried out by ultrasonic testing (UT) from inner surface of the nozzles. However they were difficult to evaluate the depth of cracks due to the high attenuation of the ultrasonic propagation caused by large grain structure of welding. And also it was required high resolution near surface region for accurate sizing. Therefore development of advanced phased array UT techniques specialized for the sizing at this portion was carried out. This paper reports the development status and verification test results. Firstly simulations of the ultrasonic propagation in the welding were carried out to optimize beam profiles of phased array probes. Next prototype probes were manufactured and verification tests were conducted to evaluate the accuracy of depth sizing. It is shown that the developed techniques have high sizing accuracy for artificial stress corrosion cracks in the welding. (author)

  14. Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

    International Nuclear Information System (INIS)

    Anthoney, D Alan; Miwa, Masanori; Twelves, Christopher; Evans, TRJ; Naik, Jay; MacPherson, Iain RJ; Crawford, Donna; Hartley, John M; Hartley, Janet A; Saito, Tomohisa; Abe, Masaichi; Jones, Keith

    2012-01-01

    A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m 2 . MTD was 10 mg/m 2 ; DLTs at 12 (2/4 patients) and 10 mg/m 2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhoea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and C max from 1–10 mg/m 2 . Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. TP300 had predictable hematologic toxicity, and diarrhoea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage. EU-CTR2006-001345-33

  15. Hot-working behavior of an advanced intermetallic multi-phase γ-TiAl based alloy

    Energy Technology Data Exchange (ETDEWEB)

    Schwaighofer, Emanuel, E-mail: emanuel.schwaighofer@unileoben.ac.at [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Roseggerstr. 12, A-8700 Leoben (Austria); Clemens, Helmut [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Roseggerstr. 12, A-8700 Leoben (Austria); Lindemann, Janny [Chair of Physical Metallurgy and Materials Technology, Brandenburg University of Technology, Konrad-Wachsmann-Allee 17, D-03046 Cottbus (Germany); GfE Fremat GmbH, Lessingstr. 41, D-09599 Freiberg (Germany); Stark, Andreas [Institute of Materials Research, Helmholtz-Zentrum Geesthacht, Max-Planck-Str. 1, D-21502 Geesthacht (Germany); Mayer, Svea [Department of Physical Metallurgy and Materials Testing, Montanuniversität Leoben, Roseggerstr. 12, A-8700 Leoben (Austria)

    2014-09-22

    New high-performance engine concepts for aerospace and automotive application enforce the development of lightweight intermetallic γ-TiAl based alloys with increased high-temperature capability above 750 °C. Besides an increased creep resistance, the alloy system must exhibit sufficient hot-workability. However, the majority of current high-creep resistant γ-TiAl based alloys suffer from poor workability, whereby grain refinement and microstructure control during hot-working are key factors to ensure a final microstructure with sufficient ductility and tolerance against brittle failure below the brittle-to-ductile transition temperature. Therefore, a new and advanced β-solidifying γ-TiAl based alloy, a so-called TNM alloy with a composition of Ti–43Al–4Nb–1Mo–0.1B (at%) and minor additions of C and Si, is investigated by means of uniaxial compressive hot-deformation tests performed with a Gleeble 3500 simulator within a temperature range of 1150–1300 °C and a strain rate regime of 0.005–0.5 s{sup −1} up to a true deformation of 0.9. The occurring mechanisms during hot-working were decoded by ensuing constitutive modeling of the flow curves by a novel phase field region-specific surface fitting approach via a hyperbolic-sine law as well as by evaluation through processing maps combined with microstructural post-analysis to determine a safe hot-working window of the refined TNM alloy. Complementary, in situ high energy X-ray diffraction experiments in combination with an adapted quenching and deformation dilatometer were conducted for a deeper insight about the deformation behavior of the alloy, i.e. phase fractions and texture evolution as well as temperature uncertainties arising during isothermal and non-isothermal compression. It was found that the presence of β-phase and the contribution of particle stimulated nucleation of ζ-Ti{sub 5}Si{sub 3} silicides and h-type carbides Ti{sub 2}AlC enhance the dynamic recrystallization behavior during

  16. Hot-working behavior of an advanced intermetallic multi-phase γ-TiAl based alloy

    International Nuclear Information System (INIS)

    Schwaighofer, Emanuel; Clemens, Helmut; Lindemann, Janny; Stark, Andreas; Mayer, Svea

    2014-01-01

    New high-performance engine concepts for aerospace and automotive application enforce the development of lightweight intermetallic γ-TiAl based alloys with increased high-temperature capability above 750 °C. Besides an increased creep resistance, the alloy system must exhibit sufficient hot-workability. However, the majority of current high-creep resistant γ-TiAl based alloys suffer from poor workability, whereby grain refinement and microstructure control during hot-working are key factors to ensure a final microstructure with sufficient ductility and tolerance against brittle failure below the brittle-to-ductile transition temperature. Therefore, a new and advanced β-solidifying γ-TiAl based alloy, a so-called TNM alloy with a composition of Ti–43Al–4Nb–1Mo–0.1B (at%) and minor additions of C and Si, is investigated by means of uniaxial compressive hot-deformation tests performed with a Gleeble 3500 simulator within a temperature range of 1150–1300 °C and a strain rate regime of 0.005–0.5 s −1 up to a true deformation of 0.9. The occurring mechanisms during hot-working were decoded by ensuing constitutive modeling of the flow curves by a novel phase field region-specific surface fitting approach via a hyperbolic-sine law as well as by evaluation through processing maps combined with microstructural post-analysis to determine a safe hot-working window of the refined TNM alloy. Complementary, in situ high energy X-ray diffraction experiments in combination with an adapted quenching and deformation dilatometer were conducted for a deeper insight about the deformation behavior of the alloy, i.e. phase fractions and texture evolution as well as temperature uncertainties arising during isothermal and non-isothermal compression. It was found that the presence of β-phase and the contribution of particle stimulated nucleation of ζ-Ti 5 Si 3 silicides and h-type carbides Ti 2 AlC enhance the dynamic recrystallization behavior during deformation within

  17. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma.

    Science.gov (United States)

    Escudier, Bernard; Sharma, Padmanee; McDermott, David F; George, Saby; Hammers, Hans J; Srinivas, Sandhya; Tykodi, Scott S; Sosman, Jeffrey A; Procopio, Giuseppe; Plimack, Elizabeth R; Castellano, Daniel; Gurney, Howard; Donskov, Frede; Peltola, Katriina; Wagstaff, John; Gauler, Thomas C; Ueda, Takeshi; Zhao, Huanyu; Waxman, Ian M; Motzer, Robert J

    2017-12-01

    The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Nivolumab 3mg/kg every 2 wk or everolimus 10mg once daily. The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  18. The role of the Istituto Superiore di Sanità as the competent authority for Phase I trials in the translation of advanced therapies

    Directory of Open Access Journals (Sweden)

    Patrizia Popoli

    2011-01-01

    Full Text Available Advanced therapy medicinal products (ATMP can offer new, effective therapeutic options for the treatment of severe illnesses, including cancer, neurodegenerative and cardiovascular diseases. Translation of advanced therapies to the clinic has been slow despite significant academic research from academia and foundations. The implementation of 2001/20 Directive in Italy established that the development of an ATMP should follow the GXP rules - good manufacturing practice (GMP for production, good laboratory practice (GLP for non clinical safety studies and good clinical practice (GCP for clinical trials. The high costs of GCP application and the needs for GMP facilities are perceived as the most important bottlenecks for the development of ATMP. Here it is pointed out that a strategic cooperation between different actors (academia, industry and experts in regulatory issues is strongly needed. In particular, it is highlighted that the Istituto Superiore di Sanità, as the competent authority for the authorization of Phase I clinical trials, has a specific responsibility in fostering the translation of safe and effective therapies for human diseases.

  19. The role of the Istituto Superiore di Sanità as the competent authority for Phase I trials in the translation of advanced therapies.

    Science.gov (United States)

    Popoli, Patrizia; Cometa, Maria Francesca; Fabi, Fulvia; Meneguz, Annarita

    2011-01-01

    Advanced therapy medicinal products (ATMP) can offer new, effective therapeutic options for the treatment of severe illnesses, including cancer, neurodegenerative and cardiovascular diseases. Translation of advanced therapies to the clinic has been slow despite significant academic research from academia and foundations. The implementation of 2001/20 Directive in Italy established that the development of an ATMP should follow the GXP rules - good manufacturing practice (GMP) for production, good laboratory practice (GLP) for non clinical safety studies and good clinical practice (GCP) for clinical trials. The high costs of GCP application and the needs for GMP facilities are perceived as the most important bottlenecks for the development of ATMP. Here it is pointed out that a strategic cooperation between different actors (academia, industry and experts in regulatory issues) is strongly needed. In particular, it is highlighted that the Istituto Superiore di Sanità, as the competent authority for the authorization of Phase I clinical trials, has a specific responsibility in fostering the translation of safe and effective therapies for human diseases.

  20. A review of modern advances in analyses and applications of single-phase natural circulation loop in nuclear thermal hydraulics

    International Nuclear Information System (INIS)

    Basu, Dipankar N.; Bhattacharyya, Souvik; Das, P.K.

    2014-01-01

    Highlights: • Comprehensive review of state-of-the-art on single-phase natural circulation loops. • Detailed discussion on growth in solar thermal system and nuclear thermal hydraulics. • Systematic development in scaling methodologies for fabrication of test facilities. • Importance of numerical modeling schemes for stability assessment using 1-D codes. • Appraisal of current trend of research and possible future directions. - Abstract: A comprehensive review of single-phase natural circulation loop (NCL) is presented here. Relevant literature reported since the later part of 1980s has been meticulously surveyed, with occasional obligatory reference to a few pioneering studies originating prior to that period, summarizing the key observations and the present trend of research. Development in the concept of buoyancy-induced flow is discussed, with introduction to flow initiation in an NCL due to instability. Detailed discussion on modern advancement in important application areas like solar thermal systems and nuclear thermal hydraulics are presented, with separate analysis for various reactor designs working on natural circulation. Identification of scaling criteria for designing lab-scale experimental facilities has gone through a series of modification. A systematic analysis of the same is presented, considering the state-of-the-art knowledge base. Different approaches have been followed for modeling single-phase NCLs, including simplified Lorenz system mostly for toroidal loops, 1-D computational modeling for both steady-state and stability characterization and 3-D commercial system codes to have a better flow visualization. Methodical review of the relevant studies is presented following a systematic approach, to assess the gradual progression in understanding of the practical system. Brief appraisal of current research interest is reported, including the use of nanofluids for fluid property augmentation, marine reactors subjected to rolling waves

  1. A review of modern advances in analyses and applications of single-phase natural circulation loop in nuclear thermal hydraulics

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Dipankar N., E-mail: dipankar.n.basu@gmail.com [Department of Mechanical Engineering, Indian Institute of Technology Guwahati, Guwahati 781039 (India); Bhattacharyya, Souvik; Das, P.K. [Department of Mechanical Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302 (India)

    2014-12-15

    Highlights: • Comprehensive review of state-of-the-art on single-phase natural circulation loops. • Detailed discussion on growth in solar thermal system and nuclear thermal hydraulics. • Systematic development in scaling methodologies for fabrication of test facilities. • Importance of numerical modeling schemes for stability assessment using 1-D codes. • Appraisal of current trend of research and possible future directions. - Abstract: A comprehensive review of single-phase natural circulation loop (NCL) is presented here. Relevant literature reported since the later part of 1980s has been meticulously surveyed, with occasional obligatory reference to a few pioneering studies originating prior to that period, summarizing the key observations and the present trend of research. Development in the concept of buoyancy-induced flow is discussed, with introduction to flow initiation in an NCL due to instability. Detailed discussion on modern advancement in important application areas like solar thermal systems and nuclear thermal hydraulics are presented, with separate analysis for various reactor designs working on natural circulation. Identification of scaling criteria for designing lab-scale experimental facilities has gone through a series of modification. A systematic analysis of the same is presented, considering the state-of-the-art knowledge base. Different approaches have been followed for modeling single-phase NCLs, including simplified Lorenz system mostly for toroidal loops, 1-D computational modeling for both steady-state and stability characterization and 3-D commercial system codes to have a better flow visualization. Methodical review of the relevant studies is presented following a systematic approach, to assess the gradual progression in understanding of the practical system. Brief appraisal of current research interest is reported, including the use of nanofluids for fluid property augmentation, marine reactors subjected to rolling waves

  2. Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma.

    Science.gov (United States)

    Jasim, Sina; Suman, Vera J; Jimenez, Camilo; Harris, Pamela; Sideras, Kostandinos; Burton, Jill K; Worden, Francis Paul; Auchus, Richard J; Bible, Keith C

    2017-08-01

    Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers. To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL. This multicenter Phase II trial (MC107C) enrolled individuals  ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0-2, and measurable disease (response evaluation criteria in solid tumors 1.0). Pazopanib was administered in 28-day cycles, with the regimen ultimately being as follows: cycle 1: 400 mg daily on days 1-14, cycle 2: 800 mg daily on days 1-14, and then cycle 2 + : 800 mg daily on all days. The study was halted due to poor accrual. Seven patients were enrolled (05/2011-11/2014). One patient withdrew consent prior to treatment, leaving six evaluable patients. Treatment was discontinued, due to the following reasons: disease progression (4); withdrawal (1); and grade 4 (Takotsubo) cardiomyopathy (1). The median number of cycles administered was 4 (range: 2-29, total: 49). Four patients had >1 dose reduction due to the following reasons: fatigue (1), abnormal liver tests (2), hypertension and (Takotsubo) cardiomyopathy (1), and headaches (1). Common severe (Common Terminology Criteria for Adverse Events v3.0 grades 3-5) toxicities were as follows: hypertension (3/6), (Takotsubo) cardiomyopathy (2/6), diarrhea (1/6), fatigue (1/6), headache (1/6), and hematuria (1/6). One confirmed partial response was observed in PGL (17%, duration 2.4 years); median progression-free survival and overall survival were 6.5 and 14.8 months, respectively. Pazopanib has activity in Pheo/PGL requiring more study; optimal alpha- and beta-blockade are imperative pre-therapy in patients with secretory tumors, as risk of hypertension and cardiomyopathy are potentially life

  3. Cabozantinib Versus Everolimus in Patients with Advanced Renal Cell Carcinoma: Results of a Randomised Phase III Trial (METEOR

    Directory of Open Access Journals (Sweden)

    Toni Choueiri

    2015-11-01

    Full Text Available The METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma (RCC was reported by Prof Choueiri at the European Cancer Congress 2015. This presentation follows the publication in the New England Journal of Medicine of the METEOR trial back-to-back with the CheckMate 025 trial of nivolumab versus everolimus in the same patient setting. Excitingly, these trials demonstrated, for the first time, significant benefits over the standard of care for heavily pre-treated patients with advanced RCC. Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI aims to address the challenge of resistance to targeted therapy with TKIs. While the METEOR trial has not yet reached its final analysis of overall survival (OS, the clear progression-free survival (PFS benefit, acceptable safety profile, and similar tolerability to other TKIs shown by cabozantinib indicate that this represents a promising new treatment option for second-line or subsequent therapy for patients with advanced RCC.

  4. Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

    Science.gov (United States)

    Ahn, Peter H; Machtay, Mitchell; Anne, Pramila R; Cognetti, David; Keane, William M; Wuthrick, Evan; Dicker, Adam P; Axelrod, Rita S

    2018-05-01

    Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

  5. Solid-solid phase transformation via internal stress-induced virtual melting, significantly below the melting temperature. Application to HMX energetic crystal.

    Science.gov (United States)

    Levitas, Valery I; Henson, Bryan F; Smilowitz, Laura B; Asay, Blaine W

    2006-05-25

    We theoretically predict a new phenomenon, namely, that a solid-solid phase transformation (PT) with a large transformation strain can occur via internal stress-induced virtual melting along the interface at temperatures significantly (more than 100 K) below the melting temperature. We show that the energy of elastic stresses, induced by transformation strain, increases the driving force for melting and reduces the melting temperature. Immediately after melting, stresses relax and the unstable melt solidifies. Fast solidification in a thin layer leads to nanoscale cracking which does not affect the thermodynamics or kinetics of the solid-solid transformation. Thus, virtual melting represents a new mechanism of solid-solid PT, stress relaxation, and loss of coherence at a moving solid-solid interface. It also removes the athermal interface friction and deletes the thermomechanical memory of preceding cycles of the direct-reverse transformation. It is also found that nonhydrostatic compressive internal stresses promote melting in contrast to hydrostatic pressure. Sixteen theoretical predictions are in qualitative and quantitative agreement with experiments conducted on the PTs in the energetic crystal HMX. In particular, (a) the energy of internal stresses is sufficient to reduce the melting temperature from 551 to 430 K for the delta phase during the beta --> delta PT and from 520 to 400 K for the beta phase during the delta --> beta PT; (b) predicted activation energies for direct and reverse PTs coincide with corresponding melting energies of the beta and delta phases and with the experimental values; (c) the temperature dependence of the rate constant is determined by the heat of fusion, for both direct and reverse PTs; results b and c are obtained both for overall kinetics and for interface propagation; (d) considerable nanocracking, homogeneously distributed in the transformed material, accompanies the PT, as predicted by theory; (e) the nanocracking does not

  6. Does the Addition of Cetuximab to Radiochemotherapy Improve Outcome of Patients with Locally Advanced Rectal Cancer? Long-Term Results from Phase II Trials

    Directory of Open Access Journals (Sweden)

    M. Kripp

    2015-01-01

    Full Text Available Purpose. The addition of cetuximab to radiochemotherapy (RCT failed to improve complete response rates in locally advanced rectal cancer (LARC. We report the long-term results in patients treated within two sequential clinical trials. Methods. Patients receiving neoadjuvant RCT using capecitabine and irinotecan (CapIri within a phase I/II trial or CapIri + cetuximab within a phase II trial were evaluated for analysis of disease-free survival (DFS and overall survival (OS. KRAS exon 2 mutational status had been analyzed in patients receiving cetuximab. Results. 37 patients from the CapIri trial and 49 patients from the CapIri-cetuximab treatment group were evaluable. Median follow-up time was 75.2 months. The 5-year DFS rate was 82% (CapIri and 79% (CapIri-cetuximab (P=0.62. The median OS was 127.4 months. 5-year OS was 73% for both groups (CapIri and CapIri-cetuximab (P=0.61. No significant difference in DFS (P=0.86 or OS (P=0.39 was noticed between patients receiving CapIri and those receiving CapIri-cetuximab with KRAS wild-type tumors. Conclusions. As the addition of cetuximab did not improve neither DFS nor OS it should not play a role in the perioperative treatment of patients with LARC, not even of patients with (KRAS WT tumors.

  7. Development of improved processing and evaluation methods for high reliability structural ceramics for advanced heat engine applications Phase II. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Pujari, V.J.; Tracey, D.M.; Foley, M.R. [and others

    1996-02-01

    The research program had as goals the development and demonstration of significant improvements in processing methods, process controls, and nondestructive evaluation (NDE) which can be commercially implemented to produce high reliability silicon nitride components for advanced heat engine applications at temperatures to 1370{degrees}C. In Phase I of the program a process was developed that resulted in a silicon nitride - 4 w% yttria HIP`ed material (NCX 5102) that displayed unprecedented strength and reliability. An average tensile strength of 1 GPa and a strength distribution following a 3-parameter Weibull distribution were demonstrated by testing several hundred buttonhead tensile specimens. The Phase II program focused on the development of methodology for colloidal consolidation producing green microstructure which minimizes downstream process problems such as drying, shrinkage, cracking, and part distortion during densification. Furthermore, the program focused on the extension of the process to gas pressure sinterable (GPS) compositions. Excellent results were obtained for the HIP composition processed for minimal density gradients, both with respect to room-temperature strength and high-temperature creep resistance. Complex component fabricability of this material was demonstrated by producing engine-vane prototypes. Strength data for the GPS material (NCX-5400) suggest that it ranks very high relative to other silicon nitride materials in terms of tensile/flexure strength ratio, a measure of volume quality. This high quality was derived from the closed-loop colloidal process employed in the program.

  8. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Terence, E-mail: trdtwk@nccs.com.sg [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Lim, Wan-Teck [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Ong, Whee-Sze; Tan, Sze-Huey [Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore (Singapore); Yip, Connie; Quah, Daniel [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Soo, Khee-Chee [Division of Surgical Oncology, National Cancer Centre Singapore (Singapore); Wee, Joseph [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore)

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  9. Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

    Directory of Open Access Journals (Sweden)

    Guetz S

    2017-02-01

    Full Text Available Sylvia Guetz,1,* Amanda Tufman,2,* Joachim von Pawel,3 Achim Rittmeyer,4 Astrid Borgmeier,2 Pierre Ferré,5 Birgit Edlich,6 Rudolf Maria Huber2 1Ev. Diakonissenkrankenhaus Leipzig, Leipzig, 2University Hospital Munich and Thoracic Oncology Centre Munich, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (DZL CPC-M, Munich, 3Asklepios Fachkliniken Muenchen-Gauting, Gauting, 4Lungenfachklinik Immenhausen, Immenhausen, Germany; 5Pierre Fabre Pharmaceuticals, Oncology Research and Development Center, Toulouse, France; 6Pierre Fabre Pharma GmbH, Freiburg, Germany *These authors contributed equally to this work Micro-abstract: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. Introduction: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine® Oral, NVBo in advanced non-small-cell lung cancer (NSCLC. Patients and methods: Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20–50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP, overall survival (OS and tolerability. Results: Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs. Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21

  10. The facilitating role of chemotherapy in the palliative phase of cancer: qualitative interviews with advanced cancer patients.

    Directory of Open Access Journals (Sweden)

    Hilde M Buiting

    Full Text Available OBJECTIVE: To explore the extent to which patients have a directing role in decisions about chemotherapy in the palliative phase of cancer and (want to anticipate on the last stage of life. DESIGN: Qualitative interview study. METHODS: In depth-interviews with 15 patients with advanced colorectal or breast cancer at the medical oncology department in a Dutch teaching hospital; interviews were analysed following the principles of thematic content-analysis. RESULTS: All patients reported to know that the chemotherapy they received was with palliative intent. Most of them did not express the wish for information about (other treatment options and put great trust in their physicians' treatment advice. The more patients were aware of the severity of their disease, the more they seemed to 'live their life' in the present and enjoy things besides having cancer. Such living in the present seemed to be facilitated by the use of chemotherapy. Patients often considered the 'chemotherapy-free period' more stressful than periods when receiving chemotherapy despite their generally improved physical condition. Chemotherapy (regardless of side-effects seemed to shift patients' attention away from the approaching last stage of life. Interestingly, although patients often discussed advance care planning, they were reluctant to bring on end-of-life issues that bothered them at that specific moment. Expressing real interest in people 'as a person' was considered an important element of appropriate care. CONCLUSIONS: Fearing their approaching death, patients deliberately focus on living in the present. Active (chemotherapy treatment facilitates this focus, regardless of the perceived side-effects. However, if anxiety for what lies ahead is the underlying reason for treatment, efforts should be made in assisting patients to find other ways to cope with this fear. Simultaneously, such an approach may reduce the use of burdensome and sometimes costly treatment in the

  11. Advanced process control for solid fuel boilers. Phase 2; Avancerad processtyrning av fastbraensleeldade rostpannor. Etapp 2

    Energy Technology Data Exchange (ETDEWEB)

    Ehleskog, Rickard; Lundborg, Rickard; Schuster, Robert; Wrangensten, Lars [AaF-Energikonsult AB, Stockholm (Sweden)

    2002-04-01

    AaF-Energikonsult AB runs within the research programme 'Applied combustion technology' a bigger project under the title 'Possibilities to improved operation of forest-industrial bark boilers by optimised combustion control'. In the project several measures have been identified, that can help to improve the conditions favourable for the combustion and fluid dynamic, for four selected reference grate boilers and grate boilers in general. The boiler at Billerud's paper mill, which is underlying to this project in several ways, is now being rebuilt. During the modifications of the boiler the existing control system will be modified with modern technique to enable operation with low emissions. The new control system consists of several parts, of witch the IR-based ones for fuel input and grate feeding are two totally separated systems. The pressure of the dome, i.e. the effect of the boiler, is the most superior parameter, and is regulated with the combustion air. Amounts of secondary and tertiary air are quoted to the total combustion airflow. The primary oxygen level is primarily regulated with the tertiary air. But if this won't be done without the tertiary air to diverge from de defined working area, the secondary air will assist. The oxygen set point is constantly decreasing until the CO-level exceeds a defined level. Then, the set point will be momentary increased. CFD-calculations have been performed for the modified boiler in Karlsborg for two different loads. The simulations clearly show that the flue gases have a more even retention time in the modified boiler and that the flow pattern is significantly improved. However, concentration gradients of oxygen and temperature gradients still exist. The conclusion is that there is a potential for further improving of the air and flue gas control strategies. The following new control strategies are proposed in the project based on conventional analyse technology; If the furnace

  12. MO19390 (SAiL): bleeding events in a phase IV study of first-line bevacizumab with chemotherapy in patients with advanced non-squamous NSCLC.

    Science.gov (United States)

    Dansin, Eric; Cinieri, Saverio; Garrido, Pilar; Griesinger, Frank; Isla, Dolores; Koehler, Manfred; Kohlhaeufl, Martin

    2012-06-01

    The clinical benefit and safety profile associated with first-line bevacizumab with doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) was established in two large phase III studies, E4599 and AVAiL. SAiL, a single-arm phase IV study, was conducted to evaluate bevacizumab with a range of first-line chemotherapy regimens in a routine oncology practice setting. This analysis of the SAiL data was undertaken to specifically evaluate bleeding adverse events (AEs) in this study, and to explore potential associations between bleeding and baseline patient and disease characteristics. In total, 2212 patients were evaluated. Bleeding AEs (any grade) occurred in 38.2% of patients (grade ≥ 3 bleeding AEs: 3.6%). Grade ≥ 3 pulmonary hemorrhage and central nervous system bleeding events were observed in 0.7% and 0.1% of patients, respectively. The incidence of grade ≥ 3 bleeding AEs was comparable across patient subgroups defined by central tumor location, tumor cavitation, histology, concomitant anticoagulation therapy and age. The majority (88.6%) of bleeding events resolved or improved, 10.2% persisted and 1.3% led to death; 10.2% of bleeding events required bevacizumab interruption or discontinuation. This analysis from the SAiL trial reaffirms a comparable incidence of clinically significant bleeding associated with first-line bevacizumab and chemotherapy as previous phase III studies in NSCLC patients despite less stringent first-line selection criteria. Grade ≥ 3 bleeding appears to be comparable when analyzed for patient and tumor characteristics, including tumor cavitation and concomitant anticoagulation therapy. Most bleeding events resolved or improved, and interruption/discontinuation of bevacizumab was infrequent in a standard oncology practice setting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Phase I and pharmacokinetic study of combined treatment with perifosine and radiation in patients with advanced solid tumours

    International Nuclear Information System (INIS)

    Vink, Stefan R.; Schellens, Jan H.M.; Beijnen, Jos H.; Sindermann, Herbert; Engel, Juergen; Dubbelman, Ria; Moppi, Gemi; Hillebrand, Michel J.X.; Bartelink, Harry; Verheij, Marcel

    2006-01-01

    Purpose: Perifosine is an orally applicable, membrane-targeted alkylphosphocholine analogue with antitumour activity and radiosensitising properties in preclinical models. The purpose of this phase I study was to determine the feasibility and tolerability of concurrent daily perifosine and radiation in patients with advanced cancer. Patients and methods: Starting dose of perifosine was 50 mg/day; dose escalation was in steps of 50 mg. Daily administration commenced 2 days before radiotherapy and was continued throughout the radiation treatment. At least three patients were entered at each dose level; at the 150 mg/day level 10 patients were included. Pharmacokinetic sampling was performed weekly pre-dosing. Twenty-one patients were entered. Tumour types included NSCLC (n = 17), prostate, oesophageal, colon and bladder cancer. Most patients (16/21) had received prior chemotherapy; none radiotherapy. Median number of daily perifosine administrations was 31 (range 24-53). Mean radiation dose (BED 1 ) was 59.8 Gy (range 50.7-87.5 Gy in 13-28 fractions). Results: Major drug-related toxicities according to CTC criteria were nausea in 57%, fatigue in 48%, vomiting in 38%, diarrhoea in 38% and anorexia in 19%. No bone marrow toxicity was observed. DLT (nausea/vomiting) was encountered in two of five patients at the 200 mg/day dose level. Dose-dependent steady-state plasma levels were reached after 1 week. Major radiotherapy-related acute toxicity consisted of dysphagia in 38% and pneumonitis in 29%. Conclusion: Perifosine can be safely combined with fractionated radiotherapy. A dosage of 150 mg/day, to be started at least 1 week prior to radiotherapy, is recommended for phase II evaluation

  14. Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.

    Directory of Open Access Journals (Sweden)

    Takeshi Ishikawa

    Full Text Available BACKGROUND: Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT and that fibronectin CH296 (FN-CH296 together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer. METHODS: Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up. RESULTS: Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%. CONCLUSIONS: The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies. TRIAL REGISTRATION: UMIN UMIN000001835.

  15. Advanced functional materials in solid phase extraction for ICP-MS determination of trace elements and their species - A review.

    Science.gov (United States)

    He, Man; Huang, Lijin; Zhao, Bingshan; Chen, Beibei; Hu, Bin

    2017-06-22

    For the determination of trace elements and their species in various real samples by inductively coupled plasma mass spectrometry (ICP-MS), solid phase extraction (SPE) is a commonly used sample pretreatment technique to remove complex matrix, pre-concentrate target analytes and make the samples suitable for subsequent sample introduction and measurements. The sensitivity, selectivity/anti-interference ability, sample throughput and application potential of the methodology of SPE-ICP-MS are greatly dependent on SPE adsorbents. This article presents a general overview of the use of advanced functional materials (AFMs) in SPE for ICP-MS determination of trace elements and their species in the past decade. Herein the AFMs refer to the materials featuring with high adsorption capacity, good selectivity, fast adsorption/desorption dynamics and satisfying special requirements in real sample analysis, including nanometer-sized materials, porous materials, ion imprinting polymers, restricted access materials and magnetic materials. Carbon/silica/metal/metal oxide nanometer-sized adsorbents with high surface area and plenty of adsorption sites exhibit high adsorption capacity, and porous adsorbents would provide more adsorption sites and faster adsorption dynamics. The selectivity of the materials for target elements/species can be improved by using physical/chemical modification, ion imprinting and restricted accessed technique. Magnetic adsorbents in conventional batch operation offer unique magnetic response and high surface area-volume ratio which provide a very easy phase separation, greater extraction capacity and efficiency over conventional adsorbents, and chip-based magnetic SPE provides a versatile platform for special requirement (e.g. cell analysis). The performance of these adsorbents for the determination of trace elements and their species in different matrices by ICP-MS is discussed in detail, along with perspectives and possible challenges in the future

  16. Deletion in HSP110 T17: correlation with wild-type HSP110 expression and prognostic significance in microsatellite-unstable advanced gastric cancers.

    Science.gov (United States)

    Kim, Kyung-Ju; Lee, Tae Hun; Kim, Jung Ho; Cho, Nam-Yun; Kim, Woo Ho; Kang, Gyeong Hoon

    2017-09-01

    Deletion of the HSP110 T 17 mononucleotide repeat has recently been identified as a prognostic marker that is correlated with wild-type HSP110 (HSP110wt) expression in microsatellite instability-high (MSI-H) colorectal cancers. The aim of this study was to assess the correlation between deletion of the HSP110 T 17 repeat and expression of HSP110wt using DNA testing and immunohistochemistry and to determine the prognostic implications of HSP110 T 17 deletion in MSI-H advanced gastric cancers (GCs). The status of HSP110wt expression was evaluated by immunohistochemistry using an HSP110wt-specific antibody in 142 MSI-H advanced GCs. The size of the HSP110 T 17 repeat deletion was analyzed in 96 MSI-H advanced GCs; deletions were divided into small (0-2base pairs) and large deletions (3-5base pairs). Low and high expressions of HSP110wt were detected in 38 (26.8%) and 104 (73.2%) of the 142 cases, respectively. The HSP110 T 17 deletion was observed in 45 (46.9%) of the 96 MSI-H GC samples. Tumors with high expression of HSP110wt showed a tendency to have small or no deletion of HSP110 T 17 . In Kaplan-Meier survival analysis, tumors with a large HSP110 T 17 deletion were associated with favorable overall survival and disease-free survival compared with those with small/no deletion of HSP110 T 17 . However, HSP110 T 17 deletion size was not an independent prognostic factor in multivariate analysis. In summary, deletion of the HSP110 T 17 repeat was frequently observed in MSI-H GCs, and HSP110 T 17 deletion size was inversely correlated with HSP110wt expression status. Large HSP110 T 17 was not a prognostic indicator in MSI-H GCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Needs of people with advanced dementia in their final phase of life: A multi-perspective qualitative study in nursing homes.

    Science.gov (United States)

    Schmidt, Holger; Eisenmann, Yvonne; Golla, Heidrun; Voltz, Raymond; Perrar, Klaus Maria

    2018-03-01

    People with advanced dementia present an important target group for palliative care. They suffer a range of symptoms, and their verbal communication abilities are highly restricted. At present, little is known about their needs in the final phase of life. To identify the needs of people with advanced dementia in their final phase of life and to explore the aspects relevant to first recognize and then meet these needs. Multi-perspective qualitative study using grounded theory methodology conducting group discussions, individual interviews, and participant observation. The study encompassed nursing homes and involved health professionals, relatives, and residents with advanced dementia. Data were collected in six nursing homes. Nine group discussions and three individual interviews were conducted comprising 42 health professionals and 14 relatives. Participant observations aided in giving the perspective of 30 residents with advanced dementia. Data analysis generated a total of 25 physical, psychosocial, and spiritual needs divided into 10 categories. Physical needs were classified as follows: "food intake," "physical well-being," and "physical activity and recovery." Categories of psychosocial needs were classified as follows: "adaptation of stimuli," "communication," "personal attention," "participation," "familiarity and safety," as well as "self-determination." Spiritual needs addressed "religion." The results revealed a multitude of key aspects for recognizing and meeting these needs, stressing the importance of personhood. People with advanced dementia in their final phase of life have a multitude of individual and complex needs. This evidence contributes to narrowing the current research gap, offering an orientation framework for research and practice.

  18. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy

    DEFF Research Database (Denmark)

    Bellmunt, Joaquim; von der Maase, Hans; Mead, Graham M

    2012-01-01

    The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival....

  19. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik V; Jensen, Lars Henrik; Sorensen, Morten

    2011-01-01

    (O) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC). Methods. In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours...... and no other treatments or advanced CC. In the Phase II part response rate, toxicity, progression-free survival (PFS) and overall survival was evaluated in patients with newly diagnosed advanced CC. Results. Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1 and 15, O 60 mg/m(2) day 1...... and 15, and C 1 000 mg/m(2) BID day 1-7 and day 15-21 were established as MTD. In the Phase II part, 41 patients with advanced CC were included. Overall response rate was 34% and 51% had stable disease, resulting in a clinical benefit rate of 85%. Grade III and IV adverse events were rare. Median...

  20. First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Abdul Razak, Albiruni R; Mau-Sørensen, Morten; Gabrail, Nashat Y

    2016-01-01

    PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. PATIENTS AND METHODS: In total, 189 patients with advanced solid tumors...

  1. A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial

    NARCIS (Netherlands)

    Bui-Nguyen, B.; Butrynski, J.E.; Penel, N.; Blay, J.Y.; Isambert, N.; Milhem, M.; Kerst, J.M.; Reyners, A.K.; Litiere, S.; Marreaud, S.; Collin, F.; Graaf, W.T.A. van der

    2015-01-01

    PURPOSE: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour

  2. A phase I, dose-escalation study of TB-403, a monoclonal antibody directed against PlGF, in patients with advanced solid tumours

    DEFF Research Database (Denmark)

    Lassen, U; Nielsen, D L; Sørensen, M

    2012-01-01

    BACKGROUND: TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid...

  3. A phase I monotherapy study of RG7212, a first-in-class monoclonal antibody targeting TWEAK signaling in patients with advanced cancers

    DEFF Research Database (Denmark)

    Lassen, Ulrik N; Meulendijks, Didier; Siu, Lilian L

    2015-01-01

    activation. A phase I study of RG7212, a humanized anti-TWEAK IgG1κ monoclonal antibody, was conducted in patients with advanced solid tumors expressing Fn14. EXPERIMENTAL DESIGN: Dose escalations, over a 200- to 7,200-mg range, were performed with patients enrolled in weekly (QW), bi-weekly (Q2W), or every...

  4. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer

    DEFF Research Database (Denmark)

    Schlumberger, Martin J; Elisei, Rossella; Bastholt, Lars

    2009-01-01

    PURPOSE: This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC). PATIENTS A...

  5. Performance evaluation of a full-scale advanced phase isolation ditch process by using real-time control strategies

    International Nuclear Information System (INIS)

    Kim, Hyosoo; Kim, Yejin; Kim, Minsoo; Piao, Wenhua; Kim, Changwon; Gee, Jeasung

    2014-01-01

    This paper proposes real-time control strategies that can be applied in a full-scale advanced phase isolation ditch (APID) process. Real-time operation mode control (OMC) and aeration section control (ASC) strategies were developed to cope more stably with fluctuations in the influent loading and to increase the nitrification and denitrification reactions within the entire volume. The real-time OMC and ASC strategies were evaluated using mathematical models. When the NH 4 -N in the reactor was maintained at a high level, appropriate control actions, such as continuing the aeration state, stopping the influent inflow and increasing the aeration section, were applied in the APID process. In contrast, when the NO X -N in the reactor was maintained at a high level, the non-aeration state, influent inflow, and decreased aeration section were continued. It was concluded that stable operation in the APID process could be achieved by applying real-time OMC and ASC strategies developed in this study

  6. Performance evaluation of a full-scale advanced phase isolation ditch process by using real-time control strategies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyosoo; Kim, Yejin; Kim, Minsoo; Piao, Wenhua; Kim, Changwon [Pusan National University, Busan (Korea, Republic of); Gee, Jeasung [Taiwha Industrial Co. Ltd., Seoul (Korea, Republic of)

    2014-04-15

    This paper proposes real-time control strategies that can be applied in a full-scale advanced phase isolation ditch (APID) process. Real-time operation mode control (OMC) and aeration section control (ASC) strategies were developed to cope more stably with fluctuations in the influent loading and to increase the nitrification and denitrification reactions within the entire volume. The real-time OMC and ASC strategies were evaluated using mathematical models. When the NH{sub 4}-N in the reactor was maintained at a high level, appropriate control actions, such as continuing the aeration state, stopping the influent inflow and increasing the aeration section, were applied in the APID process. In contrast, when the NO{sub X}-N in the reactor was maintained at a high level, the non-aeration state, influent inflow, and decreased aeration section were continued. It was concluded that stable operation in the APID process could be achieved by applying real-time OMC and ASC strategies developed in this study.

  7. Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Morak, Marjolein J.M.; Richel, Dick J.; Eijck, Casper H.J. van; Nuyttens, Joost J.M.E.; Gaast, Ate van der; Vervenne, Walter L.; Padmos, Esther E.; Schaake, Eva E.; Busch, Olivier R.C.; Tienhoven, Geertjan van

    2011-01-01

    Background and purpose: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer. Material and methods: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20 x 2.5 Gy radiotherapy combined with UFT 300 mg/m 2 per day, leucovorin (folinic acid) 30 mg and celecoxib 800 mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up. Results: Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths. Conclusions: Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment.

  8. Phase I safety, pharmacokinetic and pharmacodynamic evaluation of the vascular disrupting agent ombrabulin (AVE8062) in patients with advanced solid tumors.

    Science.gov (United States)

    Sessa, Cristiana; Lorusso, Patricia; Tolcher, Anthony; Farace, Françoise; Lassau, Nathalie; Delmonte, Angelo; Braghetti, Antonio; Bahleda, Rastislav; Cohen, Patrick; Hospitel, Marie; Veyrat-Follet, Christine; Soria, Jean-Charles

    2013-09-01

    The vascular disrupting agent ombrabulin rapidly reduces tumor blood flow and causes necrosis in vivo. A phase I dose-escalation study was designed to determine the recommended phase II dose (RP2D) of single-agent ombrabulin administered once every three weeks in patients with advanced solid malignancies. Ombrabulin (30-minute infusion) was escalated from 6 to 60 mg/m2, with RP2D cohort expansion. Safety, tumor response, pharmacokinetics, and pharmacodynamic biomarkers were evaluated. Eleven dose levels were evaluated in 105 patients. Two patients had dose-limiting toxicities in cycle 1 during escalation: grade 3 abdominal pain at 50 mg/m2, grade 3 tumor pain/grade 3 hypertension at 60 mg/m2, and the RP2D was 50 mg/m2 (39 patients). Common toxicities were headache, asthenia, abdominal pain, nausea, diarrhea, transient hypertension, anemia, and lymphopenia. No clinically significant QTc prolongations or left ventricular ejection fraction (LVEF) decreases occurred. Ombrabulin was rapidly converted to its active metabolite RPR258063 (half-life 17 minutes and 8.7 hours, respectively), both having dose-proportional exposure. Weak inhibition of CYP2C19-mediated metabolism occurred at the clinical doses used and there was no effect on CYP1A2 and CYP3A4. A patient with rectal cancer had a partial response and eight patients had stable disease lasting four months or more. Circulating endothelial cells (CEC), VEGF, and matrix metalloproteinase (MMP)-9 levels increased significantly six to 10 hours postinfusion in a subset of patients. The recommended schedule for single-agent ombrabulin is 50 mg/m2 every 3 weeks. CECs, VEGF, and MMP-9 are potential biomarkers of ombrabulin activity. ©2013 AACR.

  9. Complications of hyperglycaemia with PI3K–AKT–mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials

    Science.gov (United States)

    Geuna, E; Roda, D; Rafii, S; Jimenez, B; Capelan, M; Rihawi, K; Montemurro, F; Yap, T A; Kaye, S B; De Bono, J S; Molife, L R; Banerji, U

    2015-01-01

    Background: PI3K–AKT–mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients. Methods: Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups. Results: The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3–4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3–4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. Conclusions: PI3K–AKT–mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers. PMID:26554652

  10. Concurrent chemoradiotherapy in locally advanced carcinoma of the uterine cervix: a phase I/II prospective study

    International Nuclear Information System (INIS)

    Kang, One Chul; Choi, Eun Kyung; Chung, Weon Kuu; Kim, Jong Hoon; Chang, Hye Sook; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun; Mok, Jung Eun; Lee, Moo Song

    1998-01-01

    Prospective, single arm. Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. From May 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The international Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4, 140-5, 040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/m 2 /day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/m 2 /dy intravenous bolus for 3 days, day 1-3, 29-31) administered starting on day 1 of 1 of RT. The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52% and 64%, respectively. The 5-year actuarial survival for stage IIB and II+IVA patients were 58% and 36%, respectively. The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71% and 46%, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9% (19/68): local failure in 5.9% (4/68), distant metastasis in 10.3% (7/68) and both in 11.8% (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment, the complete response rate was 78% (50/64). Concurrent chemoradiation appear to be a

  11. Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

    International Nuclear Information System (INIS)

    Chitapanarux, Imjai; Kamnerdsupaphon, Pimkhuan; Pukanhapan, Nantaka; Tharavichitkul, Ekkasit; Vongtama, Roy

    2013-01-01

    The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III-IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3-102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3 - 4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer. (author)

  12. Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI.

    Science.gov (United States)

    Kim, Eun Young; Kim, Nambeom; Kim, Young Saing; Seo, Ja-Young; Park, Inkeun; Ahn, Hee Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable. Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p ALI using BMI. ALI is a simple and useful prognostic indicator in SCLC.

  13. Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study

    International Nuclear Information System (INIS)

    Spanos, W.J. Jr.; Wasserman, T.; Meoz, R.; Sala, J.; Kong, J.; Stetz, J.

    1987-01-01

    Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses

  14. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer.

    Science.gov (United States)

    Cohen, Ezra E W; Karrison, Theodore G; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H; Brockstein, Bruce E; Agulnik, Mark B; Mittal, Bharat B; Yunus, Furhan; Samant, Sandeep; Raez, Luis E; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y; Villaflor, Victoria M; Haraf, Daniel J; Vokes, Everett E

    2014-09-01

    Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. © 2014 by American Society of Clinical Oncology.

  15. Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

    Science.gov (United States)

    Cohen, Ezra E.W.; Karrison, Theodore G.; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H.; Brockstein, Bruce E.; Agulnik, Mark B.; Mittal, Bharat B.; Yunus, Furhan; Samant, Sandeep; Raez, Luis E.; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y.; Villaflor, Victoria M.; Haraf, Daniel J.; Vokes, Everett E.

    2014-01-01

    Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. PMID:25049329

  16. Radiotherapy versus concurrent 5-day cisplatin and radiotherapy in locally advanced cervical carcinoma. Long-term results of a Phase III randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Viorica; Coza, Ovidiu; Ghilezan, Nicolae [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Radiation Oncology; ' Iuliu Hatieganu' Univ. of Medicine and Pharmacy, Cluj-Napoca (Romania); Ordeanu, Claudia; Todor, Nicolae [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Radiation Oncology; Traila, Alexandru [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Surgery; Rancea, Alin [' Iuliu Hatieganu' Univ. of Medicine and Pharmacy, Cluj-Napoca (Romania); ' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Surgery

    2009-03-15

    Purpose: To prove the superiority of concurrent radiochemotherapy (RTCT) over radiotherapy (RT) alone in locally advanced cervical carcinoma. Patients and Methods: In this randomized monocentric phase III study, 566 patients with squamous cell carcinoma of the cervix were included: 284 in arm A (RT) and 282 in arm B (concurrent RTCT with cisplatin 20 mg/m{sup 2} x 5 days). 238 patients (42%) were in stage IIB, 209 (37%) in stage IIIA, and 119 (21%) in stage IIIB. The median follow-up was 62.8 months. RT to the pelvis was delivered to a dose of 46 Gy/23 fractions. A cervical boost was given using the X-ray arch technique or high-dose-rate intracavitary brachytherapy at a dose of 10 Gy. Thereafter, patients were evaluated: those with good response optionally underwent surgery and the others continued RT until 64 Gy/pelvis (with or without CT according to randomization) and 14 Gy/central tumor volume. Results: The 5-year survival rate was statistically significantly superior in the concurrent RTCT group (74%) versus the RT group (64%; p < 0.05). In patients undergoing surgery after RT or RTCT, superior results were obtained, compared to the nonoperated patients: 5-year survival rate 86% versus 53% (p < 0.01). 192 failures were recorded: 109 (38%) after RT alone versus 83 (29%) after concurrent RTCT (p < 0.01). Conclusion: The results of this study prove the obvious superiority of concurrent RTCT with 5-day cisplatin compared to RT alone in patients with locally advanced cervical carcinoma, regarding local control (78% vs. 67%) and 5-year survival rates (74% vs. 64%). (orig.)

  17. Advanced analytical method of nereistoxin using mixed-mode cationic exchange solid-phase extraction and GC/MS.

    Science.gov (United States)

    Park, Yujin; Choe, Sanggil; Lee, Heesang; Jo, Jiyeong; Park, Yonghoon; Kim, Eunmi; Pyo, Jaesung; Jung, Jee H

    2015-07-01

    Nereistoxin(NTX) was originated from a marine annelid worm Lumbriconereis heteropoda and its analogue pesticides including cartap, bensultap, thiocyclam and thiobensultap have been commonly used in agriculture, because of their low toxicity and high insecticidal activity. However, NTX has been reported about its inhibitory neuro toxicity in human and animal body, by blocking nicotinic acetylcholine receptor and it cause significant neuromuscular toxicity, resulting in respiratory failure. We developed a new method to determine NTX in biological fluid. The method involves mixed-mode cationic exchange based solid phase extraction and gas chromatography/mass spectrometry for final identification and quantitative analysis. The limit of detection and recovery were substantially better than those of other methods using liquid-liquid extraction or headspace solid phase microextraction. The good recoveries (97±14%) in blood samples were obtained and calibration curves over the range 0.05-20 mg/L have R2 values greater than 0.99. The developed method was applied to a fatal case of cartap intoxication of 74 years old woman who ingested cartap hydrochloride for suicide. Cartap and NTX were detected from postmortem specimens and the cause of the death was ruled to be nereistoxin intoxication. The concentrations of NTX were 2.58 mg/L, 3.36 mg/L and 1479.7 mg/L in heart, femoral blood and stomach liquid content, respectively. The heart blood/femoral blood ratio of NTX was 0.76. Copyright © 2015. Published by Elsevier Ireland Ltd.

  18. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Valente Nancy

    2005-02-01

    Full Text Available Abstract Background There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC-derived exosomes (DEX loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC. Methods This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4 and IV (N = 9 NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Results Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8, flu like illness (N = 1, and peripheral arm pain (N = 1. The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Conclusion Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors

  19. NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Patrick J. Mansky

    2013-01-01

    Full Text Available Purpose. European Mistletoe (Viscum album L. extracts (mistletoe are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM and mistletoe in advanced solid cancers (ASC evaluated: (1 safety, toxicity, and maximum tolerated dose (MTD, (2 absolute neutrophil count (ANC recovery, (3 formation of mistletoe lectin antibodies (ML ab, (4 cytokine plasma concentrations, (5 clinical response, and (6 pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT were grade (G 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

  20. SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma.

    Science.gov (United States)

    Schuetze, Scott M; Wathen, J Kyle; Lucas, David R; Choy, Edwin; Samuels, Brian L; Staddon, Arthur P; Ganjoo, Kristen N; von Mehren, Margaret; Chow, Warren A; Loeb, David M; Tawbi, Hussein A; Rushing, Daniel A; Patel, Shreyaskumar R; Thomas, Dafydd G; Chugh, Rashmi; Reinke, Denise K; Baker, Laurence H

    2016-03-15

    Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma. Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients. Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity. © 2015 American Cancer Society.

  1. Phase II study of capecitabine (Xeloda (registered) ) and concomitant boost radiotherapy in patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Krishnan, Sunil; Janjan, Nora A.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Wolff, Robert A.; Das, Prajnan; Delclos, Marc E.; Chang, George J.; Hoff, Paulo M.; Eng, Cathy; Brown, Thomas D.; Crane, Christopher H.; Feig, Barry W.; Morris, Jeffrey; Vadhan-Raj, Saroj; Hamilton, Stanley R.; Lin, Edward H.

    2006-01-01

    Purpose: The aim of this study was to determine the efficacy of capecitabine (Xeloda (registered) ), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC). Methods and Materials: We conducted a phase II study of capecitabine (825 mg/m 2 orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative ≥T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was pathologic response rate; secondary endpoints included toxicity profiles and survival parameters. Results: Of the 54 patients (median age, 56.7 years; range, 21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS. Surgery was not performed in 3 patients; 2 of these patients had metastatic disease, and the third patient refused after a complete clinical response. Of the 51 patients evaluable for pathologic response, 9 patients (18%) achieved complete response, and 12 patients (24%) had microscopic residual disease (<10% viable cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging, and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for tumor ≤5 cm from the anal verge was 67% (18/27). Conclusion: This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU. The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC

  2. Phase I dose escalation study of KOS-1584, a novel epothilone, in patients with advanced solid tumors.

    Science.gov (United States)

    Lam, Elaine T; Goel, Sanjay; Schaaf, Larry J; Cropp, Gillian F; Hannah, Alison L; Zhou, Yiqing; McCracken, Barbara; Haley, Brandi I; Johnson, Robert G; Mani, Sridhar; Villalona-Calero, Miguel A

    2012-02-01

    First-in-man study of KOS-1584, a second generation epothilone. Patients with advanced solid malignancies received KOS-1584 every 3 weeks until disease progression. Using a modified Fibonacci dose escalation scheme, one patient was enrolled at each dose level until the first instance of grade 2 toxicity. Thereafter, a standard 3 + 3 design was utilized. Sixty-six patients in 14 cohorts were dosed from 0.8 to 48 mg/m(2). Diarrhea, arthralgias, and encephalopathy were dose-limiting toxicities (DLTs) at doses ≥36 mg/m(2). At the recommended phase II dose (RP2D), the most common adverse effects were peripheral neuropathy (low grade), fatigue, arthralgias/myalgias, and diarrhea (31, 6%). The incidence of neutropenia was low. The overall clearance, volume of distribution, and half-life of KOS-1584 were 11 ± 6.17 L/h/m(2), 327 ± 161 L/m(2), and 21.9 ± 8.75 h, respectively. The half-life for the seco-metabolite (KOS-1891) was 29.6 ± 13.8 h. KOS-1584 exhibited linear pharmacokinetics. A dose-dependent increase in microtubulin bundle formation was observed at doses ≥27 mg/m(2). Two patients achieved partial responses and 24 patients had stable disease (SD). The RP2D of KOS-1584 is 36 mg/m(2). The lack of severe neurologic toxicity, diarrhea, neutropenia, or hypersensitivity reactions; favorable pharmacokinetic profile; and early evidence of activity support further evaluation.

  3. Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial.

    Science.gov (United States)

    Bines, J; Dienstmann, R; Obadia, R M; Branco, L G P; Quintella, D C; Castro, T M; Camacho, P G; Soares, F A; Costa, M E F

    2014-04-01

    As novel treatments carry substantial price tags and are mostly cost-prohibitive in low- and middle-income countries, there is an urgent need to develop alternatives, such as off-patent drugs. Megestrol acetate (MA) has a longstanding history in the treatment of breast cancer, but recently it is being used less often due to the advent of newer agents. This two-stage phase II trial evaluated the antitumor activity and toxicity of MA in postmenopausal women with hormone-sensitive advanced breast cancer who had experienced disease progression on a third-generation nonsteroidal aromatase inhibitor (NSAI). Eligible patients had metastatic breast cancer treated with a NSAI with at least 6-month progression-free survival (PFS), or relapse after ≥1 year on adjuvant NSAI. Patients received MA at a single daily oral dose of 160 mg. Primary end point was clinical benefit rate (CBR). Forty-eight patients were enrolled. The CBR was 40% [95% confidence interval (CI) 25% to 55%], and the median duration of clinical benefit was 10.0 (95% CI 8.0-14.2) months. The median PFS was 3.9 (95% CI 3.0-4.8) months. The most common grade 3 adverse events were anemia (2%), dyspnea (2%), fatigue (2%), musculoskeletal pain (4%), deep vein thrombosis (10%), and weight gain (2%). This is the first study to prospectively evaluate the efficacy and safety of MA in postmenopausal women with hormone-sensitive disease progressing on a NSAI. MA has demonstrated activity and acceptable tolerability in this setting, and therefore remains a reasonable treatment option in a cost-sensitive environment. These results also provide the background for further evaluation of progestins in the treatment of breast cancer. local trial number, related to the approval by the IRB: CEP 108/06.

  4. A phase I open-label trial evaluating the cardiovascular safety of regorafenib in patients with advanced cancer.

    Science.gov (United States)

    Jones, Robin L; Bendell, Johanna C; Smith, David C; Diefenbach, Konstanze; Lettieri, John; Boix, Oliver; Lockhart, A Craig; O'Bryant, Cindy; Moore, Kathleen N

    2015-10-01

    To characterize the cardiovascular safety profile of regorafenib in patients with advanced cancer. Patients received regorafenib 160 mg/day for 21 days followed by a 7-day break. The primary endpoint was the change from baseline in QTcF at the regorafenib t(max) (Day 21, Cycle 1 or 2) and changes in left ventricular ejection fraction (LVEF) from baseline on Cycle 2, Day 21. Secondary objectives were pharmacokinetics, safety, anti-tumor activity and effects on electrocardiogram intervals. QT intervals were corrected using the methods of Fridericia (QTcF) and Bazett (QTcB). LVEF was assessed by multigated acquisition scanning. Fifty-three patients were enrolled, and all received at least one dose of regorafenib 160 mg. Twenty-five patients received regorafenib for 21 days without dose reduction. The mean change from baseline in QTcF at t(max) was (-)2 ms (90 % CI -8, 3). No patient experienced a change from baseline in QTcF > 60 ms, and two had QTcF changes between 30 and 60 ms. No patient had a QTcF or QTcB > 480 ms. In 27 patients who received at least 80 mg of regorafenib, the mean change from baseline in LVEF% ± SD was 1.7 ± 7.8. In 14 patients without a dose reduction, the mean change from baseline in LVEF% was (-)0.1 ± 8.6 at Cycle 2, Day 21. Four patients experienced a LVEF decrease between 10 and 20 %. The effects of regorafenib on the QT/QTc interval and LVEF were modest and unlikely to be of clinical significance in the setting of advanced cancer therapy.

  5. Subgroup analysis of East Asians in RAINBOW: A phase 3 trial of ramucirumab plus paclitaxel for advanced gastric cancer.

    Science.gov (United States)

    Muro, Kei; Oh, Sang Cheul; Shimada, Yasuhiro; Lee, Keun-Wook; Yen, Chia-Jui; Chao, Yee; Cho, Jae Yong; Cheng, Rebecca; Carlesi, Roberto; Chandrawansa, Kumari; Orlando, Mauro; Ohtsu, Atsushi

    2016-03-01

    East Asia has higher gastric cancer incidence and mortality rates than other regions. We present a subgroup analysis of East Asians in the positive study RAINBOW. Patients with advanced gastric or gastroesophageal junction adenocarcinoma previously treated with platinum and fluoropyrimidine received ramucirumab 8 mg/kg or placebo on days 1 and 15 plus paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Of 665 intention-to-treat patients, 223 were East Asian. Median overall survival was 12.1 months for ramucirumab plus paclitaxel and 10.5 months for placebo plus paclitaxel (hazard ratio: 0.986, 95% confidence interval: 0.727-1.337, P = 0.929). Median progression-free survival was 5.5 months for ramucirumab plus paclitaxel and 2.8 months for placebo plus paclitaxel (hazard ratio: 0.628, 95% confidence interval: 0.473-0.834, P = 0.001). Objective response rates were 34% for ramucirumab plus paclitaxel and 20% for placebo plus paclitaxel. Grade ≥ 3 neutropenia (60% vs 28%) and leukopenia (34% vs 13%) were higher for ramucirumab plus paclitaxel. The rate of febrile neutropenia was low (4% vs 4%). Special interest adverse events included any grade bleeding/hemorrhage (55% vs 25%), proteinuria (27% vs 7%), and hypertension (22% vs 2%). Ramucirumab plus paclitaxel significantly improves progression-free survival and response rate, with prolonged median overall survival and an acceptable safety profile in East Asians with advanced gastric cancer. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors.

    Directory of Open Access Journals (Sweden)

    Ignacio Garrido-Laguna

    Full Text Available To evaluate clinicopathologic and molecular features of patients with metastatic colorectal cancer (mCRC and their outcomes in early-phase trials using pathway-targeting agents.We analyzed characteristics of 238 patients with mCRC referred to the phase 1 trials unit at MD Anderson Cancer Center. KRAS, PIK3CA and BRAF status were tested using PCR-based DNA sequencing.Fifty-one percent of patients harbored KRAS mutations; 15% had PIK3CA mutations. In the multivariate regression model for clinical characteristics KRAS mutations were associated with an increased incidence of lung and bone metastases and decreased incidence of adrenal metastases; PIK3CA mutations were marginally correlated with mucinous tumors (p = 0.05. In the univariate analysis, KRAS and PIK3CA mutations were strongly associated. Advanced Duke's stage (p<0.0001 and KRAS mutations (p = 0.01 were the only significant independent predictors of poor survival (Cox proportional hazards model. Patients with PIK3CA mutations had a trend toward shorter progression-free survival when treated with anti-EGFR therapies (p = 0.07. Eighteen of 78 assessable patients (23% treated with PI3K/Akt/mTOR axis inhibitors achieved stable disease [SD] ≥6 months or complete response/partial response (CR/PR, only one of whom were in the subgroup (N = 15 with PIK3CA mutations, perhaps because 10 of these 15 patients (67% had coexisting KRAS mutations. No SD ≥6 months/CR/PR was observed in the 10 patients treated with mitogen-activating protein kinase (MAPK pathway targeting drugs.KRAS and PIK3CA mutations frequently coexist in patients with colorectal cancer, and are associated with clinical characteristics and outcome. Overcoming resistance may require targeting both pathways.

  7. A Phase I/Ib Study of Enzalutamide Alone and in Combination with Endocrine Therapies in Women with Advanced Breast Cancer.

    Science.gov (United States)

    Schwartzberg, Lee S; Yardley, Denise A; Elias, Anthony D; Patel, Manish; LoRusso, Patricia; Burris, Howard A; Gucalp, Ayca; Peterson, Amy C; Blaney, Martha E; Steinberg, Joyce L; Gibbons, Jacqueline A; Traina, Tiffany A

    2017-08-01

    Purpose: Several lines of evidence support targeting the androgen signaling pathway in breast cancer. Enzalutamide is a potent inhibitor of androgen receptor signaling. Preclinical data in estrogen-expressing breast cancer models demonstrated activity of enzalutamide monotherapy and enhanced activity when combined with various endocrine therapies (ET). Enzalutamide is a strong cytochrome P450 3A4 (CYP3A4) inducer, and ETs are commonly metabolized by CYP3A4. The pharmacokinetic (PK) interactions, safety, and tolerability of enzalutamide monotherapy and in combination with ETs were assessed in this phase I/Ib study. Experimental Design: Enzalutamide monotherapy was assessed in dose-escalation and dose-expansion cohorts of patients with advanced breast cancer. Additional cohorts examined effects of enzalutamide on anastrozole, exemestane, and fulvestrant PK in patients with estrogen receptor-positive/progesterone receptor-positive (ER + /PgR + ) breast cancer. Results: Enzalutamide monotherapy ( n = 29) or in combination with ETs ( n = 70) was generally well tolerated. Enzalutamide PK in women was similar to prior data on PK in men with prostate cancer. Enzalutamide decreased plasma exposure to anastrozole by approximately 90% and exemestane by approximately 50%. Enzalutamide did not significantly affect fulvestrant PK. Exposure of exemestane 50 mg/day given with enzalutamide was similar to exemestane 25 mg/day alone. Conclusions: These results support a 160 mg/day enzalutamide dose in women with breast cancer. Enzalutamide can be given in combination with fulvestrant without dose modifications. Exemestane should be doubled from 25 mg/day to 50 mg/day when given in combination with enzalutamide; this combination is being investigated in a randomized phase II study in patients with ER + /PgR + breast cancer. Clin Cancer Res; 23(15); 4046-54. ©2017 AACR . ©2017 American Association for Cancer Research.

  8. EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer.

    Science.gov (United States)

    Yardley, Denise A; Weaver, Robert; Melisko, Michelle E; Saleh, Mansoor N; Arena, Francis P; Forero, Andres; Cigler, Tessa; Stopeck, Alison; Citrin, Dennis; Oliff, Ira; Bechhold, Rebecca; Loutfi, Randa; Garcia, Agustin A; Cruickshank, Scott; Crowley, Elizabeth; Green, Jennifer; Hawthorne, Thomas; Yellin, Michael J; Davis, Thomas A; Vahdat, Linda T

    2015-05-10

    Glycoprotein NMB (gpNMB), a negative prognostic marker, is overexpressed in multiple tumor types. Glembatumumab vedotin is a gpNMB-specific monoclonal antibody conjugated to the potent cytotoxin monomethyl auristatin E. This phase II study investigated the activity of glembatumumab vedotin in advanced breast cancer by gpNMB expression. Patients (n = 124) with refractory breast cancer that expressed gpNMB in ≥ 5% of epithelial or stromal cells by central immunohistochemistry were stratified by gpNMB expression (tumor, low stromal intensity, high stromal intensity) and were randomly assigned 2:1 to glembatumumab vedotin (n = 83) or investigator's choice (IC) chemotherapy (n = 41). The study was powered to detect overall objective response rate (ORR) in the glembatumumab vedotin arm between 10% (null) and 22.5% (alternative hypothesis) with preplanned investigation of activity by gpNMB distribution and/or intensity (Stratum 1 to Stratum 3). Glembatumumab vedotin was well tolerated as compared with IC chemotherapy (less hematologic toxicity; more rash, pruritus, neuropathy, and alopecia). ORR was 6% (five of 83) for glembatumumab vedotin versus 7% (three of 41) for IC, without significant intertreatment differences for predefined strata. Secondary end point revealed ORR of 12% (10 of 83) versus 12% (five of 41) overall, and 30% (seven of 23) versus 9% (one of 11) for gpNMB overexpression (≥ 25% of tumor cells). Unplanned analysis showed ORR of 18% (five of 28) versus 0% (0 of 11) in patients with triple-negative breast cancer (TNBC), and 40% (four of 10) versus 0% (zero of six) in gpNMB-overexpressing TNBC. Glembatumumab vedotin is well tolerated in heavily pretreated patients with breast cancer. Although the primary end point in advanced gpNMB-expressing breast cancer was not met for all enrolled patients (median tumor gpNMB expression, 5%), activity may be enhanced in patients with gpNMB-overexpressing tumors and/or TNBC. A pivotal phase II trial (METRIC

  9. Study of Pu consumption in advanced light water reactors: Evaluation of GE advanced boiling water reactor plants - compilation of Phase 1B task reports

    International Nuclear Information System (INIS)

    1993-01-01

    This report contains an extensive evaluation of GE advanced boiling water reactor plants prepared for United State Department of Energy. The general areas covered in this report are: core and system performance; fuel cycle; infrastructure and deployment; and safety and environmental approval

  10. Study of Pu consumption in advanced light water reactors: Evaluation of GE advanced boiling water reactor plants - compilation of Phase 1B task reports

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-09-15

    This report contains an extensive evaluation of GE advanced boiling water reactor plants prepared for United State Department of Energy. The general areas covered in this report are: core and system performance; fuel cycle; infrastructure and deployment; and safety and environmental approval.

  11. U.S. Geological Survey assessment of global potash production and resources—A significant advancement for global development and a sustainable future.

    Science.gov (United States)

    Cocker, Mark D.; Orris, Greta J.; Wynn, Jeff

    2016-01-01

    During the past 15 yr, the global requirement for fertilizers has grown considerably, mainly due to demand by a larger and wealthier world population for more and higher-quality food. The demand and price for potash as a primary fertilizer ingredient have increased in tandem, because of the necessity to increase the quantity and quality of food production on the decreasing amount of available arable land. The primary sources of potash are evaporates, which occur mainly in marine salt basins and a few brine-bearing continental basins. World potash resources are large, but distribution is inequitable and not presently developed in countries where population and food requirements are large and increasing. There is no known substitute for potash in fertilizer, so knowledge of the world’s potash resources is critical for a sustainable future. The U.S. Geological Survey recently completed a global assessment of evaporite-hosted potash resources, which included a geographic information system–based inventory of known potash resources. This assessment included permissive areas or tracts for undiscovered resources at a scale of 1:1,000,000. Assessments of undiscovered potash resources were conducted for a number of the world’s evaporite-hosted potash basins. The data collected provide a major advance in our knowledge of global potash resources that did not exist prior to this study. The two databases include: (1) potash deposits and occurrences, and (2) potash tracts (basins that contain these deposits and occurrences and potentially undiscovered potash deposits). Data available include geology, mineralogy, grade, tonnage, depth, thickness, areal extent, and structure, as well as numerous pertinent references.

  12. Advanced Recombinant Manganese Peroxidase for Biosynthesis of Lignin Bioproducts, Phase I Final Report, STTR Grant #: DE-SC0007503.

    Energy Technology Data Exchange (ETDEWEB)

    Beatty, Christopher; Kitner, Joshua; Lajoie, Curtis; McClain, Sean; Potochnik, Steve

    2012-12-13

    The core purpose of this Phase I STTR was to evaluate the feasibility of a new method of producing a recombinant version of manganese peroxidase (MnP) enzyme. MnP is a potentially valuable enzyme for producing high value lignin products and also for industrial de-coloring operations such as biobleaching of pulp and color removal from textile dye effluents. This lignin-modifying enzyme is produced in small amounts by the native host, a white rot fungus. Previous work by Oregon State University developed a secreted recombinant version of the enzyme in the yeast Pichia pastoris. Unfortunately, the expression is barely moderate and the enzyme is heavily glycosylated, which inhibits purification. In this work, the gene for the enzyme is given a tag which targets production of the enzyme to the peroxisome. This is a promising approach since this location is also where heme and hydrogen peroxide are sequestered, which are both necessary cofactors for MnP. More than ten recombinant strains were constructed, verified, and expressed in the Pichia system. Constitutive (GAP) and methanol-induced promoters (AOX) were tried for peroxisomal targeted, cytosolic, and secreted versions of MnP. Only the secreted strains showed activity. The amount of expression was not significantly changed. The degree of glycosylation was lessened using the AOX (methanol) promotoer, but the resulting enzyme was still not able to be purified using immobilized metal affinity chromatography. Additional work beyond the scope of the defined Phase I project was undertaken to construct, verify, and express Pichia strains that mutated the MnP glycosylation sites to inhibit this process. These strains did not show significant activity. The cause is not known, but it is possible that these sites are important to the structure of the enzyme. Also beyond the scope proposed for our Phase I STTR, the team collaborated with AbSci, a startup with a new E. coli based expression system focused on the production of

  13. Phase I and II trial of five-day infused 5-fluorouracil and radiation in advanced cancer of the head and neck

    International Nuclear Information System (INIS)

    Byfield, J.E.; Sharp, T.R.; Frankel, S.S.; Tang, S.G.; Callipari, F.B.

    1984-01-01

    Eighteen patients with advanced epithelial cancers of the head and neck region were studied for their tolerance and response to combined cycles of 120-hour infused 5-fluorouracil (5-FU) and external-beam radiation therapy. 5-FU infusions were given under conditions where radiosensitization would be expected at the higher infusion doses. Coincident radiation treatments were given as four sequential daily fractions of 250 rad each administered during days 1 through 4 of each five-day infusion cycle. The patients were rested for at least nine days after each cycle or longer until toxicity was resolved. The regimen was then repeated in each patient for a total of five treatment cycles. Thereafter therapy was consolidated, usually by boost radiation without drug. In sequential patient subsets the infusion load was progressively escalated in a phase I format. The complete response rate for stage IV patients was 75% with survival benefit compared to prior results. 5-FU dose-dependent combined modality loco-regional toxicity was demonstrated without significant enhancement of systemic toxicity of any form; 5-FU dose-dependent enhanced responsiveness and survival benefit is also suggested. Further scheduling and response studies of 5-FU under radiosensitizing conditions appear warranted

  14. β-Phase poly(vinylidene fluoride) films encouraged more homogeneous cell distribution and more significant deposition of fibronectin towards the cell–material interface compared to α-phase poly(vinylidene fluoride) films

    Energy Technology Data Exchange (ETDEWEB)

    Low, Y.K.A.; Zou, X. [School of Materials Science and Engineering, Nanyang Technological University, N4.1 50 Nanyang Avenue, Singapore 639798 (Singapore); Fang, Y.M. [School of Computer Engineering, Nanyang Technological University, N4 50 Nanyang Avenue, Singapore 639798 (Singapore); Wang, J.L. [School of Materials Science and Engineering, Nanyang Technological University, N4.1 50 Nanyang Avenue, Singapore 639798 (Singapore); Lin, W.S. [School of Computer Engineering, Nanyang Technological University, N4 50 Nanyang Avenue, Singapore 639798 (Singapore); Boey, F.Y.C. [School of Materials Science and Engineering, Nanyang Technological University, N4.1 50 Nanyang Avenue, Singapore 639798 (Singapore); Ng, K.W., E-mail: kwng@ntu.edu.sg [School of Materials Science and Engineering, Nanyang Technological University, N4.1 50 Nanyang Avenue, Singapore 639798 (Singapore)

    2014-01-01

    The piezoelectric response from β-phase poly(vinylidene fluoride) (PVDF) can potentially be exploited for biomedical application. We hypothesized that α and β-phase PVDF exert direct but different influence on cellular behavior. α- and β-phase PVDF films were synthesized through solution casting and characterized with FT-IR, XRD, AFM and PFM to ensure successful fabrication of α and β-phase PVDF films. Cellular evaluation with L929 mouse fibroblasts over one-week was conducted with AlamarBlue® metabolic assay and PicoGreen® proliferation assay. Immunostaining of fibronectin investigated the extent and distribution of extracellular matrix deposition. Image saliency analysis quantified differences in cellular distribution on the PVDF films. Our results showed that β-phase PVDF films with the largest area expressing piezoelectric effect elicited highest cell metabolic activity at day 3 of culture. Increased fibronectin adsorption towards the cell–material interface was shown on β-phase PVDF films. Image saliency analysis showed that fibroblasts on β-phase PVDF films were more homogeneously distributed than on α-phase PVDF films. Taken collectively, the different molecular packing of α and β-phase PVDF resulted in differing physical properties of films, which in turn induced differences in cellular behaviors. Further analysis of how α and β-phase PVDF may evoke specific cellular behavior to suit particular application will be intriguing. - Highlights: • β-Phase PVDF exhibited strongest piezoelectric effects compared to α-phase PVDF. • β-Phase PVDF induced more homogeneous cell distribution than α-phase PVDF. • β-Phase PVDF encouraged more fibronectin deposition at the cell–material interface.

  15. Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518.

    Science.gov (United States)

    Yao, James C; Guthrie, Katherine A; Moran, Cesar; Strosberg, Jonathan R; Kulke, Matthew H; Chan, Jennifer A; LoConte, Noelle; McWilliams, Robert R; Wolin, Edward M; Mattar, Bassam; McDonough, Shannon; Chen, Helen; Blanke, Charles D; Hochster, Howard S

    2017-05-20

    Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.

  16. High Watts per Kilogram - Advanced Integration and Heat Management solar array technology (HaWK-AIHM ), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Small satellite architectures have become a desirable low cost alternative to larger heritage spacecraft for advanced scientific missions. Unfortunately, the...

  17. Alternative Green Technology for Power Generation Using Waste-Heat Energy And Advanced Thermoelectric Materials, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is interested in advancing green technology research for achieving sustainable and environmentally friendly energy sources for both terrestrial and space...

  18. Alternative Green Technology for Power Generation Using Waste-Heat Energy And Advanced Thermoelectric Materials, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is interested in advancing green technology research for achieving sustainable and environmentally friendly energy sources. Thermo-electric power generation...

  19. Prognostic significance of pretherapeutic and therapeutic factors in patients with advanced cancer of the uterine cervix treated with radical radiotherapy alone

    Energy Technology Data Exchange (ETDEWEB)

    Karolewski, K.; Korzeniowski, S.; Urbanski, K.; Kojs, Z. [Centre of Oncology, Maia Sklodowska-Curie Memorial Inst., Krakow (Poland); Sokolowski, A. [Dept. of Statistics, Cracow Univ. of Economics (Poland)

    1999-11-01

    The prognostic importance of various pretherapeutic and therapeutic factors was analysed in a group of 413 cervical cancer patients with stage IIB (183 pts) and IIIB (230 pts) treated with radical radiotherapy, which consisted of external irradiation and intracavitary brachytherapy. Univariate analysis of pretherapeutic factors revealed the prognostic significance of patient age, history of abortion, stage, haemoglobin and hematocrit levels. Five-year overall survival rate in stage IIB patients was 51% in stage IIIB 40% and the respective rates for local control at each stage were 61%, and 46%. Univariate analysis of therapeutic factors showed that survival and local control rates increased with the dose, but a significant difference was found only in the case of a paracentral (point A) dose. In a multivariate analysis only patient age, abortions, and clinical stage appeared to have a significant and independent impact on survival. Linear regression analysis results indicated that prolongation of treatment time between 33 and 108 days caused a loss of local control of 0.36% per day. (orig.)

  20. Somatostatin receptor scintigraphy in advanced renal cell carcinoma. Results of a phase II-trial of somatostatine analogue therapy in patients with advanced RCC

    International Nuclear Information System (INIS)

    Freudenberg, L.S.; Goerges, R.; Stergar, H.; Bockisch, A.; Gauler, T.; Bauer, S.; Antoch, G.; Schuette, J.

    2008-01-01

    Aims: objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin analogue (SST-A) and to assess the response rate under therapy with SST-A. Patients, methods: 16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48h post i.v. injection of 175-200 MBq 111 In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in > 50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR registered -Depot 30mg i.m. every four weeks). Results: in 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In too patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a two-month interval showed progressive disease in both patients. Conclusions: we conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option. (orig.)

  1. Peak medial (but not lateral) hamstring activity is significantly lower during stance phase of running. An EMG investigation using a reduced gravity treadmill.

    Science.gov (United States)

    Hansen, Clint; Einarson, Einar; Thomson, Athol; Whiteley, Rodney

    2017-09-01

    The hamstrings are seen to work during late swing phase (presumably to decelerate the extending shank) then during stance phase (presumably stabilizing the knee and contributing to horizontal force production during propulsion) of running. A better understanding of this hamstring activation during running may contribute to injury prevention and performance enhancement (targeting the specific role via specific contraction mode). Twenty active adult males underwent surface EMG recordings of their medial and lateral hamstrings while running on a reduced gravity treadmill. Participants underwent 36 different conditions for combinations of 50%-100% altering bodyweight (10% increments) & 6-16km/h (2km/h increments, i.e.: 36 conditions) for a minimum of 6 strides of each leg (maximum 32). EMG was normalized to the peak value seen for each individual during any stride in any trial to describe relative activation levels during gait. Increasing running speed effected greater increases in EMG for all muscles than did altering bodyweight. Peak EMG for the lateral hamstrings during running trials was similar for both swing and stance phase whereas the medial hamstrings showed an approximate 20% reduction during stance compared to swing phase. It is suggested that the lateral hamstrings work equally hard during swing and stance phase however the medial hamstrings are loaded slightly less every stance phase. Likely this helps explain the higher incidence of lateral hamstring injury. Hamstring injury prevention and rehabilitation programs incorporating running should consider running speed as more potent stimulus for increasing hamstring muscle activation than impact loading. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Exatecan in pretreated adult patients with advanced soft tissue sarcoma: results of a phase II--study of the EORTC Soft Tissue and Bone Sarcoma Group

    DEFF Research Database (Denmark)

    Reichardt, P; Nielsen, Ole Steen; Bauer, S

    2007-01-01

    No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. Exatecan (DX-8951f) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which...... was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas, has been reported for topoisomerase I-inhibitors, a study with a new and more potent...... agent seemed justified. We report on a prospective multicentre phase II study of Exatecan in adult soft tissue sarcomas failing 1 or 2 lines of chemotherapy in advanced phase, performed within the STBSG of EORTC. Thirty-nine patients (16 leiomyosarcomas and 23 other histologies) were included in two...

  3. Combining Advanced Turbulent Mixing and Combustion Models with Advanced Multi-Phase CFD Code to Simulate Detonation and Post-Detonation Bio-Agent Mixing and Destruction

    Science.gov (United States)

    2017-10-01

    Prepared by: School of Aerospace Engineering, Georgia Institute of Technology 270 Ferst Dr Atlanta, GA 30332...METHOD- OLOGY 7 4.1 Modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 4.1.1 Eulerian Gas Phase...from [3] and our simu- lation : our work is able to capture a non linear behaviour . . . . . . . . . . 59 5.44 Pressure profile from the blast wave

  4. Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Dellas, Kathrin; Dunst, Jürgen; Höhler, Thomas; Reese, Thomas; Würschmidt, Florian; Engel, Erik; Rödel, Claus; Wagner, Wolfgang; Richter, Michael; Arnold, Dirk

    2013-01-01

    Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine. Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m 2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m 2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate. 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection

  5. Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

    OpenAIRE

    Kelly, K; Infante, JR; Taylor, MH; Patel, MR; Wong, DJ; Iannotti, N; Mehnert, JM; Loos, AH; Koch, H; Speit, I; Gulley, JL

    2018-01-01

    © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. BACKGROUND: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. METHODS: Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patient...

  6. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

    International Nuclear Information System (INIS)

    Brizzi, Maria P; Ferretti, Benedetta; Alabiso, Oscar; Ciuffreda, Libero; Bertetto, Oscar; Papotti, Mauro; Dogliotti, Luigi; Berruti, Alfredo; Ferrero, Anna; Milanesi, Enrica; Volante, Marco; Castiglione, Federico; Birocco, Nadia; Bombaci, Sebastiano; Perroni, Davide

    2009-01-01

    Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma. Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m 2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable. Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. NCT00953394

  7. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

    Directory of Open Access Journals (Sweden)

    Ciuffreda Libero

    2009-11-01

    Full Text Available Abstract Background Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU infusion plus long-acting release (LAR octreotide in patients with neuroendocrine carcinoma. Methods Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily plus LAR octreotide (20 mg monthly. Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Results Assessment by Response Evaluation Criteria in Solid Tumors (RECIST criteria showed partial response in 7 (24.1%, stable disease in 20 (69.0%, and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A response was observed in 12/25 assessable patients (48.0%; symptom relief was obtained in 9/15 symptomatic patients (60.0%. There was non significant decrease in circulating vascular epithelial growth factor (VEGF over time. Median time to progression was 22.6 months (range, 2.7-68.5; median overall survival was not reached yet. Toxicity was mild and manageable. Conclusion Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. Trial registration NCT00953394

  8. DEVELOPMENT OF A NOVEL RADIATIVELY/CONDUCTIVELY STABILIZED BURNER FOR SIGNIFICANT REDUCTION OF NOx EMISSIONS AND FOR ADVANCING THE MODELING AND UNDERSTANDING OF PULVERIZED COAL COMBUSTION AND EMISSIONS

    Energy Technology Data Exchange (ETDEWEB)

    Noam Lior; Stuart W. Churchill

    2003-10-01

    The primary objective of the proposed study was the study and analysis of, and design recommendations for, a novel radiatively-conductively stabilized combustion (RCSC) process for pulverized coal, which, based on our prior studies with both fluid fuels and pulverized coal, holds a high promise to reduce NO{sub x} production significantly. We have primarily engaged in continuing and improving our process modeling and analysis, obtained a large amount of quantitative information about the effects of the major parameters on NO{sub x} production, conducted an extensive exergy analysis of the process, evaluated the practicalities of employing the Radiatively-Conductively Stabilized Combustor (RCSC) to large power and heat plants, and improved the experimental facility. Prior experimental work has proven the feasibility of the combustor, but slagging during coal combustion was observed and should be dealt with. The primary outcomes and conclusions from the study are: (1) we developed a model and computer program that represents the pulverized coal combustion in the RCSC, (2) the model predicts that NO{sub x} emissions can be reduced by a number of methods, detailed in the report. (3) the exergy analysis points out at least a couple of possible ways to improve the exergetic efficiency in this combustor: increasing the effectiveness of thermal feedback, and adjusting the combustor mixture exit location, (4) because of the low coal flow rates necessitated in this study to obtain complete combustion in the burner, the size of a burner operating under the considered conditions would have to be up to an order of magnitude, larger than comparable commercial burners, but different flow configurations of the RCSC can yield higher feed rates and smaller dimensions, and should be investigated. Related to this contract, eleven papers were published in journals and conference proceedings, and ten invited presentations were given at university and research institutions, as well as at

  9. End-to-end models for marine ecosystems: Are we on the precipice of a significant advance or just putting lipstick on a pig?

    Directory of Open Access Journals (Sweden)

    Kenneth A. Rose

    2012-02-01

    Full Text Available There has been a rapid rise in the development of end-to-end models for marine ecosystems over the past decade. Some reasons for this rise include need for predicting effects of climate change on biota and dissatisfaction with existing models. While the benefits of a well-implemented end-to-end model are straightforward, there are many challenges. In the short term, my view is that the major role of end-to-end models is to push the modelling community forward, and to identify critical data so that these data can be collected now and thus be available for the next generation of end-to-end models. I think we should emulate physicists and build theoretically-oriented models first, and then collect the data. In the long-term, end-to-end models will increase their skill, data collection will catch up, and end-to-end models will move towards site-specific applications with forecasting and management capabilities. One pathway into the future is individual efforts, over-promise, and repackaging of poorly performing component submodels (“lipstick on a pig”. The other pathway is a community-based collaborative effort, with appropriate caution and thoughtfulness, so that the needed improvements are achieved (“significant advance”. The promise of end-to-end modelling is great. We should act now to avoid missing a great opportunity.

  10. [Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma].

    Science.gov (United States)

    Bi, Ting; Jin, Feng; Wu, Weili; Long, Jinhua; Li, Yuanyuan; Gong, Xiuyun; Luo, Xiuling; Li, Zhuoling; He, Qianyong; Qu, Bo

    2015-09-01

    To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC). Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle. Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in

  11. Next Generation Advanced Binder Chemistries for High Performance, Environmetally DurableThermal Control Material Systems., Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This innovative SBIR Phase I proposal will develop new binder systems through the systematic investigations to tailor required unique performance properties and...

  12. Grid-Free LES 3D Vortex Method for the Simulation of Tubulent Flows Over Advanced Lifting Surfaces, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Turbulent flows associated with advanced aerodynamic designs represent a considerable challenge for accurate prediction. For example, the flow past low-speed wings...

  13. Algorithm Design and Validation for Adaptive Nonlinear Control Enhancement (ADVANCE) Technology Development for Resilient Flight Control, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — SSCI proposes to develop and test a framework referred to as the ADVANCE (Algorithm Design and Validation for Adaptive Nonlinear Control Enhancement), within which...

  14. Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Maurel, Joan; Martin-Richard, Marta; Conill, Carlos; Sanchez, Marcelo; Petriz, Lourdes; Gines, Angels; Miquel, Rosa; Gallego, Rosa; Cajal, Rosana; Ayuso, Carmen; Navarro, Salvador; Marmol, Maribel; Nadal, Cristina; Auge, Josep Maria; Fernandez-Cruz, Laureano; Gascon, Pere

    2006-01-01

    Purpose: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor is overexpressed in pancreatic cancer, and in vitro studies have shown that epidermal growth factor receptor inhibitors can overcome radio- and chemoresistance. The aim of the study was to determine whether the addition of gefitinib to RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe. Methods and Materials: Eighteen patients with pathologically proven LAPC, based on major vascular invasion based on helical computed tomography (CT) and endoscopic ultrasound, were entered into the study. The targeted irradiated volume included the tumor and 2-cm margin. Prophylactic irradiation of regional nodes was not allowed. Patients with >500 cm 3 of planning tumor volume were excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150, and 200 mg/m 2 /day of gemcitabine in a 2-h infusion over Weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers was also performed to evaluate a possible antiangiogenic effect. Results: There were no dose-limiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95% confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5) months, and the median overall survival was 7.5 (95% CI 5.2-9.9) months. No significant reduction of vascular endothelial growth factor and interleukin-8 was observed after treatment. Conclusion: Our results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC

  15. Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

    International Nuclear Information System (INIS)

    Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seok Ah; Lee, Keun Seok; Yun, Tak; Jeong, Seung-Yong; Choi, Hyo Seong; Lim, Seok-Byung; Chang, Hee Jin; Jung, Kyung Hae

    2011-01-01

    Purpose: To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Methods and Materials: Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m 2 1 week before radiotherapy, and then cetuximab 250 mg/m 2 /week, irinotecan 40 mg/m 2 /week for 5 consecutive weeks and capecitabine 1,650 mg/m 2 /day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. Results: In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.

  16. ERCC1, toxicity and quality of life in advanced NSCLC patients randomized in a large multicentre phase III trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2010-01-01

    Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited.......Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited....

  17. Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors.

    Science.gov (United States)

    Zhao, Qiong; Shentu, Jianzhong; Xu, Nong; Zhou, Jianya; Yang, Guangdie; Yao, Yinan; Tan, Fenlai; Liu, Dongyang; Wang, Yingxiang; Zhou, Jianying

    2011-08-01

    The goal of this study was to assess the safety and tolerability of icotinib hydrochloride (BPI-2009H), a new selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), and to explore its pharmacokinetics (PK) and clinical activity in patients with advanced solid tumors, mainly those with non-small-cell lung cancer (NSCLC) after the failure of the prior platinum-based chemotherapy. Different doses of oral icotinib were administered once every 8 h (Q8H) for a 28-continuous-day cycle until disease progression and or undue toxicity was observed. PK studies of subjects' blood were performed during cycle one (day 1 through 28). Patients aged ≥18 and ≤70 years with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and adequate organ functions eligible for the study. Tumor responses were assessed by Response Evaluation Criteria in Solid Tumors (RECIST). K-ras and EGFR mutations in the extracted DNA of fourteen specimens were examined using PCR-based direct sequencing assay. Thirty-six patients were enrolled in the study. PK analysis demonstrated that the mean elimination half-life of icotinib was 6 h, and the T(max) was around 2 h. The steady-state concentration of icotinib administered at a dose of 125 mg once every 8 h (Q8H) was significantly higher than that achieved by a dose of 100mg Q8H. The most frequent treatment-related adverse events (TRAEs) were an acne-like (folliculitis) rash (16/36, 44.4%), diarrhea (8/36, 22.2%) and a decrease in white blood cells (4/36, 11.1%). The maximum-tolerated dose (MTD) was not reached. Among 33 patients with NSCLC, 7 patients exhibited a partial response, 7 showed stable disease at the 24 weeks. Among 14 patients undergoing DNA sequence for K-ras and EGFR mutations, 3 with K-ras mutation presented 2 stable disease (SD) and 1 partial response (PR), 5 with EGFR exon 19 or 21 mutation 2 PR and 3 SD within 4 weeks. Oral icotinib was generally well tolerated, with manageable and

  18. Prospective randomized phase II study of FOLFIRI versus FOLFOX7 in advanced gastric adenocarcinoma: a Chinese Western Cooperative Gastrointestinal Oncology Group Study.

    Science.gov (United States)

    Li, Qiu; Wen, Feng; Zhou, Chengya; Qiu, Meng; Liu, Jiyan; Chen, Jing; Yi, Cheng; Li, Zhiping; Luo, Deyun; Xu, Feng; Cai, Xiaohong; Bi, Feng

    2017-11-17

    Until now, no standard chemotherapy has been widely accepted for advanced gastric cancer (GC). The current research aimed to compare folinic acid, fluorouracil with irinotecan (mFOLFIRI) or with oxaliplatin (mFOLFOX7) as first-line treatments in patients with locally advanced GC in an open, randomized, phase II study. Previously untreated metastatic or recurrent GC patients with measurable disease received mFOLFIRI (arm A) or mFOLFOX7 (arm B) every 2 weeks. The defined second-line treatment was mFOLFOX7 for arm A and mFOLFIRI for arm B. Primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), disease control rate (DCR) and toxicity. The evaluable population consisted of 128 patients (54 in arm A; 74 in arm B). Median PFS of arm A was 2.9 months (m) (95% confidence interval, CI , 1.9 to 4.1 m) versus 4.1 m (95% CI , 3.2 to 4.8 m) for arm B ( p = 0.109). Median OS was 9.9 months (95% CI , 6.0 to 13.5 m) for arm A versus 12.0 m for arm B (95% CI , 10.3 to 13.7m; p = 0.431). DCRs for arm A and arm B were 59.3% and 66.3%, respectively ( p = 0.850). In subgroup analysis of the patients who completed both treatment lines per protocol, the median first-line PFS was 2.1 m for the mFOLFIRI/mFOLFOX7arm versus 8.0 m for the mFOLFOX7/mFOLFIRI arm ( p = 0.053), and the median second-line PFS values were 1.2 m versus 5.1 m ( p = 0.287). Total PFS and OS were 8.1m and 11.0 m for the mFOLFIRI/mFOLFOX7 group compared with 12.2m and 20.2 m for the mFOLFOX7/mFOLFIRI group ( p = 0.008, p = 0.030). Both regimens were well-tolerated with acceptable and manageable toxicities. Hence, there was no significant difference in the PFS or DCR. However, mFOLFOX7 followed by mFOLFIRI might have a better OS.

  19. First-in-human phase 1 of YS110, a monoclonal antibody directed against CD26 in advanced CD26-expressing cancers.

    Science.gov (United States)

    Angevin, Eric; Isambert, Nicolas; Trillet-Lenoir, Véronique; You, Benoit; Alexandre, Jérôme; Zalcman, Gérard; Vielh, Philippe; Farace, Françoise; Valleix, Fanny; Podoll, Thomas; Kuramochi, Yu; Miyashita, Itaru; Hosono, Osamu; Dang, Nam H; Ohnuma, Kei; Yamada, Taketo; Kaneko, Yutaro; Morimoto, Chikao

    2017-04-25

    YS110 is a humanised IgG1 monoclonal antibody with high affinity to the CD26 antigen. YS110 demonstrated preclinical anti-tumour effects without significant side effects. This FIH study was designed to determine the maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) to assess the tolerance, pharmacokinetics (PK) and pharmacodynamics profiles of YS110 and preliminary efficacy. YS110 were initially administered intravenously once every 2 weeks (Q2W) for three doses and then, based on PK data, once every week (Q1W) for five doses in patients with CD26-expressing solid tumours. Thirty-three patients (22 mesothelioma) received a median of 3 (range 1-30) YS110 infusions across six dose levels (0.1-6 mg kg -1 ). MTD was not reached and two dose-limiting toxicities (infusion hypersensitivity reactions) led to the institution of a systemic premedication. Low-grade asthenia (30.3%), hypersensitivity (27.3%), nausea (15.2%), flushing (15.2%), chills (12.1%) and pyrexia (12.1%) were reported as ADRs. Pharmacokinetic parameters (AUC and C max ) increased in proportion with the dose. sCD26/DPPIV assays indicated CD26 modulation. Prolonged stable diseases were observed in 13 out of 26 evaluable patients. YS110 is well tolerated up to 6 mg kg -1 Q1W, which has been defined as the RP2D, with encouraging prolonged disease stabilisations observed in a number of patients with advanced/refractory mesothelioma.

  20. A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification.

    Science.gov (United States)

    Angevin, Eric; Spitaleri, Gianluca; Rodon, Jordi; Dotti, Katia; Isambert, Nicolas; Salvagni, Stefania; Moreno, Victor; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hollebecque, Antoine; Azaro, Analia; Hervieu, Alice; Rihawi, Karim; De Marinis, Filippo

    2017-12-01

    Dysregulated MET signalling is implicated in oncogenesis. The safety and preliminary efficacy of a highly selective MET kinase inhibitor (SAR125844) was investigated in patients with advanced solid tumours and MET dysregulation. This was a phase I dose-escalation (3 + 3 design [50-740 mg/m 2 ]) and dose-expansion study. In the dose escalation, patients had high total MET (t-MET) expression by immunohistochemistry (IHC) or MET amplification by fluorescence in situ hybridisation. In the dose expansion, patients had MET amplification (including a subset of patients with non-small cell lung cancer [NSCLC]) or phosphorylated-MET (p-MET) expression (IHC). Objectives were determination of maximum tolerated dose (MTD) of once-weekly intravenous SAR125844 based on dose-limiting toxicities; safety and pharmacokinetic profile; preliminary efficacy of SAR125844 MTD in the expansion cohort. In total, 72 patients were enrolled: dose escalation, N = 33; dose expansion, N = 39; 570 mg/m 2 was established as the MTD. Most frequent treatment-emergent adverse events (AEs) were asthenia/fatigue (58.3%), nausea (31.9%), and abdominal pain, constipation, and dyspnea (27.8% for each); 58.3% of patients reported grade 3 AEs (19.4% were treatment related). Of the 29 evaluable patients with MET amplification treated at 570 mg/m 2 , five achieved a partial response, including four of 22 with NSCLC; 17 patients had stable disease. No response was observed in patients with high p-MET solid tumours. There was no correlation between tumour response and t-MET status or MET gene copy number. The MTD of once-weekly SAR125844 was 570 mg/m 2 ; SAR125844 was well tolerated, with significant antitumour activity in patients with MET-amplified NSCLC. NCT01391533. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. “Don't let the world become too small” – How patients with advanced cancer and their significant others cope with transitions during the last year of life. A qualitative study

    Science.gov (United States)

    Chabloz-Süssenbach, Christiane; Sailer Schramm, Monique; Stoll, Hansruedi; Spirig, Rebecca

    2016-07-01

    Background: In the last year of life, persons with advanced cancer and their significant others are affected by several transitions. They perform psychological adjustment processes during transformation. This requires strategies for patients and their significant others. Research in German about this theme is missing. Aim: We explored the experiences with illness management during transitions in the last year of life of patients with advanced cancer and their significant others. Method: In this qualitative study, we conducted structured interviews with five dyads, consisting of persons with Karnofsky Index ≥ 60 % and life expectancy of six to twelve months as well as their significant others. To interpret the interviews, we used qualitative content analysis according to Mayring. Results: The main theme “Don't let the world become too small” expresses that limitations diminished the lifeworld and the participants struggled against this process. This is revealed in three categories: “Being shocked by diagnosis – realigning again”, “Bearing limitations and loss – finding new ways in daily life”, “Living in uncertainty – holding out together”. Conclusions: Patients and significant others live in changing lifeworlds caused by transitions. Health care professionals should be attentive and may gain deeper knowledge about transitions. Further research in German-speaking contexts will help to improve nursing care and psychooncological interventions.

  2. Waste incineration models for operation optimization. Phase 1: Advanced measurement equipment for improved operation of waste fired plants; Affaldsforbraendingsmodeller til driftsoptimering. Fase 1: Avanceret maeleudstyr til forbedret drift af affaldsfyrede anlaeg

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-06-01

    This report describes results from the PSO projects ELTRA-5294 and ELTRA-5348: Waste incineration models for operation optimization. Phase 1, and Advanced measurement equipment for improved operation of waste fired plants. Phase 1. The two projects form the first step in a project course build on a long-term vision of a fully automatic system using a wide range of advanced measurement data, advanced dynamic models for prediction of operation and advanced regulation methods for optimization of the operation of waste incinerator plants. (BA)

  3. Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer

    Directory of Open Access Journals (Sweden)

    Asanuma Hiroko

    2008-05-01

    Full Text Available Abstract Background We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer. Methods We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks. Results In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1, and another had general malaise (grade 1 and fever (grade 1. Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD. Immunologically, in 3 of the 10 patients (30%, an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%, although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols. Conclusion This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more

  4. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

    Science.gov (United States)

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

    2015-06-01

    To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

  5. ModelLab: A Cloud-Based Platform to Support Advanced Geospatial Modeling of Earth Observation Data, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In order to promote and facilitate broader use of NASA and other Earth observation data sources, the Phase I research focused on development of a cloud-based...

  6. Advanced Data Mining and Deployment for Integrated Vehicle Health Management and the Space Vehicle Lifecycle, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In a successful Phase 1 project for NASA SBIR topic A1.05, "Data Mining for Integrated Vehicle Health Management," Michigan Aerospace Corporation (MAC) demonstrated...

  7. SiC-SiC and C-SiC Honeycomb for Advanced Flight Structures, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed project builds upon the work done in Phase I with the development of a C-SiC CMC honeycomb material that was successfully tested for mechanical...

  8. Advanced Petroleum-Based Fuels -- Diesel Emissions Control Project (APBF-DEC): Lubricants Project, Phase 2 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    2006-06-01

    This report summarizes the results of the second phase of a lubricants project, which investigated the impact of engine oil formulation on diesel vehicle emissions and the performance of a nitrogen oxide adsorber catalyst (NAC).

  9. SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

    Science.gov (United States)

    Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

    2015-01-01

    Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

  10. Report: ECHO Data Quality Audit – Phase I Results: The Integrated Compliance Information System Needs Security Controls to Protect Significant Non-Compliance Data

    Science.gov (United States)

    Report #09-P-0226, August 31, 2009. End users of the Permit Compliance System and Integrated Compliance Information System National Pollutant Discharge Elimination System can override the Significant Non-Compliance data field without more access controls.

  11. Korea advanced liquid metal reactor development - Development of measuring techniques of the sodium two-phase flow

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moo Hwan; Cha, Jae Eun [Pohang University of Science and Technology, Pohang (Korea)

    2000-04-01

    The technology which models and measures the behavior of bubble in liquid sodium is very important to insure the safety of the liquid metal reactor. In this research, we designed/ manufactured each part and loop of experimental facility for sodium two phase flow, and applied a few possible methods, measured characteristic of two phase flow such as bubbly flow. A air-water loop similar to sodium loop on each measuring condition was designed/manufactured. This air-water loop was utilized to acquire many informations which were necessary in designing the two phase flow of sodium and manufacturing experimental facility. Before the manufacture of a electromagnetic flow meter for sodium, the experiment using each electromagnetic flow mete was developed and the air-water loop was performed to understand flow characteristics. Experiments for observing the signal characteristics of flow were performed by flowing two phase mixture into the electromagnetic flow mete. From these experiments, the electromagnetic flow meter was designed and constructed by virtual electrode, its signal processing circuit and micro electro magnet. It was developed to be applicable to low conductivity fluid very successfully. By this experiment with the electromagnetic flow meter, we observed that the flow signal was very different according to void fraction in two phase flow and that probability density function which was made by statistical signal treatment is also different according to flow patterns. From this result, we confirmed that the electromagnetic flow meter could be used to understand the parameters of two phase flow of sodium. By this study, the experimental facility for two phase flow of sodium was constricted. Also the new electromagnetic flow meter was designed/manufactured, and experimental apparatus for two phase flow of air-water. Finally, this study will be a basic tool for measurement of two phase flow of sodium. As the fundamental technique for the applications of sodium at

  12. Phase II study of cetuximab plus concomitant boost radiotherapy in Japanese patients with locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Okano, Susumu; Yoshino, Takayuki; Fujii, Masato

    2013-01-01

    We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck. Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m 2 initial dose then 250 mg/m 2 weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 2-7: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing ≥70% of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule). Twenty-two patients were evaluable. The treatment completion rate was 100% (95% confidence interval 85-100). The response rate 8 weeks post-radiotherapy was 82% (95% confidence interval 60-95). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73%); dermatitis (27%); and infection, radiation skin injury and stomatitis (23% each). Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck. (author)

  13. Advances in phase space analysis of partial differential equations in honor of Ferruccio Colombini's 60th birthday

    CERN Document Server

    Bove, Antonio; Murthy, MK Venkatesha

    2009-01-01

    This collection of original articles and surveys addresses the recent advances in linear and nonlinear aspects of the theory of partial differential equations. The key topics include operators as "sums of squares" of real and complex vector fields, nonlinear evolution equations, local solvability, and hyperbolic questions.

  14. Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer : A phase II clinical trial

    NARCIS (Netherlands)

    Eisterer, Wolfgang; de Vries, Alexander; Öfner, Dietmar; Rabl, Hans; Koplmüller, Renate; Greil, Richard; Tschmelitsch, Jöerg; Schmid, Rainer; Kapp, Karin; Lukas, Peter; Sedlmayer, Felix; Höfler, Gerald; Gnant, Michael; Thaler, Josef; Widder, Joachim

    2014-01-01

    BACKGROUND/AIM: To investigate the feasibility and safety of preoperative capecitabine, cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer (LARC, cT3/T4). PATIENTS AND METHODS: 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45

  15. Phenobarbital blockade of the preovulatory luteinizing hormone surge: association with phase-advanced circadian clock and altered suprachiasmatic nucleus Period1 gene expression

    Science.gov (United States)

    Legan, Sandra J.; Donoghue, Kathleen M.; Franklin, Kathleen M.; Duncan, Marilyn J.

    2009-01-01

    The suprachiasmatic nucleus (SCN) controls the timing of the preovulatory luteinizing hormone (LH) surge in laboratory rodents. Barbiturate administration during a critical period on proestrus delays the surge and prolongs the estrous cycle 1 day. Because a nonphotic timing signal (zeitgeber) during the critical period that phase advances activity rhythms can also induce the latter effect, we hypothesized that barbiturates delay the LH surge by phase-advancing its circadian timing signal beyond the critical period. In experiment 1, locomotor rhythms and estrous cycles were monitored in hamsters for 2–3 wk preinjection and postinjection of vehicle or phenobarbital and after transfer to darkness at zeitgeber time (ZT) 6 on proestrus. Phenobarbital delayed estrous cycles in five of seven hamsters, which exhibited phase shifts that averaged twofold greater than those exhibited by vehicle controls or phenobarbital-injected hamsters with normal cycles. Experiment 2 used a similar protocol, but injections were at ZT 5, and blood samples for LH determination were collected from 1200 to 1800 on proestrus and the next day via jugular cannulae inserted the day before proestrus. Phenobarbital delayed the LH surge 1 day in all six hamsters, but it occurred at an earlier circadian time, supporting the above hypothesis. Experiment 3 investigated whether phenobarbital, like other nonphotic zeitgebers, suppresses SCN Period1 and Period2 transcription. Two hours postinjection, phenobarbital decreased SCN expression of only Period1 mRNA, as determined by in situ hybridization. These results suggest that phenobarbital advances the SCN pacemaker, governing activity rhythms and hormone release in part by decreasing its Period1 gene expression. PMID:19297538

  16. Performance Evaluation of Advanced Retrofit Roof Technologies Using Field-Test Data Phase Three Final Report, Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Kaushik [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Childs, Phillip W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Atchley, Jerald Allen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-01-01

    This article presents some miscellaneous data from two low-slope and two steep-slope experimental roofs. The low-slope roofs were designed to compare the performance of various roof coatings exposed to natural weatherization. The steep-slope roofs contained different combinations of phase change material, rigid insulation, low emittance surface and above-sheathing ventilation, with standing-seam metal panels on top. The steep-slope roofs were constructed on a series of adjacent attics separated at the gables using thick foam insulation. This article describes phase three (3) of a study that began in 2009 to evaluate the energy benefits of a sustainable re-roofing technology utilizing standing-seam metal roofing panels combined with energy efficient features like above-sheathing-ventilation (ASV), phase change material (PCM) and rigid insulation board. The data from phases 1 and 2 have been previously published and reported [Kosny et al., 2011; Biswas et al., 2011; Biswas and Childs, 2012; Kosny et al., 2012]. Based on previous data analyses and discussions within the research group, additional test roofs were installed in May 2012, to test new configurations and further investigate different components of the dynamic insulation systems. Some experimental data from phase 3 testing from May 2012 to December 2013 and some EnergyPlus modeling results have been reported in volumes 1 and 3, respectively, of the final report [Biswas et al., 2014; Biswas and Bhandari, 2014].

  17. Evidence of significant energy input in the late phase of a solar flare from NuSTAR x-ray observations

    DEFF Research Database (Denmark)

    Kuhar, Matej; Krucker, Säm; Hannah, Iain G.

    2017-01-01

    -size solar flare 1 day before the observations, at ∼18 UT on 2014 December 10, with the post-flare loops still visible at the time of NuSTAR observations. The time evolution of the source emission in the SDO/AIA 335 Å channel reveals the characteristics of an extreme-ultraviolet late-phase event, caused......We present observations of the occulted active region AR 12222 during the third Nuclear Spectroscopic Telescope ARray (NuSTAR) solar campaign on 2014 December 11, with concurrent Solar Dynamics Observatory (SDO)/AIA and FOXSI-2 sounding rocket observations. The active region produced a medium...... by the continuous formation of new post-flare loops that arch higher and higher in the solar corona. The spectral fitting of NuSTAR observations yields an isothermal source, with temperature 3.8–4.6 MK, emission measure (0.3–1.8) × 1046 cm−3, and density estimated at (2.5–6.0) × 108 cm−3. The observed AIA fluxes...

  18. Results of the Workshop on Two-Phase Flow, Fluid Stability and Dynamics: Issues in Power, Propulsion, and Advanced Life Support Systems

    Science.gov (United States)

    McQuillen, John; Rame, Enrique; Kassemi, Mohammad; Singh, Bhim; Motil, Brian

    2003-01-01

    The Two-phase Flow, Fluid Stability and Dynamics Workshop was held on May 15, 2003 in Cleveland, Ohio to define a coherent scientific research plan and roadmap that addresses the multiphase fluid problems associated with NASA s technology development program. The workshop participants, from academia, industry and government, prioritized various multiphase issues and generated a research plan and roadmap to resolve them. This report presents a prioritization of the various multiphase flow and fluid stability phenomena related primarily to power, propulsion, fluid and thermal management and advanced life support; and a plan to address these issues in a logical and timely fashion using analysis, ground-based and space-flight experiments.

  19. Advanced heat pump for the recovery of volatile organic compounds. Phase 1, Conceptual design of an advanced Brayton cycle heat pump for the recovery of volatile organic compounds: Final report

    Energy Technology Data Exchange (ETDEWEB)

    1992-03-01

    Emissions of Volatile Organic Compounds (VOC) from stationary industrial and commercial sources represent a substantial portion of the total US VOC emissions. The ``Toxic-Release Inventory`` of The US Environmental Protection Agency estimates this to be at about 3 billion pounds per year (1987 estimates). The majority of these VOC emissions are from coating processes, cleaning processes, polymer production, fuel production and distribution, foam blowing,refrigerant production, and wood products production. The US Department of Energy`s (DOE) interest in the recovery of VOC stems from the energy embodied in the recovered solvents and the energy required to dispose of them in an environmentally acceptable manner. This Phase I report documents 3M`s work in close working relationship with its subcontractor Nuclear Consulting Services (Nucon) for the preliminary conceptual design of an advanced Brayton cycle heat pump for the recovery of VOC. Nucon designed Brayton cycle heat pump for the recovery of methyl ethyl ketone and toluene from coating operations at 3M Weatherford, OK, was used as a base line for the work under cooperative agreement between 3M and ODE. See appendix A and reference (4) by Kovach of Nucon. This cooperative agreement report evaluates and compares an advanced Brayton cycle heat pump for solvent recovery with other competing technologies for solvent recovery and reuse. This advanced Brayton cycle heat pump is simple (very few components), highly reliable (off the shelf components), energy efficient and economically priced.

  20. EVIDENCE OF SIGNIFICANT ENERGY INPUT IN THE LATE PHASE OF A SOLAR FLARE FROM NuSTAR X-RAY OBSERVATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Kuhar, Matej; Krucker, Säm [University of Applied Sciences and Arts Northwestern Switzerland, Bahnhofstrasse 6, 5210 Windisch (Switzerland); Hannah, Iain G.; Wright, Paul J. [SUPA School of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Glesener, Lindsay [School of Physics and Astronomy, University of Minnesota—Twin Cities, Minneapolis, MN 55455 (United States); Saint-Hilaire, Pascal; Hudson, Hugh S.; Boggs, Steven E.; Craig, William W. [Space Sciences Laboratory, University of California, Berkeley, CA 94720-7450 (United States); Grefenstette, Brian W.; Harrison, Fiona A. [Cahill Center for Astrophysics, 1216 E. California Boulevard, California Institute of Technology, Pasadena, CA 91125 (United States); White, Stephen M. [Air Force Research Laboratory, Albuquerque, NM (United States); Smith, David M.; Marsh, Andrew J. [Physics Department and Santa Cruz Institute for Particle Physics, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (United States); Christensen, Finn E. [DTU Space, National Space Institute, Technical University of Denmark, Elektrovej 327, DK-2800 Lyngby (Denmark); Hailey, Charles J. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Stern, Daniel [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Zhang, William W. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2017-01-20

    We present observations of the occulted active region AR 12222 during the third Nuclear Spectroscopic Telescope ARray ( NuSTAR ) solar campaign on 2014 December 11, with concurrent Solar Dynamics Observatory ( SDO )/AIA and FOXSI-2 sounding rocket observations. The active region produced a medium-size solar flare 1 day before the observations, at ∼18 UT on 2014 December 10, with the post-flare loops still visible at the time of NuSTAR observations. The time evolution of the source emission in the SDO/ AIA 335 Å channel reveals the characteristics of an extreme-ultraviolet late-phase event, caused by the continuous formation of new post-flare loops that arch higher and higher in the solar corona. The spectral fitting of NuSTAR observations yields an isothermal source, with temperature 3.8–4.6 MK, emission measure (0.3–1.8) × 10{sup 46} cm{sup −3}, and density estimated at (2.5–6.0) × 10{sup 8} cm{sup −3}. The observed AIA fluxes are consistent with the derived NuSTAR temperature range, favoring temperature values in the range of 4.0–4.3 MK. By examining the post-flare loops’ cooling times and energy content, we estimate that at least 12 sets of post-flare loops were formed and subsequently cooled between the onset of the flare and NuSTAR observations, with their total thermal energy content an order of magnitude larger than the energy content at flare peak time. This indicates that the standard approach of using only the flare peak time to derive the total thermal energy content of a flare can lead to a large underestimation of its value.

  1. Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seiwert, Tanguy Y., E-mail: tseiwert@medicine.bsd.uchicago.edu [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Melotek, James M. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Blair, Elizabeth A. [Department of Otolaryngology, University of Chicago, Chicago, Illinois (United States); Stenson, Kerstin M. [Department of Otolaryngology, Rush University, Chicago, Illinois (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Witt, Mary Ellyn [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Lingen, Mark W. [Department of Pathology, University of Chicago, Chicago, Illinois (United States); Kocherginsky, Masha [Department of Public Health Sciences, University of Chicago, Chicago, Illinois (United States); Villaflor, Victoria M. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Cohen, Ezra E.W. [Moores Cancer Center, University of California, San Diego, San Diego, California (United States); Haraf, Daniel J. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Vokes, Everett E. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States)

    2016-09-01

    Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

  2. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib: an international, multicentre, prospective, randomised, placebo-controlled phase 3 trial (GRID)

    Science.gov (United States)

    Demetri, George D; Reichardt, Peter; Kang, Yoon-Koo; Blay, Jean-Yves; Rutkowski, Piotr; Gelderblom, Hans; Hohenberger, Peter; Leahy, Michael; von Mehren, Margaret; Joensuu, Heikki; Badalamenti, Giuseppe; Blackstein, Martin; Cesne, Axel Le; Schöffski, Patrick; Maki, Robert G; Bauer, Sebastian; Nguyen, Binh Bui; Xu, Jianming; Nishida, Toshirou; Chung, John; Kappeler, Christian; Kuss, Iris; Laurent, Dirk; Casali, Paolo

    2013-01-01

    Summary Background To date, only two agents, imatinib and sunitinib, have shown clinical benefit in patients with gastrointestinal stromal tumours (GISTs), but almost all metastatic GISTs eventually develop resistance to these agents, resulting in fatal disease progression. This phase 3 trial assessed efficacy and safety of regorafenib in patients with metastatic and/or unresectable GIST progressing after failure of at least imatinib and sunitinib. Methods Patients were randomised 2:1 to receive either regorafenib 160 mg orally daily or placebo, plus best supportive care in both arms, for the first 3 weeks of each 4-week cycle. The primary endpoint was progression-free survival (PFS). Upon disease progression, patients on placebo could cross over to regorafenib. Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR: rate of durable stable disease lasting for ≥12 weeks plus complete or partial responses), and safety. This trial is registered at ClinicalTrials.gov (NCT01271712). Results From January to August 2011, 240 patients were screened at 57 centres in 17 countries, and 199 patients were randomised to receive regorafenib (n=133) or matching placebo (n=66). Median PFS per independent blinded central review was 4·8 months and 0·9 months, respectively (hazard ratio [HR] 0·27, 95% confidence interval [CI] 0·19–0·39; pregorafenib, resulting in no significant difference in OS between study arms (HR 0·77, 95% CI 0·42–1·41; p=0·199). A best response of partial response or stable disease was observed in 101/133 patients (75·9%) on regorafenib and 23/66 patients (34·8%) on placebo. DCR was 52·6% (70/133 patients) and 9·1% (6/66 patients), respectively. Drug-related adverse events were reported in 130 (98·5%) of 132 regorafenib patients and 45 (68·2%) of 66 placebo patients. The most common grade ≥3 regorafenib-related adverse events were hypertension (31/132, 23·5%), hand–foot skin reaction (26

  3. Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

    International Nuclear Information System (INIS)

    Seiwert, Tanguy Y.; Melotek, James M.; Blair, Elizabeth A.; Stenson, Kerstin M.; Salama, Joseph K.; Witt, Mary Ellyn; Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison; Lingen, Mark W.; Kocherginsky, Masha; Villaflor, Victoria M.; Cohen, Ezra E.W.; Haraf, Daniel J.; Vokes, Everett E.

    2016-01-01

    Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

  4. ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia.

    Science.gov (United States)

    Currow, D; Temel, J S; Abernethy, A; Milanowski, J; Friend, J; Fearon, K C

    2017-08-01

    Cancer anorexia-cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities. ROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia. Patients with preserved Eastern Cooperative Oncology Group ≤2 after completing 12 weeks (w) on the ROMANA 1 or ROMANA 2 trials (0-12 weeks) could enroll in ROMANA 3 and continue to receive anamorelin 100 mg or placebo once daily for an additional 12w (12-24 weeks). The primary endpoint of ROMANA 3 was anamorelin safety/tolerability (12-24 weeks). Secondary endpoints included changes in body weight, handgrip strength (HGS), and symptom burden (0-24 weeks). Of the 703 patients who completed ROMANA 1 and ROMANA 2, 513 patients entered ROMANA 3 (anamorelin, N = 345, mean age 62.0 years; placebo, N = 168; mean age 62.2 years). During ROMANA 3, anamorelin and placebo groups had similar incidences of treatment-emergent adverse events (TEAEs; 52.2% versus 55.7%), grade ≥3 TEAEs (22.4% versus 21.6%), and serious TEAEs (12.8% versus 12.6%). There were 36 (10.5%) and 23 (13.8%) deaths in the anamorelin and placebo groups, respectively; none were drug-related. Improvements in body weight and anorexia-cachexia symptoms observed in the original trials were consistently maintained over 12-24 weeks. Anamorelin, versus placebo, significantly increased body weight from baseline of original trials at all time points (P cachexia symptoms at weeks 3, 6, 9, 12, and 16 (P < 0.05). No significant improvement in HGS was seen in either group. During the 12-24 weeks ROMANA 3 trial, anamorelin continued to be well tolerated. Over the entire 0-24w treatment period, body weight and symptom burden were improved

  5. Flight service evaluation of an advanced composite empennage component on commercial transport aircraft. Phase 1: Engineering development

    Science.gov (United States)

    Ary, A.; Axtell, C.; Fogg, L.; Jackson, A.; James, A. M.; Mosesian, B.; Vanderwier, J.; Vanhamersveld, J.

    1976-01-01

    The empennage component selected for this program is the vertical fin box of the L-1011 aircraft. The box structure extends from the fuselage production joint to the tip rib and includes the front and rear spars. Various design options were evaluated to arrive at a configuration which would offer the highest potential for satisfying program objectives. The preferred configuration selected consists of a hat-stiffened cover with molded integrally stiffened spars, aluminum trussed composite ribs, and composite miniwich web ribs with integrally molded caps. Material screening tests were performed to select an advanced composite material system for the Advanced Composite Vertical Fin (ACFV) that would meet the program requirements from the standpoint of quality, reproducibility, and cost. Preliminary weight and cost analysis were made, targets established, and tracking plans developed. These include FAA certification, ancillary test program, quality control, and structural integrity control plans.

  6. An Advanced Computational Approach to System of Systems Analysis & Architecting Using Agent-Based Behavioral Model: Phase 2

    Science.gov (United States)

    2013-11-18

    for each valid interface between the systems. The factor is proportional to the count of feasible interfaces in the meta-architecture framework... proportional to the square root of the sector area being covered by each type of system, plus some time for transmitting data to, and double checking by, the...22] J.-H. Ahn, "An Archietcture Description method for Acknowledged System of Systems based on Federated Architeture ," in Advanced Science and

  7. Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Sudo, Kentaro; Yamaguchi, Taketo; Ishihara, Takeshi; Nakamura, Kazuyoshi; Shirai, Yoshihiko; Nakagawa, Akihiko; Kawakami, Hiroyuki; Uno, Takashi; Ito, Hisao; Saisho, Hiromitsu

    2007-01-01

    Purpose: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m 2 /day. Results: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m 2 /day, 3 at 70 mg/m 2 /day, and 10 at 80 mg/m 2 /day. Though 1 patient at the final dose level (80 mg/m 2 /day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. Conclusions: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m 2 /day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated

  8. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial

    DEFF Research Database (Denmark)

    Ravaud, Alain; Hawkins, Robert; Gardner, Jason P

    2008-01-01

    PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was comp...

  9. A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma

    NARCIS (Netherlands)

    E. van den Neste (Eric); J.-L. André (Jean-Luc); Gastinne, T. (Thomas); A. Stamatoullas (Aspasia); C. Haioun (Corinne); Belhabri, A. (Amine); O. Reman (Oumédaly); O. Casasnovas (O.); H. Ghesquieres; G.E.G. Verhoef (Gregor); Claessen, M.-J. (Marie-José); H.A. Poirel (Hélène A); M.-C. Copin; Dubois, R. (Romain); P. Vandenberghe (Peter); Stoian, I.-A. (Ioanna-Andrea); Cottereau, A.S. (Anne S.); Bailly, S. (Sarah); L. Knoops (Laurent); F. Morschhauser (Frank)

    2018-01-01

    textabstractJAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we

  10. Measurement of the betatron phase advance and betatron amplitude ratio at the SPP-barS collider

    International Nuclear Information System (INIS)

    Bossart, R.; Scandale, W.

    1987-01-01

    A technique for the precise measurement of lattice functions in a hadron collider has been developed. The betatron functions on either side of the two low beta insertions of the SPS collider have been determined from the measured amplitude and phase of horizontal beam oscillations with a peak amplitude of 40 μm. Four directional couplers and four synchronous receivers working at 200 MHz monitor the betatron oscillations of the beam excited by the fast deflectors of the damper. A fast Fourier transform of the signals provides the phase and amplitude ratio of the beam oscillations between any pair of monitors. The relative amplitude and phase of the beam oscillations can be measured with an accuracy of 0 in phase. For achieving such an accuracy a special calibration method has been implemented to determine the propagation times and amplification factors of the measuring equipment, using the intensity signals of the beam itself. The same equipment can be used also for measuring the beam transfer function by injecting white noise into the beam deflectors

  11. Phase II study on paclitaxel in patients with recurrent, metastatic or locally advanced vulvar cancer not amenable to surgery or radiotherapy: a study of the EORTC-GCG (European Organisation for Research and Treatment of Cancer--Gynaecological Cancer Group)

    NARCIS (Netherlands)

    Witteveen, P. O.; van der Velden, J.; Vergote, I.; Guerra, C.; Scarabeli, C.; Coens, C.; Demonty, G.; Reed, N.

    2009-01-01

    No standard treatment options are available for patients with advanced, recurrent or metastatic vulvar carcinoma not amenable for locoregional treatment. In this phase II study, patients with advanced vulvar cancer received paclitaxel (Taxol) every 3 weeks for up to 10 cycles. Primary objective was

  12. Predictors of severe late radiotherapy-related toxicity after hyperfractionated radiotherapy with or without concomitant cisplatin in locally advanced head and neck cancer. Secondary retrospective analysis of a randomized phase III trial (SAKK 10/94)

    International Nuclear Information System (INIS)

    Ghadjar, Pirus; Simcock, Mathew; Zimmermann, Frank; Betz, Michael; Bodis, Stephan; Bernier, Jacques; Studer, Gabriela; Aebersold, Daniel M.

    2012-01-01

    Background and purpose: This secondary analysis was performed to identify predictive factors for severe late radiotherapy (RT)-related toxicity after treatment with hyperfractionated RT +/− concomitant cisplatin in locally advanced head and neck cancer. Materials and methods: Patients were retrospectively analyzed from the previously reported randomized phase III trial: SAKK 10/94. Severe late RT-related toxicity was defined as late RTOG ⩾ grade 3 toxicity starting 3 months after end of RT and/or potential treatment-related death within 3 years of randomization. Results: Two hundred and thirteen randomized patients were analyzed; 84 (39%) experienced severe late RT-related toxicity. With median follow-up of 9.7 years (range, 0.4–15.4 years), median time to severe late RT-related toxicity was 9.6 years. In the univariate Cox proportional hazards model the following variables were associated with severe late RT-related toxicity: advanced N-classification (p < 0.001); technically unresectable disease (p = 0.04); weight loss ratio (p = 0.003); supportive measures (p = 0.009) and severe acute dysphagia (p = 0.001). In the subsequent multivariate analysis all variables except use of supportive measures remained statistically significant. Conclusions: Chemotherapy did not appear to affect severe late RT-related toxicity, but advanced N-classification, technically unresectable disease, weight loss ratio, and severe acute dysphagia were independent predictive factors for severe late RT-related toxicity.

  13. The Significance of Tailored, Web-Based Information on Experiences Regarding Perceived Self-Management in Ovarian Cancer Patients in the Diagnostic Phase-An Experimental Study

    DEFF Research Database (Denmark)

    Thygesen, Marianne Kirstine; Holt, Kamila Adellund; Mogensen, Ole

    2016-01-01

    provided data for statistical analysis. Patients’ difference in change in Sense of Coherence over time was statistically significant in favor of those who had used the website (mean difference 4.42, pwebsite prevented a decrease in self-management of Danish...... of a healthcare-professional developed website, available to both patients and relatives, on patients’ experienced self-management before surgery for ovarian cancer. In an experimental study, Danish women with ovarian cancer were consecutively included if they would participate and had a relative, willing...... to offer attention to the cancer situation. The control group had standard care, the intervention group plus their relatives had additional access to a website with cancer-specific physical, psychical, and practical information. The validated questionnaires Cancer Behavior Inventory and Sense of Coherence...

  14. TP Atlas: integration and dissemination of advances in Targeted Proteins Research Program (TPRP)-structural biology project phase II in Japan.

    Science.gov (United States)

    Iwayanagi, Takao; Miyamoto, Sei; Konno, Takeshi; Mizutani, Hisashi; Hirai, Tomohiro; Shigemoto, Yasumasa; Gojobori, Takashi; Sugawara, Hideaki

    2012-09-01

    The Targeted Proteins Research Program (TPRP) promoted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan is the phase II of structural biology project (2007-2011) following the Protein 3000 Project (2002-2006) in Japan. While the phase I Protein 3000 Project put partial emphasis on the construction and maintenance of pipelines for structural analyses, the TPRP is dedicated to revealing the structures and functions of the targeted proteins that have great importance in both basic research and industrial applications. To pursue this objective, 35 Targeted Proteins (TP) Projects selected in the three areas of fundamental biology, medicine and pharmacology, and food and environment are tightly collaborated with 10 Advanced Technology (AT) Projects in the four fields of protein production, structural analyses, chemical library and screening, and information platform. Here, the outlines and achievements of the 35 TP Projects are summarized in the system named TP Atlas. Progress in the diversified areas is described in the modules of Graphical Summary, General Summary, Tabular Summary, and Structure Gallery of the TP Atlas in the standard and unified format. Advances in TP Projects owing to novel technologies stemmed from AT Projects and collaborative research among TP Projects are illustrated as a hallmark of the Program. The TP Atlas can be accessed at http://net.genes.nig.ac.jp/tpatlas/index_e.html .

  15. In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.

    Science.gov (United States)

    Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian

    2014-08-01

    The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI conditioning regimens for allo-SCT in advanced-phase CML.

  16. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    International Nuclear Information System (INIS)

    Ikeda, Masafumi; Ioka, Tatsuya; Ito, Yoshinori; Yonemoto, Naohiro; Nagase, Michitaka; Yamao, Kenji; Miyakawa, Hiroyuki; Ishii, Hiroshi; Furuse, Junji; Sato, Keiko; Sato, Tosiya; Okusaka, Takuji

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m 2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m 2 /day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of ≥100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  17. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan); Ioka, Tatsuya [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Yonemoto, Naohiro [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan); Nagase, Michitaka [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan); Yamao, Kenji [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan); Miyakawa, Hiroyuki [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan); Ishii, Hiroshi [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan); Furuse, Junji [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan); Sato, Keiko [Kyoto Unit Center, Japan Environment and Children' s Study, Kyoto University Graduate School of Medicine, Kyoto (Japan); Sato, Tosiya [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan); Okusaka, Takuji [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administere