WorldWideScience

Sample records for plateau phase iii

  1. The OPAL phase III microvertex detector

    International Nuclear Information System (INIS)

    De Jong, S.

    1997-01-01

    A description of the OPAL Phase III microvertex detector is given. Special emphasis is put on problems that have been encountered in the installation and operation of the different phases of the OPAL microvertex detector leading to the present Phase III detector and their cures. A short description of the new OPAL radiation monitoring and beam dump system is also given. (orig.)

  2. Repair of potentially lethal damage in unfed plateau phase cultures of Ehrlich ascited tumour cells

    International Nuclear Information System (INIS)

    Illiakis, G.

    1980-01-01

    Plateau phase EAT-cells have been irradiated at different times in the plateau phase and their ability to repair PLD has been measured. A large capacity to repair PLD has been observed if the cultures were kept in the plateau phase for some hours after irradiation before diluting and plating to measure the survival. In combination with theoretical considerations it is concluded that almost all the PLD produced under these conditions can be repaired. The reaction rate of this repair was independent of the dose and the age of the culture. The results also indicate that PLD repair is independent of the intercellular contact of EAT-cells. (author)

  3. Failures in Phase III: Causes and Consequences.

    Science.gov (United States)

    Seruga, Bostjan; Ocana, Alberto; Amir, Eitan; Tannock, Ian F

    2015-10-15

    Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. ©2015 American Association for Cancer Research.

  4. Objectives and methodology of BIOBADASER phase iii.

    Science.gov (United States)

    Sanchez-Piedra, Carlos; Hernández Miguel, M Victoria; Manero, Javier; Roselló, Rosa; Sánchez-Costa, Jesús Tomás; Rodríguez-Lozano, Carlos; Campos, Cristina; Cuende, Eduardo; Fernández-Lopez, Jesús Carlos; Bustabad, Sagrario; Martín Domenech, Raquel; Pérez-Pampín, Eva; Del Pino-Montes, Javier; Millan-Arcineas, Ana Milena; Díaz-González, Federico; Gómez-Reino, Juan Jesús

    2017-09-18

    Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  5. Resistance of plateau-phase human normal and xeroderma pigmentosum fibroblasts to the cytotoxic effect of ultraviolet light

    International Nuclear Information System (INIS)

    Chan, G.L.; Little, J.B.

    1979-01-01

    Clonogenic survival response to 254-nm ultraviolet light was measured in 2 strains of repair-proficient normal human fibroblasts and 4 strains of xeroderma pigmentosum (XP) fibroblasts belonging to complementation groups A, C, D and variant. In all strains except XPA, cells irradiated in plateau phase and subcultured immediately were much more resistant to the lethal effect of UV than cells irradiated in the exponential phase of growth. Typically, 10-20% of plateau-phase cells were extremely resistant. When the cultures were held in plateau phase for 24 h after irradiation and before subculture, there was a further enhancement of survival. By use of a UV-specific endonuclease assay, no difference was found in the number of DNA lesions induced in exponentially growing and plateau cultures by the same dose of UV light. Thus plateau-phase cells appear to be more efficient in their DNA-repair capability than cells in exponential growth. XP group A cells were uniquely found to be deficient in the processes which lead to plateau-phase resistance. Since plateau-phase repair was not lacking in XP groups C, D and variant, it may be related to a DNA-repair process different from that which is responsible for the overall UV sensitivity of these cells. (orig.)

  6. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W R; Mazurek, M; Waber, H N [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J; Erlandson, A C; Hallbeck, L; Pedersen, K [Goeteborg University (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W; Fritz, P; Geyer, S; Geyer, W; Hanschman, G; Kopinke, F D; Poerschmann, J [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A V; Haworth, A; Ilett, D; Linklater, C M; Tweed, C J [AEA Technology plc, Harwell (United Kingdom); Chenery, S R.N.; Kemp, S J; Milodowski, A E; Pearce, J M; Reeder, S; Rochelle, C A; Smith, B; Wetton, P D; Wragg, J [British Geological Survey, Keyworth (United Kingdom); Clark, I D [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E; Hughes, C R [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E K [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H N; Salameh, E [Univ. of Jordan, Amman (Jordan); Lagerblad, B [Cement Institute, Stockholm (Sweden); Longworth, G [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A F [Private consultant, Norwich (United Kingdom); Savage, D [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J A.T. [ed.; Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  7. MAQARIN natural analogue study: phase III

    International Nuclear Information System (INIS)

    Alexander, W.R.; Mazurek, M.; Waber, H.N.; Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K.; Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J.; Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J.; Clark, I.D.; Karlsson, F.; Khoury, H.N.; Salameh, E.; Lagerblad, B.; Longworth, G.; Savage, D.; Smellie, J.A.T.

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH) 2 type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the 'alkali disturbed zone' of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  8. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W R; Mazurek, M; Waber, H N [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J; Erlandson, A C; Hallbeck, L; Pedersen, K [Goeteborg Univ. (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W; Fritz, P; Geyer, S; Geyer, W; Hanschman, G; Kopinke, F D; Poerschmann, J [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A V; Haworth, A; Ilett, D; Linklater, C M; Tweed, C J [AEA Technology plc, Harwell (United Kingdom); Chenery, S R.N.; Kemp, S J; Milodowski, A E; Pearce, J M; Reeder, S; Rochelle, C A; Smith, B; Wetton, P D; Wragg, J [British Geological Survey, Keyworth (United Kingdom); Clark, I D [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E; Hughes, C R [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E K [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H N; Salameh, E [Univ. of Jordan, Amman (Jordan); Lagerblad, B [Cement Inst., Stockholm (Sweden); Longworth, G [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A F [Private consultant, Norwich (United Kingdom); Savage, D [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J A.T. [ed.; Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  9. The Colorado Plateau III: integrating research and resources management for effective conservation

    Science.gov (United States)

    Sogge, Mark K.; van Riper, Charles

    2008-01-01

    Roughly centered on the Four Corners region of the southwestern United States, the Colorado Plateau covers an area of 130,000 square miles. The relatively high semi-arid province boasts nine national parks, sixteen national monuments, many state parks, and dozens of wilderness areas. With the highest concentration of parklands in North America and unique geological and ecological features, the area is of particular interest to researchers. Derived from the Eighth Biennial Conference of Research on the Colorado Plateau, this third volume in a series of research on the Colorado Plateau expands upon the previous two books. This volume focuses on the integration of science into resource management issues, summarizes what criteria make a successful collaborative effort, outlines land management concerns about drought, provides summaries of current biological, sociological, and archaeological research, and highlights current environmental issues in the Four Corner States of Arizona, New Mexico, Colorado, and Utah. With broad coverage that touches on topics as diverse as historical aspects of pronghorn antelope movement patterns through calculating watershed prescriptions to the role of wind-blown sand in preserving archaeological sites on the Colorado River, this volume stands as a compendium of cuttingedge management-oriented research on the Colorado Plateau. The book also introduces, for the first time, tools that can be used to assist with collaboration efforts among landowners and managers who wish to work together toward preserving resources on the Colorado Plateau and offers a wealth of insights into land management questions for many readers, especially people interested in the natural history, biology, anthropology, wildlife, and cultural management issues of the region.

  10. CONVERSION EXTRACTION DESULFURIZATION (CED) PHASE III

    Energy Technology Data Exchange (ETDEWEB)

    James Boltz

    2005-03-01

    This project was undertaken to refine the Conversion Extraction Desulfurization (CED) technology to efficiently and economically remove sulfur from diesel fuel to levels below 15-ppm. CED is considered a generic term covering all desulfurization processes that involve oxidation and extraction. The CED process first extracts a fraction of the sulfur from the diesel, then selectively oxidizes the remaining sulfur compounds, and finally extracts these oxidized materials. The Department of Energy (DOE) awarded Petro Star Inc. a contract to fund Phase III of the CED process development. Phase III consisted of testing a continuous-flow process, optimization of the process steps, design of a pilot plant, and completion of a market study for licensing the process. Petro Star and the Degussa Corporation in coordination with Koch Modular Process Systems (KMPS) tested six key process steps in a 7.6-centimeter (cm) (3.0-inch) inside diameter (ID) column at gas oil feed rates of 7.8 to 93.3 liters per hour (l/h) (2.1 to 24.6 gallons per hour). The team verified the technical feasibility with respect to hydraulics for each unit operation tested and successfully demonstrated pre-extraction and solvent recovery distillation. Test operations conducted at KMPS demonstrated that the oxidation reaction converted a maximum of 97% of the thiophenes. The CED Process Development Team demonstrated that CED technology is capable of reducing the sulfur content of light atmospheric gas oil from 5,000-ppm to less than 15-ppm within the laboratory scale. In continuous flow trials, the CED process consistently produced fuel with approximately 20-ppm of sulfur. The process economics study calculated an estimated process cost of $5.70 per product barrel. The Kline Company performed a marketing study to evaluate the possibility of licensing the CED technology. Kline concluded that only 13 refineries harbored opportunity for the CED process. The Kline study and the research team's discussions

  11. On the inward drift of runaway electrons during the plateau phase of runaway current

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Di, E-mail: hudi-2@pku.edu.cn [School of Physics, Peking University, Beijing 100871 (China); Qin, Hong [Princeton Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08540 (United States); School of Nuclear Science and Technology and Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China)

    2016-03-15

    The well observed inward drift of current carrying runaway electrons during runaway plateau phase after disruption is studied by considering the phase space dynamic of runaways in a large aspect ratio toroidal system. We consider the case where the toroidal field is unperturbed and the toroidal symmetry of the system is preserved. The balance between the change in canonical angular momentum and the input of mechanical angular momentum in such a system requires runaways to drift horizontally in configuration space for any given change in momentum space. The dynamic of this drift can be obtained by integrating the modified Euler-Lagrange equation over one bounce time. It is then found that runaway electrons will always drift inward as long as they are decelerating. This drift motion is essentially non-linear, since the current is carried by runaways themselves, and any runaway drift relative to the magnetic axis will cause further displacement of the axis itself. A simplified analytical model is constructed to describe such inward drift both in the ideal wall case and no wall case, and the runaway current center displacement as a function of parallel momentum variation is obtained. The time scale of such displacement is estimated by considering effective radiation drag, which shows reasonable agreement with the observed displacement time scale. This indicates that the phase space dynamic studied here plays a major role in the horizontal displacement of runaway electrons during plateau phase.

  12. Dose-rate effects in plateau-phase cultures of S3 HeLa and V79 cells

    International Nuclear Information System (INIS)

    Mitchell, J.B.; Bedford, J.S.; Bailey, S.M.

    1979-01-01

    Dose-rate effects on cell survival were studied for log-, fed plateau-, and unfed plateau-phase cultures of V79 and S3 HeLa cells. For log-phase cultures, repair, cell-cycle redistribution, and cell division during exposure can contribute to the overall dose-rate effect, but their relative contributions are difficult to determine. With plateau-phase cultures, the cell-cycle times are greatly lengthened, for those cells that are in cycle. Hence, the contribution to the overall dose-rate effect of cell-cycle redistribution and cell division during the exposure could be minimized using plateau-phase cultures. With respect to the acute dose-survival curves, there was a clear loss in effectiveness when the dose rate was lowered to 154 rad/hr for both fed and unfed plateau-phase HeLa and V79 cells. There was no further reduction in effectiveness per unit dose, however, when the dose rate was reduced to 55 rad/hr. Since there was virtually no cell division or cell-cycle redistribution, it may be that a limit to the repair-dependent dose-rate effect at 37 0 C has been reached at a dose rate of 154 rad/hr

  13. Qinshan Phase III (CANDU) nuclear power project quality assurance

    International Nuclear Information System (INIS)

    Wang Lingen; Du Jinxiang

    2001-01-01

    The completion and implementation of quality assurance system of Qinshan Phase III (CANDU) nuclear power project are presented. Some comments and understanding with consideration of the project characteristics are put forward

  14. Sample exchange/evaluation (SEE) report - Phase III

    International Nuclear Information System (INIS)

    Winters, W.I.

    1996-01-01

    This report describes the results from Phase III of the Sample Exchange Evaluation (SEE) program. The SEE program is used to compare analytical laboratory performance on samples from the Hanford Site's high level waste tanks

  15. The Supercritical Pile Gamma-Ray Burst Model: The GRB Afterglow Steep Decline and Plateau Phase

    Science.gov (United States)

    Sultana, Joseph; Kazanas, D.; Mastichiadis, A.

    2013-01-01

    We present a process that accounts for the steep decline and plateau phase of the Swift X-Ray Telescope (XRT) light curves, vexing features of gamma-ray burst (GRB) phenomenology. This process is an integral part of the "supercritical pile" GRB model, proposed a few years ago to account for the conversion of the GRB kinetic energy into radiation with a spectral peak at E(sub pk) is approx. m(sub e)C(exp 2). We compute the evolution of the relativistic blast wave (RBW) Lorentz factor Gamma to show that the radiation-reaction force due to the GRB emission can produce an abrupt, small (approx. 25%) decrease in Gamma at a radius that is smaller (depending on conditions) than the deceleration radius R(sub D). Because of this reduction, the kinematic criticality criterion of the "supercritical pile" is no longer fulfilled. Transfer of the proton energy into electrons ceases and the GRB enters abruptly the afterglow phase at a luminosity smaller by approx. m(sub p)/m(sub e) than that of the prompt emission. If the radius at which this slow-down occurs is significantly smaller than R(sub D), the RBW internal energy continues to drive the RBW expansion at a constant (new) Gamma and its X-ray luminosity remains constant until R(sub D) is reached, at which point it resumes its more conventional decay, thereby completing the "unexpected" XRT light curve phase. If this transition occurs at R is approx. equal to R(sub D), the steep decline is followed by a flux decrease instead of a "plateau," consistent with the conventional afterglow declines. Besides providing an account of these peculiarities, the model suggests that the afterglow phase may in fact begin before the RBW reaches R is approx. equal to R(sub D), thus providing novel insights into GRB phenomenology.

  16. Electronic construction collaboration system : phase III.

    Science.gov (United States)

    2011-12-01

    This phase of the electronic collaboration project involved two major efforts: 1) implementation of AEC Sync (formerly known as Attolist), a web-based project management system (WPMS), on the Broadway Viaduct Bridge Project and the Iowa Falls Arch Br...

  17. Social Analysis Systems (SAS2) - Phase III

    International Development Research Centre (IDRC) Digital Library (Canada)

    Scaling Up the International Impact of Action Research : Social Analysis ... up the international impact of action research : SAS phase 3; final technical report ... 000 Canadians abroad to work at the local level on various development issues.

  18. Role of repair saturation in the response of plateau-phase Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Braby, L.A.; Nelson, J.M.; Metting, N.F.

    1987-01-01

    Two repair rates are seen in split-dose experiments on starved plateau-phase CHO cells. It has been assumed that this indicates two different processes repairing two distinct types of sublethal damage. However results of experiments at different dose levels are not consistent with models that assume that the damage is entirely sublethal. Another hypothesis that has been considered is the saturation of a repair mechanism having a limited pool of repair enzymes. Such saturation phenomena have been observed in biochemical repair studies and have thus formed the basis for a model of cellular response, which was shown to be capable of producing dose response curves in good agreement with experimental observations. This model can be extended to account for both dose-rate and split-dose effects

  19. Phased uplift of the northeastern Tibetan Plateau inferred from a pollen record from Yinchuan Basin, northwestern China.

    Science.gov (United States)

    Li, Xinling; Hao, Qingzhen; Wei, Mingjian; Andreev, Andrei A; Wang, Junping; Tian, Yanyan; Li, Xiaolei; Cai, Maotang; Hu, Jianmin; Shi, Wei

    2017-12-21

    The uplift of the Tibetan Plateau (TP) significantly affected both regional and global climates. Although there is evidence that the Tibetan Plateau experienced uplift during the Quaternary, the timing and amplitude are poorly constrained. However, the increased availability of long sedimentary records of vegetation change provides an opportunity to reconstruct the timing of the uplift. Here, we present a well-dated, high-resolution pollen record for the last 2.6 Ma from the Yinchuan Basin, which was incised by the Yellow River with its source in the northeastern Tibetan Plateau. Variations in the Artemisia/Chenopodiaceae (A/C) ratio of the reveal changes in moisture conditions in the Yinchuan Basin during glacial-interglacial cycles, as well as a gradual long-term aridification trend which is consistent with progressive global cooling. However, fluctuations in the percentages of Picea and Abies differ from those of the A/C ratio and we propose that they reflect changes in the vegetation and environment of high elevation areas. The Picea and Abies records reveal two phases of increased representation, at 2.1 and 1.2 Ma, which may indicate phases in the uplift of the northeastern Tibetan Plateau. Thus, they provide independent evidence for the timing of the uplift of the Tibetan Plateau during the Quaternary.

  20. Comparison of Time/Phase Lags in the Hard State and Plateau State of GRS 1915+105

    NARCIS (Netherlands)

    Pahari, M.; Neilsen, J.; Yadav, J.S.; Misra, R.; Uttley, P.

    2013-01-01

    We investigate the complex behavior of energy- and frequency-dependent time/phase lags in the plateau state and the radio-quiet hard (χ) state of GRS 1915+105. In our timing analysis, we find that when the source is faint in the radio, quasi-periodic oscillations (QPOs) are observed above 2 Hz and

  1. Two-phase titration of cerium(III) by permanganate

    International Nuclear Information System (INIS)

    Lazarev, A.I.; Lazareva, V.I.; Gerko, V.V.

    1987-01-01

    This paper presents a method for the two-phase titrimetric determination of cerium(III) with permanganate which does not require an expenditure of sugar and preliminary removal of chlorides and nitrates. The interaction of cerium(III) with permanganate at room temperature was studied as a function of the pH, the concentration of pyrophosphate, tetraphenylphosphonium (TPP), permanganate, and extraneous compounds, the rate of titration, and the time of stay of the solution in air before titration. The investigations were conducted according to the following methodology: water, solution of cerium(III) pyrophosphate, and TPP were introduced into an Erlenmeyer flask with a side branch near the bottom for clearer observation of the color of the chloroform phase. The authors established the given pH value, poured the water into a volume of 50 ml, and added chloroform. The result was titrated with permanganate solutions of various concentrations until a violet color appeared in the chloroform phase

  2. Joint probability of statistical success of multiple phase III trials.

    Science.gov (United States)

    Zhang, Jianliang; Zhang, Jenny J

    2013-01-01

    In drug development, after completion of phase II proof-of-concept trials, the sponsor needs to make a go/no-go decision to start expensive phase III trials. The probability of statistical success (PoSS) of the phase III trials based on data from earlier studies is an important factor in that decision-making process. Instead of statistical power, the predictive power of a phase III trial, which takes into account the uncertainty in the estimation of treatment effect from earlier studies, has been proposed to evaluate the PoSS of a single trial. However, regulatory authorities generally require statistical significance in two (or more) trials for marketing licensure. We show that the predictive statistics of two future trials are statistically correlated through use of the common observed data from earlier studies. Thus, the joint predictive power should not be evaluated as a simplistic product of the predictive powers of the individual trials. We develop the relevant formulae for the appropriate evaluation of the joint predictive power and provide numerical examples. Our methodology is further extended to the more complex phase III development scenario comprising more than two (K > 2) trials, that is, the evaluation of the PoSS of at least k₀ (k₀≤ K) trials from a program of K total trials. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Precipitation phase separation schemes in the Naqu River basin, eastern Tibetan plateau

    Science.gov (United States)

    Liu, Shaohua; Yan, Denghua; Qin, Tianling; Weng, Baisha; Lu, Yajing; Dong, Guoqiang; Gong, Boya

    2018-01-01

    Precipitation phase has a profound influence on the hydrological processes in the Naqu River basin, eastern Tibetan plateau. However, there are only six meteorological stations with precipitation phase (rainfall/snowfall/sleet) before 1979 within and around the basin. In order to separate snowfall from precipitation, a new separation scheme with S-shaped curve of snowfall proportion as an exponential function of daily mean temperature was developed. The determinations of critical temperatures in the single/two temperature threshold (STT/TTT2) methods were explored accordingly, and the temperature corresponding to the 50 % snowfall proportion (SP50 temperature) is an efficiently critical temperature for the STT, and two critical temperatures in TTT2 can be determined based on the exponential function and SP50 temperature. Then, different separation schemes were evaluated in separating snowfall from precipitation in the Naqu River basin. The results show that the S-shaped curve methods outperform other separation schemes. Although the STT and TTT2 slightly underestimate and overestimate the snowfall when the temperature is higher and colder than SP50 temperature respectively, the monthly and annual separation snowfalls are generally consistent with the observed snowfalls. On the whole, S-shaped curve methods, STT, and TTT2 perform well in separating snowfall from precipitation with the Pearson correlation coefficient of annual separation snowfall above 0.8 and provide possible approaches to separate the snowfall from precipitation for hydrological modelling.

  4. Research ICT Africa (RIA!) - phase III | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Research ICT Africa (RIA!) - phase III. Depuis la création du réseau RIA! en 2003, ses responsables ont mené avec succès des études portant tant sur l'offre que sur la demande afin de permettre de mieux comprendre l'accès aux TIC et leur utilisation en Afrique. Au cours des deux premières phases du projet (nos 101584 ...

  5. Public Policy and Protection from Exclusion - Phase III | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Public Policy and Protection from Exclusion - Phase III ... and decision-makers active in the promotion of equitable health policies, with a view to promoting the emergence of an observatory of health systems in the ... Policy in Focus publishes a special issue profiling evidence to empower women in the labour market.

  6. Palestinian Adolescents Coping with Trauma (PACT) - Phase III ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Palestinian Adolescents Coping with Trauma (PACT) - Phase III. Violent conflict has been repeatedly shown to result in severe, long-term social and mental health problems for exposed children and adolescents. While in the developed world, it is generally accepted that individuals seek professional one-on-one ...

  7. Differences in inhibition by beta-arabinofuranosyladenine (araA) of radiation induced DNA damage repair in exponentially growing and plateau-phase CHO-cells

    International Nuclear Information System (INIS)

    Iliakis, G.; Seaner, R.

    1988-01-01

    The effect of beta-arabinofuranosyladenine (araA) on the repair of radiation induced DNA damage, as measured by the DNA unwinding technique, was studied in exponentially growing and plateau-phase CHO-cells after exposure to X-rays. Induction of DNA damage by radiation was found to be similar in exponentially growing and plateau-phase cells. In the absence of araA, repair of radiation induced DNA damage proceeded with similar kinetics in exponentially growing and plateau-phase cells. AraA at concentrations between 0-1500 μM inhibited DNA repair both in exponentially growing and in plateau-phase cells. However, the degree of inhibition was significantly higher (by a factor of 3) in plateau-phase cells. A similar degree of repair inhibition by araA was observed in plateau-phase cells treated in their conditioned medium, as well as in plateau-phase cells that were transferred in fresh growth medium just before treatment initiation. These results indicate the importance of biochemical parameters associated with alterations in the growth state of the cells for the inhibitory effect of araA and may help in the elucidation of the molecular mechanism(s) underlying repair inhibition by inhibitors of DNA replication. (orig.)

  8. Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells

    International Nuclear Information System (INIS)

    Igarashi, Kaori; Sakimoto, Ippei; Kataoka, Keiko; Ohta, Keisuke; Miura, Masahiko

    2007-01-01

    The effects of ionizing radiation (IR) on tumor angiogenesis still remain largely unknown. In this study, we found that IR (8 Gy) induces a high-frequency (80-90%) senescence-like phenotype in vascular endothelial cells (ECs) undergoing exponential growth. This finding allowed us to characterize the IR-induced senescence-like (IRSL) phenotype by examining the gene expression profiles and in vitro angiogenic activities of these ECs. The expression levels of genes associated with cell cycle progression and DNA replication were remarkably reduced in the IRSL ECs. Additionally, the in vitro invasion and migration activities of these cells through Matrigel were significantly suppressed. We also found that confluent ECs exhibited a high-frequency IRSL phenotype when they were replated immediately after irradiation, whereas incubation in plateau-phase conditions reduced the induction of this phenotype and enhanced colony formation. The kinetics of DNA double-strand break repair, which showed a faster time course in confluent ECs than in growing ECs, may contribute to the protective mechanism associated with the IRSL phenotype. These results imply that the IRSL phenotype may be important for determining the angiogenic activity of ECs following irradiation. The present study should contribute to the understanding of the effects of IR on tumor angiogenesis

  9. CHAOS. III. GAS-PHASE ABUNDANCES IN NGC 5457

    Energy Technology Data Exchange (ETDEWEB)

    Croxall, Kevin V.; Pogge, Richard W. [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Berg, Danielle A. [Center for Gravitation, Cosmology and Astrophysics, Department of Physics, University of Wisconsin Milwaukee, 1900 East Kenwood Boulevard, Milwaukee, WI 53211 (United States); Skillman, Evan D. [Minnesota Institute for Astrophysics, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455 (United States); Moustakas, John [Department of Physics and Astronomy, Siena College, 515 Loudon Road, Loudonville, NY 12211 (United States)

    2016-10-10

    We present Large Binocular Telescope observations of 109 H ii regions in NGC 5457 (M101) obtained with the Multi-Object Double Spectrograph. We have robust measurements of one or more temperature-sensitive auroral emission lines for 74 H ii regions, permitting the measurement of “direct” gas-phase abundances. Comparing the temperatures derived from the different ionic species, we find: (1) strong correlations of T [N ii] with T [S iii] and T [O iii], consistent with little or no intrinsic scatter; (2) a correlation of T [S iii] with T [O iii], but with significant intrinsic dispersion; (3) overall agreement between T [N ii], T [S ii], and T [O ii], as expected, but with significant outliers; (4) the correlations of T [N ii] with T [S iii] and T [O iii] match the predictions of photoionization modeling while the correlation of T [S iii] with T [O iii] is offset from the prediction of photoionization modeling. Based on these observations, which include significantly more observations of lower excitation H ii regions, missing in many analyses, we inspect the commonly used ionization correction factors (ICFs) for unobserved ionic species and propose new empirical ICFs for S and Ar. We have discovered an unexpected population of H ii regions with a significant offset to low values in Ne/O, which defies explanation. We derive radial gradients in O/H and N/O which agree with previous studies. Our large observational database allows us to examine the dispersion in abundances, and we find intrinsic dispersions of 0.074 ± 0.009 in O/H and 0.095 ± 0.009 in N/O (at a given radius). We stress that this measurement of the intrinsic dispersion comes exclusively from direct abundance measurements of H ii regions in NGC 5457.

  10. Seismic observation of a sharp post-garnet phase transition within the Farallon crust: Evidence for oceanic plateau subduction

    Science.gov (United States)

    Maguire, R.; Ritsema, J.

    2017-12-01

    The tectonic evolution of North America over the past 150 million years was heavily influenced by the complex subduction history of the Farallon plate. In particular, Laramide mountain building may have been triggered by the initiation of flat slab subduction in the late Cretaceous. While it has been proposed that the cause of slab flattening is related to the subduction of an oceanic plateau[1], direct geophysical evidence of a subducted oceanic plateau is lacking. Here, using P-to-S receiver functions, we detect a sharp seismic discontinuity at 720-km depth beneath the southeastern United States and Gulf of Mexico. We interpret this discontinuity as a garnet-to-bridgmanite phase transition occurring within a thickened Farallon crust. Our results are consistent with a subducted oceanic plateau (likely the conjugate half of the Hess rise) which is foundering below the base of the mantle transition zone. Additionally, we find a strong 520-km discontinuity beneath the southeastern United States which may indicate a hydrous transition zone due to the release of H2O from the Farallon slab. These results provide insight into the dynamics of flat slab subduction as well as the tectonic history of North America. [1] Livaccari, R. F., Burke, K., & Şengör, A. M. C. (1981). Was the Laramide orogeny related to subduction of an oceanic plateau? Nature, v. 289, p. 276-278, doi: 10.1038/289276a0

  11. Comparison of time/phase lags in the hard state and plateau state of GRS 1915+105

    Energy Technology Data Exchange (ETDEWEB)

    Pahari, Mayukh; Yadav, J. S. [Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai, India (MP) (India); Neilsen, Joseph [Boston University, Boston, MA 02215 (United States); Misra, Ranjeev [Inter University Center for Astronomy and Astrophysics, Pune (India); Uttley, Phil, E-mail: mp@tifr.res.in [Astronomical Institute, " Anton Pannekoek," University of Amsterdam, Science Park 904, 1098-XH Amsterdam (Netherlands)

    2013-12-01

    We investigate the complex behavior of energy- and frequency-dependent time/phase lags in the plateau state and the radio-quiet hard (χ) state of GRS 1915+105. In our timing analysis, we find that when the source is faint in the radio, quasi-periodic oscillations (QPOs) are observed above 2 Hz and typically exhibit soft lags (soft photons lag hard photons), whereas QPOs in the radio-bright plateau state are found below 2.2 Hz and consistently show hard lags. The phase lag at the QPO frequency is strongly anti-correlated with that frequency, changing sign at 2.2 Hz. However, the phase lag at the frequency of the first harmonic is positive and nearly independent of that frequency at ∼0.172 rad, regardless of the radio emission. The lag energy dependence at the first harmonic is also independent of radio flux. However, the lags at the QPO frequency are negative at all energies during the radio-quiet state, but lags at the QPO frequency during the plateau state are positive at all energies and show a 'reflection-type' evolution of the lag energy spectra with respect to the radio-quiet state. The lag energy dependence is roughly logarithmic, but there is some evidence for a break around 4-6 keV. Finally, the Fourier-frequency-dependent phase lag spectra are fairly flat during the plateau state, but increase from negative to positive during the radio-quiet state. We discuss the implications of our results in light of some generic models.

  12. Superconductivity in the unconventional high pressure phase bismuth-III

    Energy Technology Data Exchange (ETDEWEB)

    Semeniuk, Konstantin; Brown, Philip; Vasiljkovic, Aleksandar; Grosche, Malte [University of Cambridge (United Kingdom)

    2015-07-01

    One of the most surprising developments in high pressure research was the realisation that many elements assume very unexpected high pressure structures, described in terms of extremely large or even infinite unit cells. Elemental bismuth, which has been known to undergo a series of pressure induced structural transitions between 25 kbar and 80 kbar, is an interesting example: the intermediate pressure Bi-III phase has a complex 'host-guest' structure consisting of two incommensurate sublattices. Since the unit cell is infinitely large, the description of electronic and lattice excitations is problematic. Apart from its metallic character and the observation of superconductivity at low temperature, little is known about the electronic structure in this phase. We investigate the electrical resistivity within the metallic Bi-III phase under high hydrostatic pressure and in applied magnetic field using a piston cylinder cell. Superconductivity is observed below 7.1 K, and we extract the temperature dependence of the upper critical field, which exceeds 2 T at low temperature. The normal state resistivity exhibits an approximately linear temperature dependence. This could be attributed to strong scattering from low-lying excitations, as caused by an unusually soft phonon spectrum. The results suggest that strong coupling superconductivity arises within the host-guest structure of Bi-III out of an unusual electronic state.

  13. Aqueous phase complexation of Cm(III) and Cf(III) with ionizable macrocyclic ligands

    International Nuclear Information System (INIS)

    Manchanda, V.K.; Mohapatra, P.K.

    1995-01-01

    Complexation behaviour of Cm(III) and Cf(III) with 1,7-diaza-4,10,13-trioxacyclopentadecane-N,N'-diacetic acid (K21DA), 1,10-diaza-4,7,13,16-tetraoxacyclooctadecane-N,N'-diacetic acid (K22DA) and ethylene diamine N,N'- diacetic acid (EDDA) has been investigated using dinonyl naphthalene sulphonic acid (DNNS), in tetramethyl ammonium form as liquid cation exchanger. The aqueous phase complex formation constants are computed from the distribution data. Though larger complex formation constants are observed with K21DA as well as K22DA compared to those with the acyclic analog EDDA, no size correlation is observed. (author). 5 refs., 1 tab

  14. Solar neutrino oscillation parameters after SNO Phase-III and SAGE Part-III

    International Nuclear Information System (INIS)

    Yang Ping; Liu Qiuyu

    2009-01-01

    We analyse the recently published results from solar neutrino experiments SNO Phase-III and SAGE Part-III and show their constraints on solar neutrino oscillation parameters, especially for the mixing angle θ 12 . Through a global analysis using all existing data from SK, SNO, Ga and Cl radiochemical experiments and long base line reactor experiment KamLAND , we obtain the parameters Δm 12 2 =7.684 -0.208 +0.212 x 10 -5 eV 2 , tan 2 θ 12 =0.440 -0.057 +0.059 . We also find that the discrepancy between the KamLAND and solar neutrino results can be reduced by choosing a small non-zero value for the mixing angle θ 13 . (authors)

  15. Slow growth of the Rayleigh-Plateau instability in aqueous two phase systems

    NARCIS (Netherlands)

    Geschiere, S.D.; Ziemecka, I.; Van Steijn, V.; Koper, G.J.M.; Van Esch, J.H.; Kreutzer, M.T.

    2012-01-01

    This paper studies the Rayleigh-Plateau instability for co-flowing immiscible aqueous polymer solutions in a microfluidic channel. Careful vibration-free experiments with controlled actuation of the flow allowed direct measurement of the growth rate of this instability. Experiments for the

  16. High-Resolution Regional Phase Attenuation Models of the Iranian Plateau and Surrounding Regions

    Science.gov (United States)

    2014-03-03

    crustal structure or sediment thickness across much of the Iranian plateau. The lone exception is the region between the central Zagros and the Lut block...L11303, 2007. Meunier, P., N. Hovius, and J. A. Haines, Topographic site effects and the location of earthquake induced landslides, Earth Planet . Sci

  17. Solid phases limiting the concentration of dissolved constituents in basalt aquifers of the Columbia Plateau in eastern Washington

    International Nuclear Information System (INIS)

    Deutsch, W.J.; Jenne, E.A.; Krupka, K.M.

    1981-01-01

    The purposes of this study were: (1) to provide information on the solid phases which are in apparent equilibrium with ground waters of basalt aquifers, and (2) to further develop the capability of geochemical modeling to support solute transport studies and performance assessments of nuclear waste repositories. The basalt aquifers of the Columbia Plateau in eastern Washington were chosen as the study area because: (1) regional ground-water analyses are readily available, (2) these basalts are a potential medium for a nuclear-waste repository, and (3) mineralogical analyses from local site studies are available

  18. Pipe Overpack Container Fire Testing: Phase I II & III.

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa, Victor G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ammerman, Douglas J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lopez, Carlos [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gill, Walter [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2018-02-01

    The Pipe Overpack Container (POC) was developed at Rocky Flats to transport plutonium residues with higher levels of plutonium than standard transuranic (TRU) waste to the Waste Isolation Pilot Plant (WIPP) for disposal. In 1996 Sandia National Laboratories (SNL) conducted a series of tests to determine the degree of protection POCs provided during storage accident events. One of these tests exposed four of the POCs to a 30-minute engulfing pool fire, resulting in one of the 7A drum overpacks generating sufficient internal pressure to pop off its lid and expose the top of the pipe container (PC) to the fire environment. The initial contents of the POCs were inert materials, which would not generate large internal pressure within the PC if heated. POCs are now being used to store combustible TRU waste at Department of Energy (DOE) sites. At the request of DOE’s Office of Environmental Management (EM) and National Nuclear Security Administration (NNSA), starting in 2015 SNL conducted a series of fire tests to examine whether PCs with combustibles would reach a temperature that would result in (1) decomposition of inner contents and (2) subsequent generation of sufficient gas to cause the PC to over-pressurize and release its inner content. Tests conducted during 2015 and 2016 were done in three phases. The goal of the first phase was to see if the PC would reach high enough temperatures to decompose typical combustible materials inside the PC. The goal of the second test phase was to determine under what heating loads (i.e., incident heat fluxes) the 7A drum lid pops off from the POC drum. The goal of the third phase was to see if surrogate aerosol gets released from the PC when the drum lid is off. This report will describe the various tests conducted in phase I, II, and III, present preliminary results from these tests, and discuss implications for the POCs.

  19. Thermal dewatering of lignite: Phase III - final report

    Energy Technology Data Exchange (ETDEWEB)

    Champagne, P J; Szladow, A J; Kybett, B D

    1981-01-01

    Phase III of this project extended the investigation of thermal dewatering on several lignite and peat samples at the temperature range up to 400 degrees C and investigated variables such as retention time, increased rates of heating and cooling, extent of trace element removal, effect of particle size and effect of dewatering under heavy and light oils. Lignites from three areas of Canada (Estevan and Coronach, Saskatchewan, and Onakawana, Ontario) and one peat sample (Garrick, Saskatchewan) were thermally dewatered. The equilibrium moisture values obtained for the dewatered products were as low as, or lower than those obtained in Phases I and II of this project (350 degrees C). However, the measured moisture contents of the thermally dewatered Saskatchewan lignites were somewhat higher than those measured in Phases I and II. The equilibrium moisture values and the moisture contents decreased with increasing temperature. An optimum balance between extent of dewatering and resulting steam pressures is obtained for a dewatering temperature between 300 and 350 degrees C. At these temperatures, residence times in the order of 15 minutes are required. (35 refs.)

  20. SIMMER-III code-verification. Phase 1

    International Nuclear Information System (INIS)

    Maschek, W.

    1996-05-01

    SIMMER-III is a computer code to investigate core disruptive accidents in liquid metal fast reactors but should also be used to investigate safety related problems in other types of advanced reactors. The code is developed by PNC with cooperation of the European partners FZK, CEA and AEA-T. SIMMER-III is a two-dimensional, three-velocity-field, multiphase, multicomponent, Eulerian, fluid-dynamics code coupled with a space-, time-, and energy-dependent neutron dynamics model. In order to model complex flow situations in a postulated disrupting core, mass and energy conservation equations are solved for 27 density components and 16 energy components, respectively. Three velocity fields (two liquid and one vapor) are modeled to simulate the relative motion of different fluid components. An additional static field takes into account the structures available in a reactor (pins, hexans, vessel structures, internal structures etc.). The neutronics is based on the discrete ordinate method (S N method) coupled into a quasistatic dynamic model. The code assessment and verification of the fluid dynamic/thermohydraulic parts of the code is performed in several steps in a joint effort of all partners. The results of the FZK contributions to the first assessment and verification phase is reported. (orig.) [de

  1. Radiotherapy in carcinoma of the uterine cervix phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez Villa, O; Reinerio, A; Felipe Castillo, A; Alonso Pantiga, R; Roig, M

    1985-01-01

    Between April 1968 and December 1980, 61 patients with phase III cancer of the cervix were treated. Fifty-six of them were squamous-cell carcinomas and five adenocarcinomas. The treatment consisted of a combination of external irradiation at doses varying between 4,000 and 7,000 rads and intracavitary radiotherapy with doses of 4.000 to 6.000 MHz, according to the schemes of the D.M. Anderson of Houston. The results obtained as far as survival is concerned and calculated by the actuarial method were 40% after five and ten years. The local control rate reached was 74%. The severe complications caused by the treatment reached 8.1%.

  2. Effects of low dose rate γ-rays on cell proliferation and survival in exponentially growing and plateau phase cultures of normal rat kidney cells

    International Nuclear Information System (INIS)

    Tsuboi, A.

    1982-01-01

    The effects of 60 Co γ-rays on cell clonogenicity and cell proliferation were examined in NRK cells in exponential and plateau growth phases during and after irradiation at various dose rates. The typical dese rate effect for the survival responses was observed between acute irradiation and continuous irradiation at dose rates of 9.6-44 rads/h. Similar dose rate effect for the perturbation of the proliferation was observed in exponentially growing cells during irradiation. Some differences were found in survival when the cells were exposed to γ-rays at 9.6 rads/h or at 13.7 rads/h. The survival curves of exponential phase cells irradiated at these dose rates showed a shape different from that observed in plateau phase cells. Namely, a steady state of survival appeared around an accumulated dose of 1000 rads (dose-rate of 9.6 rads/h) and an accumulated dose of 1500 rads (dose-rate of 13.7 rads/h) in the exponential phase cells, while such a steady state of survival was not detected in plateau phase cells after similar conditions of irradiation. Moreover, the extrapolation number of the survival curve was much larger at the lower dose rate in exponential phase cells, in contrast to a value of the unity oberved in plateau phase cells, The radiosensitivity of plateau phase cells was somewhat lower compared to exponential phase cells over the range of accumulated doses at the dose rates used. These differences in cellular responses to the radiation between the two phases could be explained by changes in cell proliferation, the redistribution of the cell cycle compartments and the repair capacity of cellular damage during irradiation. (author)

  3. Probability of success for phase III after exploratory biomarker analysis in phase II.

    Science.gov (United States)

    Götte, Heiko; Kirchner, Marietta; Sailer, Martin Oliver

    2017-05-01

    The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success. We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out. We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Los Angeles International Airport Runway Incursion Studies: Phase III--Center-Taxiway Simulation

    Science.gov (United States)

    Madson, Michael D.

    2004-01-01

    Phase III of the Los Angeles International Airport Runway Incursion Studies was conducted, under an agreement with HNTB Corporation, at the NASA Ames FutureFlight Central (FFC) facility in June 2003. The objective of the study was the evaluation of a new center-taxiway concept at LAX. This study is an extension of the Phase I and Phase II studies previously conducted at FFC. This report presents results from Phase III of the study, in which a center-taxiway concept between runways 25L and 25R was simulated and evaluated. Phase III data were compared objectively against the Baseline data. Subjective evaluations by participating LAX controllers were obtained with regard to workload, efficiency, and safety criteria. To facilitate a valid comparison between Baseline and Phase III data, the same scenarios were used for Phase III that were tested during Phases I and II. This required briefing participating controllers on differences in airport and airline operations between 2001 and today.

  5. Synchronous drought and flooding in southern Chinese Loess Plateau in phase with the variation of global temperature

    Science.gov (United States)

    Yu, X.; Kang, Z.

    2017-12-01

    Drought and flooding, usually occurring in the catchment scale, are the main natural threats to human livelihood due to the extreme variation of precipitation in spatiotemporal scales. Within the context of global warming, the risk of flood and drought tends to increase in different regions. Understanding the mechanism of the regional occurrence of flood and drought is of enormous importance for the predicting studies and taking corresponding measures. However, the instrumental records are too short to conduct a prediction. Here, we present a historical-archive-based high-resolution dataset of drought and flooding back to AD 1646 in the southern Chinese Loess Plateau. This sequence, integrated with the modern meteorological observation data, shows that the frequency of drought and flooding in the study region is synchronous on a decadal scale, and they are in phase with the increase in both global and regional temperature. During the warm period, the ENSO activity was found to be increase, resulting in the anomaly distribution of precipitation in different seasons in southern Chinese Loess Plateau, which is the reason for the temperature dependence of flooding and drought in this region. If global temperature continues to rise in the future, the risk of both drought and flooding in the study area would also increase.

  6. 78 FR 73555 - Deepwater Horizon Oil Spill; Draft Programmatic and Phase III Early Restoration Plan and Draft...

    Science.gov (United States)

    2013-12-06

    ... Environmental Impact Statement (Draft Phase III ERP/PEIS). The Draft Phase III ERP/PEIS considers programmatic... programmatic restoration alternatives. The Draft Phase III ERP/PEIS evaluates these restoration alternatives... the Framework Agreement. The Draft Phase III ERP/PEIS also evaluates the environmental consequences of...

  7. Raindrop Size Distribution Measurements at 4,500 m on the Tibetan Plateau During TIPEX-III

    Science.gov (United States)

    Chen, Baojun; Hu, Zhiqun; Liu, Liping; Zhang, Guifu

    2017-10-01

    As part of the third Tibetan Plateau Atmospheric Scientific Experiment field campaign, raindrop size distribution (DSD) measurements were taken with a laser optical disdrometer in Naqu, China, at 4,508 m above sea level (asl) during the summer months of 2013, 2014, and 2015. The characteristics of DSDs for five different rain rates, for two rain types (convective and stratiform), and for daytime and nighttime rains were studied. The shapes of the averaged DSDs were similar for different rain rates, and the width increased with rainfall intensity. Little difference was found in stratiform DSDs between day and night, whereas convective DSDs exhibited a significant day-night difference. Daytime convective DSDs had larger mass-weighted mean diameters (Dm) and smaller generalized intercepts (NW) than the nighttime DSDs. The constrained relations between the intercept N0 and shape μ, slope Λ and μ, and NW and Dm of gamma DSDs were derived. We also derived empirical relations between Dm and the radar reflectivity factor in the Ku and Ka bands.

  8. Dose fractionation effects in plateau-phase cultures of C3H 10T1/2 cells and their transformed counterparts

    International Nuclear Information System (INIS)

    Zeman, E.M.; Bedford, J.S.

    1985-01-01

    A comparison of γ-ray dose fractionation effects was made using plateau-phase cultures of C3H 10T1/2 cells and their transformed counterparts in an attempt to simulate basically similar populations of cells that differ primarily in their turnover rates. The status of cell populations with respect to their turnover rates may be an important factor influencing dose fractionation effects in early- and late-responding tissues. In this cell culture system, the rate of cell turnover was approximately three times higher for the plateau-phase transformed cultures. While the single acute dose survival curves for log-phase cells were indistinguishable, there were significant differences between the survival curves for plateau-phase cultures of the two cell types. Both cell lines had a similar capacity for repair of sublethal damage, but untransformed cells had a much greater capacity to repair potentially lethal damage in plateau phase. Multifraction survival curves were determined for both cell lines for doses per fraction ranging from 9.0 to 0.8 Gy, and from these isoeffect curves of log total dose versus dose per fraction were derived. The isoeffect curve for the slowly cycling, untransformed cells was found to be appreciably steeper than that for the more rapidly cycling transformed cells, a finding consistent with previously reported differences in dose fractionation isoeffect curves for early- and late-responding tissues in vivo

  9. Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

    1988-09-01

    The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage.

  10. Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

    International Nuclear Information System (INIS)

    Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

    1988-01-01

    The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage. (author)

  11. Cyprus natural analogue project (CNAP). Phase III final report

    International Nuclear Information System (INIS)

    Alexander, W.R.; Milodowski, A.E.; Pitty, A.F.

    2012-01-01

    The CNAP Phase III project was carried out following identification of the requirement to support ongoing laboratory and modelling efforts on the potential reaction of the bentonite buffer with cementitious leachates in the repository EBS. Although it is known that the higher pH (12.5 to 13) leachates from OPC cement will degrade bentonite, it is unclear if this will also be the case for the lower pH (10 to 11) leachates typical of low alkali cements. Ongoing laboratory and URL programmes which are currently investigating this face the obstacle of slow kinetics and the production of short-lived metastable phases, meaning obtaining unambiguous results may take decades. This is exacerbated by the limitations of the thermodynamic databases for minerals of interest to models of bentonite/low alkali cement leachate reaction. It was therefore decided to implement a focussed NA study on bentonite/low alkali cement leachate reaction to provide indications of likely long-term reaction products and reaction pathways to provide feedback on the existing short-term investigations noted above and to ascertain if any critical path R and D needs to be instigated now. The results of the analyses presented here suggest that there has been very limited alkaline groundwater reaction with the bentonite. This is generally supported by both the geomorphological evidence and the natural decay series data which imply groundwater groundwater/rock interaction in the last 10 5 a. When integrated with the novel data currently being produced in the BIGRAD project, the CNAP data tend to indicate that any long-term bentonite reaction in low alkali cement leachates is minimal. (orig.)

  12. Cyprus natural analogue project (CNAP). Phase III final report

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W R [Bedrock Geosciences, Auenstein (Switzerland); Milodowski, A E [British Geological Survey, Keyworth (United Kingdom); Pitty, A F [Pitty (EIA) Consulting, Norwich (United Kingdom)

    2012-01-15

    The CNAP Phase III project was carried out following identification of the requirement to support ongoing laboratory and modelling efforts on the potential reaction of the bentonite buffer with cementitious leachates in the repository EBS. Although it is known that the higher pH (12.5 to 13) leachates from OPC cement will degrade bentonite, it is unclear if this will also be the case for the lower pH (10 to 11) leachates typical of low alkali cements. Ongoing laboratory and URL programmes which are currently investigating this face the obstacle of slow kinetics and the production of short-lived metastable phases, meaning obtaining unambiguous results may take decades. This is exacerbated by the limitations of the thermodynamic databases for minerals of interest to models of bentonite/low alkali cement leachate reaction. It was therefore decided to implement a focussed NA study on bentonite/low alkali cement leachate reaction to provide indications of likely long-term reaction products and reaction pathways to provide feedback on the existing short-term investigations noted above and to ascertain if any critical path R and D needs to be instigated now. The results of the analyses presented here suggest that there has been very limited alkaline groundwater reaction with the bentonite. This is generally supported by both the geomorphological evidence and the natural decay series data which imply groundwater groundwater/rock interaction in the last 10{sup 5} a. When integrated with the novel data currently being produced in the BIGRAD project, the CNAP data tend to indicate that any long-term bentonite reaction in low alkali cement leachates is minimal. (orig.)

  13. Evaluate fundamental approaches to longwall dust control. Phase III report

    Energy Technology Data Exchange (ETDEWEB)

    Babbitt, C.; Bartlett, P.; Kelly, J.; Ludlow, J.; Mangolds, A.; Rajan, S.; Ruggieri, S.; Varga, E.

    1984-03-31

    The overall objective of the contract is to evaluate the effectiveness of available dust control technology for double-drum shearer longwall sections in a coordinated, systematic program at a few longwall test sections and to make the results available to the entire coal mining industry. This program is investigating nine different dust control techniques. These nine subprograms encompass a broad range of dust control measures ranging from administrative controls to new hardware. They span not only presently employed methods but also those recently adopted in the United States and those proposed for the future. This report documents the Phase III effort on each of the subprograms. For clarity, the report is divided in sections by subprogram as follows: Section 2, Subprogram A - passive barriers/spray air movers for dust control; Section 3, Subprogram B - practical aspects of deep cutting; Section 4, Subprogram C - stage loader dust control; Section 5, Subprogram D - longwall automation technology; Section 6, Subprogram E - longwall application of ventilation curtains; Section 7, Subprogram F - reversed drum rotation; Section 8, Subprogram G - reduction of shield generated dust; Section 9, Subprogram H - air canopies for longwalls; and Section 10, Subprogram I - mining practices. 43 figures, 11 tables.

  14. Brush Day & Night Phase III to Phase IV: ensuring that good oral health habits are sustainable.

    Science.gov (United States)

    Melo, Paulo; Fine, Charlotte; Malone, Sinead; Horn, Virginie

    2018-05-01

    Over the past 10 years, the FDI-Unilever Brush Day & Night partnership has significantly influenced the life of children worldwide through the implementation of school programmes for oral health education and prevention. This article reports the key facts and outcomes of Phase III of the partnership, and announces the launch of Phase IV. During Phase III, the expert advisors of the Brush Day & Night partnership conducted a longitudinal study to evaluate the impact of the '21 Day' programme in almost 8,000 children in 10 countries. Analysis revealed the effectiveness of the 21 Day programme in sustainably educating children to brush their teeth twice a day, with the greatest impact observed in children aged 7-9 years. With the launch of Phase IV, the Brush Day & Night partnership will continue to deliver its oral health school programme for 7-9 year-old children with a strengthened methodology, including randomized sampling and control groups. The scope of the evaluation will be broadened to include oral health-related quality of life indicators, and monitoring of the oral health knowledge of children's parents/carers. © 2018 FDI World Dental Federation.

  15. EXPERIMENTAL RESULTS OF THE NEPHELINE PHASE III STUDY

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K.; Edwards, T.

    2009-11-09

    This study is the third phase in a series of experiments designed to reduce conservatism in the model that predicts the formation of nepheline, a crystalline phase that can reduce the durability of high level waste glass. A Phase I study developed a series of glass compositions that were very durable while their nepheline discriminator values were well below the current nepheline discriminator limit of 0.62, where nepheline is predicted to crystallize upon slow cooling. A Phase II study selected glass compositions to identify any linear effects of composition on nepheline crystallization and that were restricted to regions that fell within the validation ranges of the Defense Waste Processing Facility (DWPF) Product Composition Control System (PCCS) models. However, it was not possible to identify any linear effects of composition on chemical durability performance for this set of study glasses. The results of the Phase II study alone were not sufficient to recommend modification of the current nepheline discriminator. It was recommended that the next series of experiments continue to focus not only on compositional regions where the PCCS models are considered applicable (i.e., the model validation ranges), but also be restricted to compositional regions where the only constraint limiting processing is the current nepheline discriminator. Two methods were used in selecting glasses for this Phase III nepheline study. The first was based on the relationship of the current nepheline discriminator model to the other DWPF PCCS models, and the second was based on theory of crystallization in mineral and glass melts. A series of 29 test glass compositions was selected for this study using a combination of the two approaches. The glasses were fabricated and characterized in the laboratory. After reviewing the data, the study glasses generally met the target compositions with little issue. Product Consistency Test results correlated well with the crystallization analyses in

  16. THE FUNCTIONAL OUTCOME OF MANAGEMENT OF SCHATZKER TYPE II AND III TIBIAL PLATEAU FRACTURES TREATED WITH INDIRECT ELEVATION, PERCUTANEOUS FIXATION AND BONE GRAFTING

    Directory of Open Access Journals (Sweden)

    Sheshagiri

    2016-02-01

    Full Text Available INTRODUCTION Damage to the joint is more extensive in tibia plateau fractures than the roentgenograms Indicate. It may be associated with soft tissue trauma, ligament injuries (4-33% medial Collateral ligament being the most common, meniscal injuries (20%, lateral collateral Ligament injury (3%, peroneal nerve injuries (3%. Posttraumatic arthritis is associated with residual instability or axial malalignment rather than joint depression. So we use minimally invasive approach to the depressed tibial plateau fractures (Schatzker type II & III. MATERIALS AND METHODS 32 patients were studied. They were followed up for maximum of 3yrs and a minimum of 1.5yrs with an average of 2.2yrs. Inclusion criteria included those patients with an age group between 20yrs and 60yrs, joint depression more than 3mm. Patients with open fracture, severe osteoporotic bones and with radiographic evidence of osteoarthritis are excluded from the study. CT was done in all patients. Mean age group was 28.8yrs and 19(76% were males; the mean articular depression was 11.32 mm measured in CT. Pre-op evaluation includes x-rays of the knee, stress x-rays if needed, and CT was done with 2mm limited cuts. Cancellous Bone graft was taken from opposite tibia through a 3-4cm long incision made below the tibial tuberosity over the medial aspect of the tibia. Cortical window was made in the affected limb, just enough to introduce the punch, and its position was confirmed under c-arm and depressed fragment was elevated with punch and reduction was held with k wires in subarticular plane and later two cannulated cancellous screws was introduced and the defect packed with bone grafts, Post-operatively all patients were immobilized with plaster of Paris (POP for 3 weeks and then mobilized. RESULTS The mean duration of the follow up was 2.2yrs. Results were excellent in 21 patients (84%, good 3(12% and fair in 1 patients (4% according to anatomic and functional criteria by Hohl and Luck

  17. CIM5 Phase III base process development results

    International Nuclear Information System (INIS)

    Witt, D.C.

    2000-01-01

    Integrated Demonstration Runs for the Am/Cm vitrification process were initiated in the Coupled 5-inch Cylindrical Induction Melter (CIM5) on 11/30/98 and completed on 12/9/98. Four successful runs at 60 wt% lanthanide loading were completed which met or exceeded all established criteria. The operating parameters used in these runs established the base conditions for the 5-inch Cylindrical Induction Melter (CIM5) process and were summarized in the 5-inch CIM design basis, SRT-AMC-99-OO01. (1) In subsequent tests, a total of fourteen CIM5 runs were performed using various power inputs, ramp rates and target temperatures to define the preferred processing conditions (2) Process stability and process flexibility were the key criteria used in assessing the results for each run. A preferred set of operating parameters was defined for the CIM5 batch process and these conditions were used to generate a pre-programmed, automatic processing cycle that was used for the last six CIM.5 runs (3) These operational tests were successfully completed in the January-February time frame and were summarized in SRT-AMC-99-00584. The recommended set of operating conditions defined in Runs No.1 through No.14 was used as the starting point for further pilot system runs to determine the robustness of the process, evaluate a bubbler, and investigate off-normal conditions. CIM5 Phase III Runs No.15 through No.60 were conducted utilizing the pre-programmed, automatic processing cycle to investigate system performance. This report summarizes the results of these tests and provides a recommendation for the base process as well as a processing modification for minimizing volume expansions if americium and/or curium are subject to a thermal reduction reaction like cerium. This document summarizes the results of the base process development tests conducted in the Am/Cm Pilot Facility located in Building 672-T

  18. Phase 0 and phase III transport in various organs: combined concept of phases in xenobiotic transport and metabolism.

    Science.gov (United States)

    Döring, Barbara; Petzinger, Ernst

    2014-08-01

    The historical phasing concept of drug metabolism and elimination was introduced to comprise the two phases of metabolism: phase I metabolism for oxidations, reductions and hydrolyses, and phase II metabolism for synthesis. With this concept, biological membrane barriers obstructing the accessibility of metabolism sites in the cells for drugs were not considered. The concept of two phases was extended to a concept of four phases when drug transporters were detected that guided drugs and drug metabolites in and out of the cells. In particular, water soluble or charged drugs are virtually not able to overcome the phospholipid membrane barrier. Drug transporters belong to two main clusters of transporter families: the solute carrier (SLC) families and the ATP binding cassette (ABC) carriers. The ABC transporters comprise seven families with about 20 carriers involved in drug transport. All of them operate as pumps at the expense of ATP splitting. Embedded in the former phase concept, the term "phase III" was introduced by Ishikawa in 1992 for drug export by ABC efflux pumps. SLC comprise 52 families, from which many carriers are drug uptake transporters. Later on, this uptake process was referred to as the "phase 0 transport" of drugs. Transporters for xenobiotics in man and animal are most expressed in liver, but they are also present in extra-hepatic tissues such as in the kidney, the adrenal gland and lung. This review deals with the function of drug carriers in various organs and their impact on drug metabolism and elimination.

  19. The role of technology in reducing health care costs. Phase II and phase III.

    Energy Technology Data Exchange (ETDEWEB)

    Cilke, John F.; Parks, Raymond C.; Funkhouser, Donald Ray; Tebo, Michael A.; Murphy, Martin D.; Hightower, Marion Michael; Gallagher, Linda K.; Craft, Richard Layne, II; Garcia, Rudy John

    2004-04-01

    In Phase I of this project, reported in SAND97-1922, Sandia National Laboratories applied a systems approach to identifying innovative biomedical technologies with the potential to reduce U.S. health care delivery costs while maintaining care quality. The effort provided roadmaps for the development and integration of technology to meet perceived care delivery requirements and an economic analysis model for development of care pathway costs for two conditions: coronary artery disease (CAD) and benign prostatic hypertrophy (BPH). Phases II and III of this project, which are presented in this report, were directed at detailing the parameters of telemedicine that influence care delivery costs and quality. These results were used to identify and field test the communication, interoperability, and security capabilities needed for cost-effective, secure, and reliable health care via telemedicine.

  20. Removal of radiation damage by subpopulations of plateau-phase Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Nelson, J.M.; Metting, N.F.; Braby, L.A.; Roesch, W.C.

    1987-01-01

    Specific cellular radiobiology studies are often required to test aspects of the mathematical models developed in the Radiation Dosimetry program. These studies are designed to determine whether specific mathematical expressions, which characterize the expected effect of biochemical mechanisms on observable biological responses, are consistent with the behavior of selected cell lines. Since these tests place stringent requirements on the cellular system, special techniques and culture conditions are required to minimize biological variability. The use of specialized cell populations is providing data on the extent of repair following low doses, and on the changes in the types of damage that can be repaired as the cell progresses toward mitosis. The stationary-phase Chinese hamster ovary (CHO) cells are composed primarily of G(1)-phase cells (83%), with the remainder comprising both G(2) and S phases. Removal of radiation damage by cells was studied in split-dose experiments. To date, we have observed no significant differences in cellular repair rate. This suggests, therefore, that each of the repair processes found in stationary-phase cells is cell-age independent. However, cellular radiation sensitivity does change rapidly and considerably as the cells progress from one phase to the next through the cell cycle. Since the rate of damage removal appears invariant, the change in survival must reflect the efficiency of producing that damage. The experimental data suggest that production of one or another sort of damage probably dominates during specific phases of the cell cycle, while the capacity for removal of all types of damage remains relatively constant

  1. Spiny Neurons of Amygdala, Striatum and Cortex Use Dendritic Plateau Potentials to Detect Network UP States

    Directory of Open Access Journals (Sweden)

    Katerina D Oikonomou

    2014-09-01

    Full Text Available Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: [1] they are the most abundant cell type within their respective brain area, [2] covered by thousands of thorny protrusions (dendritic spines, [3] possess high levels of dendritic NMDA conductances, and [4] experience sustained somatic depolarizations in vivo and in vitro (UP states. In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (dendritic UP states characterized by (i fast rise, (ii plateau phase lasting several hundred milliseconds and (iii abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates towards the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200 – 800 ms steady depolarization (~20 mV amplitude, which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states. We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.

  2. Phase III Simplified Integrated Test (SIT) results - Space Station ECLSS testing

    Science.gov (United States)

    Roberts, Barry C.; Carrasquillo, Robyn L.; Dubiel, Melissa Y.; Ogle, Kathryn Y.; Perry, Jay L.; Whitley, Ken M.

    1990-01-01

    During 1989, phase III testing of Space Station Freedom Environmental Control and Life Support Systems (ECLSS) began at Marshall Space Flight Center (MSFC) with the Simplified Integrated Test. This test, conducted at the MSFC Core Module Integration Facility (CMIF), was the first time the four baseline air revitalization subsystems were integrated together. This paper details the results and lessons learned from the phase III SIT. Future plans for testing at the MSFC CMIF are also discussed.

  3. Characterization of rapid recovery from γ-ray damage in plateau-phase human diploid fibroblasts

    International Nuclear Information System (INIS)

    Malcolm, A.W.; Tomkinson, K.N.; Little, J.B.

    1982-01-01

    Rapid recovery was investigated in density-inhibited, stationary-phase human diploid cells subcultured to low density at various times after a single dose of radiation. The influence of total dose, postirradiation temperature, and cell-to-cell contact on recovery was examined. The cultures were exposed to 60 Co γ rays at a dose rate of 50 rad per second. When the irradiation and postirradiation temperatures were maintained at 25 or 37 0 C, recovery, as manifested by an enhancement in survival, was similar during the first 30 min, whereas it was reduced at later times in the 25 0 C compared with the 37 0 C cultures. This result suggests the existence of different rapidly and slowly acting components to recovery. No recovery was noted at any time with incubation at 4 0 C. The recovery observed in density-inhibited cultures was consistently greater than that in less dense cultures, suggesting an effect of cell-to-cell contact and cell cycle distribution. Following single doses of 200 to 900 rad, progressive enhancement in relative recovery occurred with increasing doses over a period of 2 to 90 min, illustrating the importance of the relationship of the dose to the rapid recovery process

  4. Effects of caffeine on X-irradiated synchronous, asynchronous and plateau phase mouse ascites cells: the importance of progression through the cell cycle for caffeine enhancement of killing

    International Nuclear Information System (INIS)

    Iliakis, G.; Nuesse, M.

    1983-01-01

    Caffeine potentiated the killing effect of X-rays on exponentially growing cells giving rise to exponential curves (D 0 =(0.8+-0.05)Gy) at 4mM and 14 hours treatment. Irradiated plateau phase cells were less sensitive. Exponentially growing cells also became less sensitive to the effects of caffeine when they were incubated in the conditioned medium of plateau phase cells(C-medium) in which cell growth was considerably inhibited. Low caffeine concentrations(2mM) enhanced X-ray induced killing of cells irradiated in G 1 -,G 1 /S- or S-phase, but more effectively G 2 -phase cells. High caffeine concentrations (6mM) enhanced killing of cells in all phases of the cell cycle. Incubation of synchronized populations in C-medium during treatment with caffeine (2mM and 6mM) resulted in less potentiation than in cells treated in fresh medium. The expression of X-ray induced potentially lethal damage caused by 6mM caffeine in cells irradiated in various phases resulted in an exponential survival curve with a mean lethal dose of (0.8+-0.05)Gy, but the time of caffeine treatment necessary to reach this curve was different for cells irradiated in different phases. PLD repair, measured as loss of sensitivity to 6mM caffeine (4 hours treatment) was of 1-2 hours duration. (author)

  5. The coupling of thermochemistry and phase diagrams for group III-V semiconductor systems. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, T.J.

    1998-07-21

    The project was directed at linking the thermochemical properties of III-V compound semiconductors systems with the reported phase diagrams. The solid-liquid phase equilibrium problem was formulated and three approaches to calculating the reduced standard state chemical potential were identified and values were calculated. In addition, thermochemical values for critical properties were measured using solid state electrochemical techniques. These values, along with the standard state chemical potentials and other available thermochemical and phase diagram data, were combined with a critical assessment of selected III-V systems. This work was culminated with a comprehensive assessment of all the III-V binary systems. A novel aspect of the experimental part of this project was the demonstration of the use of a liquid encapsulate to measure component activities by a solid state emf technique in liquid III-V systems that exhibit high vapor pressures at the measurement temperature.

  6. Urban Ecosystem Health in Kathmandu (Nepal) - Phase III | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The two earlier phases of this project (003320 and 101277) led to the creation or strengthening of 18 local stakeholder groups and resulted in a new Animal Slaughtering and Meat Inspection Act, modification of the Nepal Food Act, modification of the Garbage Disposal Act, revisions to the Kathmandu Valley Housing Plan ...

  7. Research ICT Africa - Phase III | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    During this phase, RIA will construct an African index of ICT policy and regulations; establish a network structure suitable for growth and the integration of North Africa; refine its policy influence and dissemination strategy; integrate its supply- and demand-side data and triangulate it with the telecommunication regulatory ...

  8. Research ICT Africa - Phase III | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Launched in 2003, Research ICT Africa (RIA) has successfully conducted demand- and supply-side studies with a view to better understanding information and communication technology (ICT) access and usage in Africa. The network expanded over the first two phases of support (101584 and 103114) to include members ...

  9. Unraveling the Mystery of the Blue Fog: Structure, Properties, and Applications of Amorphous Blue Phase III.

    Science.gov (United States)

    Gandhi, Sahil Sandesh; Chien, Liang-Chy

    2017-12-01

    The amorphous blue phase III of cholesteric liquid crystals, also known as the "blue fog," are among the rising stars in materials science that can potentially be used to develop next-generation displays with the ability to compete toe-to-toe with disruptive technologies like organic light-emitting diodes. The structure and properties of the practically unobservable blue phase III have eluded scientists for more than a century since it was discovered. This progress report reviews the developments in this field from both fundamental and applied research perspectives. The first part of this progress report gives an overview of the 130-years-long scientific tour-de-force that very recently resulted in the revelation of the mysterious structure of blue phase III. The second part reviews progress made in the past decade in developing electrooptical, optical, and photonic devices based on blue phase III. The strong and weak aspects of the development of these devices are underlined and criticized, respectively. The third- and-final part proposes ideas for further improvement in blue phase III technology to make it feasible for commercialization and widespread use. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Individualized Inservice Teacher Education (Project In-Step). Evaluation Report. Phase III.

    Science.gov (United States)

    Thurber, John C.

    This is a report on the third phase of Project IN-STEP, which was intended to develop a viable model for individualized, multi-media in-service teacher education programs. (Phase I and II are reported in ED 033 905, and ED 042 709). The rationale for Phase III was to see if the model could be successfully transferred to an area other than teaching…

  11. CENTRAL PLATEAU REMEDIATION

    International Nuclear Information System (INIS)

    ROMINE, L.D.

    2006-01-01

    A systematic approach to closure planning is being implemented at the Hanford Site's Central Plateau to help achieve the goal of closure by the year 2035. The overall objective of Central Plateau remediation is to protect human health and the environment from the significant quantity of contaminated material that resulted from decades of plutonium production in support of the nation's defense. This goal will be achieved either by removing contaminants or placing the residual contaminated materials in a secure configuration that minimizes further migration to the groundwater and reduces the potential for inadvertent intrusion into contaminated sites. The approach to Central Plateau cleanup used three key concepts--closure zones, closure elements, and closure process steps--to create an organized picture of actions required to complete remediation. These actions were merged with logic ties, constraints, and required resources to produce an integrated time-phased schedule and cost profile for Central Plateau closure. Programmatic risks associated with implementation of Central Plateau closure were identified and analyzed. Actions to mitigate the most significant risks are underway while high priority remediation projects continue to make progress

  12. Comprehensive Evaluation of the Geothermal Resource Potential within the Pyramid Lake Paiute Reservation Phase III Report

    Energy Technology Data Exchange (ETDEWEB)

    Noel, Donna [Pyramid Lake Paiute Tribe, Nixon, NV (United States)

    2013-12-01

    This project integrated state-of-the-art exploration technologies with a geologic framework and reservoir modeling to ultimately determine the efficacy of future geothermal production within the PLPT reservation. The information gained during this study should help the PLPT to make informed decisions regarding construction of a geothermal power plant. Additional benefits included the transfer of new technologies and geothermal data to the geothermal industry and it created and/or preserved nearly three dozen jobs accordance with the American Recovery and Reinvestment Act of 2009. A variety of tasks were conducted to achieve the above stated objectives. The following are the tasks completed within the project: 1. Permitting 2. Shallow temperature survey 3. Seismic data collection and analysis 4. Fracture stress analysis 5. Phase I reporting Permitting 7. Shallow temperature survey 8. Seismic data collection and analysis 9. Fracture stress analysis 10. Phase I reporting 11. Drilling two new wells 12. Borehole geophysics 13. Phase II reporting 14. Well testing and geochemical analysis 15. Three-dimensional geologic model 16. Three-dimensional reservoir analysis 17. Reservation wide geothermal potential analysis 18. Phase III reporting Phase I consisted of tasks 1 – 5, Phase II tasks 6 – 8, and Phase III tasks 9 – 13. This report details the results of Phase III tasks. Reports are available for Phase I, and II as separate documents.

  13. Brazing of the Tore Supra actively cooled Phase III Limiter

    International Nuclear Information System (INIS)

    Nygren, R.E.; Walker, C.A.; Lutz, T.J.; Hosking, F.M.; McGrath, R.T.

    1993-01-01

    The head of the water-cooled Tore Supra Phase 3 Limiter is a bank of 14 round OFHC copper tubes, curved to fit the plasma radius, onto which several hundred pyrolytic graphite (PG) tiles and a lesser number of carbon fiber composite tiles are brazed. The small allowable tolerances for fitting the tiles to the tubes and mating of compound curvatures made the brazing and fabrication extremely challenging. The paper describes the fabrication process with emphasis on the procedure for brazing. In the fixturing for vacuum furnace brazing, the tiles were each independently clamped to the tube with an elaborate set of window frame clamps. Braze quality was evaluated with transient heating tests. Some rebrazing was necessary

  14. Phase III (full scale) agitated mixing test plan

    International Nuclear Information System (INIS)

    Ruff, D.T.

    1994-01-01

    Waste Receiving and Processing Facility Module 2A (WRAP 2A) is the proposed second module of the WRAP facility. This facility will provide the required treatment for contact Handled (CH) Low Level (LL) Mixed Waste (MW) to allow its permanent disposal. Solidification of a portion of this waste using a cement based grout has been selected in order to reduce the toxicity and mobility of the waste in the disposal site. Mixing of the waste with the cement paste and material handling constraints/requirements associated with the mixed material is, therefore, a key process in the overall treatment strategy. This test plan addresses Phase 3, Full Scale Testing. The objectives of these tests are to determine if there are scale-up issues associated with the mixing results obtained in Phase 1 and 2 mixing tests, verify the workability of mixtures resulting from previous formulation development efforts (Waste Immobilization Development [WID]), and provide a baseline for WRAP 2A mixing equipment design. To this end, the following objectives are of particular interest: determine geometric influence of mixing blade at full scale (i.e., size, type, and location: height/offset); determine if similar results in terms of mixing effectiveness and product quality are achievable at this scale; determine if vibration is as effective at this larger scale in fluidizing the mixture and aiding in cleaning the vessel; determine if baffles or sweeping blades are needed to aid in mixing at the larger size and for cleaning the vessel; and determine quality of the poured monolithic product and investigate exotherm and filling influences at this larger size

  15. Use of Geothermal Energy for Aquaculture Purposes - Phase III

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, W C; Smith, K C

    1981-09-01

    This project, financed by the Pacific Northwest Regional Commission (PNRC), was designed to provide information to evaluate the best methods to use for intensive aquaculture of freshwater prawns, Macrobrachium rosenbergii, using geothermal energy. The freshwater prawn is a tropical organism and is native to southeast Asia. Earlier projects at Oregon Institute of Technology have shown the feasibility of culturing this aquatic animal in geothermal water. This phase of the project was designed to investigate intensive culture of this animal as well as the advantages of growing rainbow trout, ornamental tropical fin fish, and mosquito fish, Gambusia affnis, for vector control using geothermal energy. The research data collected on the prawns was obtained from the stocking and sampling of two 0.2- ha (half-acre) ponds constructed as a part of the project. The ponds are equipped with recording monitors for temperature and flow. The geothermal energy used is the geothermal effluent from the Oregon Institute of Technology heating system. This water is of potable quality and ranges in temperature from 50 to 70oC. The geothermal water used in the ponds is controlled at 27oC, ± 2oC, by using thermostats and solenoid valves. A small building next to the ponds contains facilities for hatching larvae prawns and tanks for growing post-larvae prawns. The hatchery facility makes the project self-sustaining. The hatchery was obtained as part of an earlier PNRC project.

  16. Durability of lightweight concrete : Phase II : wetting and drying tests, Phase III : freezing and thawing tests.

    Science.gov (United States)

    1966-12-01

    This report describes a laboratory research program on the durability of lightweight concrete. Two phases of a three phase study are covered by this report, while the remaining phase is still under study. The two phases being reported are Phase II - ...

  17. Remedial Action Report for Operable Units 6-05 and 10-04, Phase III

    Energy Technology Data Exchange (ETDEWEB)

    R. P. Wells

    2007-08-15

    This Phase III remedial action report addresses the remediation of lead-contaminated soils found at the Security Training Facility STF-02 Gun Range at the Idaho National Laboratory Site. Phase I, consisting of developing and implementing institutional controls at Operble Unit 10-04 sites and developing and implementing Idaho National Laboratory Site-wide plans for both institutional controls and ecological monitoring, was addressed in a previous report. Phase II will remediate sites contaminated with trinitrotoluene and Royal Demolition Explosive. Phase IV will remediate hazards from unexploded ordnance.

  18. Reversed phase partition chromatographic separation of Gd(III) on poly(Crown Ether) column

    International Nuclear Information System (INIS)

    Mahanwar, K.R.; Sabale, S.R.

    2014-01-01

    A simple method has been developed for the separation of Gd(III) in hippuric acid medium by using poly(dibenzo-18-crown-6) as stationary phase. The effect of hippuric acid concentration, different eluting agent, foreign ions etc was studied and the optimum conditions were established. Breakthrough capacity of poly(dibenzo-18-crown-6) for Gd(III) was found to be 0.572 ±0.01 mmolg -1 of crown polymer. The separation of Gd(III) from other elements in multicomponent mixtures has been achieved. The method was extended for determination of Gd(III) in real sample. The method is simple, rapid and selective with good reproducibility (approximately ± 2%). Crown ethers are widely used as complexing agent that can selectively capture metal cation in their cavity. This special feature shown by poly (dibenzo-18-crown-6) has been used in our laboratory for selective cation exchanger by column chromatography. No attempts were made for the separation of Gd(III) using hippuric acid media and column chromatography. The present communication describes a simple and sensitive method for the determination of Gd(III) using poly(dibenzo-18-crown-6) as stationary phase in hippuric acid medium. The proposed method affords an attractive feature as compared to the solvent extraction technique i.e. it is free from any organic diluents as an environmental concern

  19. Effects of PECS Phase III Application Training on Independent Mands in Young Children with Autism

    Science.gov (United States)

    Love, Jessica June

    2013-01-01

    The purpose of this study was to examine the effects of PECS phase III application training on independent mands in young children with autism. Participants were five children with autism ranging from ages 2 to 4 years old. A multiple baseline across participants was used to evaluate acquisition of independent correct mands across baseline and…

  20. SPSP Phase III Recruiting, Selecting, and Developing Secure Power Systems Professionals. Job Profiles

    Energy Technology Data Exchange (ETDEWEB)

    O' Neil, Lori Ross [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Conway, T. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tobey, D. H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Greitzer, Frank L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dalton, Angela C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Pusey, Portia K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-03-01

    The Secure Power Systems Professional Phase III final report was released last year which an appendix of Job Profiles. This new report is that appendix broken out as a standalone document to assist utilities in recruiting and developing Secure Power Systems Professionals at their site.

  1. SPSP Phase III Recruiting, Selecting, and Developing Secure Power Systems Professionals. Individual and Team Performance Guidelines

    Energy Technology Data Exchange (ETDEWEB)

    O' Neil, Lori Ross [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Conway, T. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tobey, D. H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Greitzer, Frank L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dalton, Angela C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Pusey, Portia K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-03-01

    The Secure Power Systems Professional Phase III final report was released last year which an appendix of Individual and Team Performance Guidelines. This new report is that appendix broken out as a standalone document to assist utilities in recruiting and developing Secure Power Systems Professionals at their site.

  2. Acceptance test procedure, 241-SY-101 Flexible Receiver System, Phase III testing

    International Nuclear Information System (INIS)

    Ritter, G.A.

    1994-01-01

    This Acceptance Test Procedure is for the 241-SY-101 Flexible Receiver System, Phase III Testing. This procedure will test the sealing integrity of the Flexible Receiver System to ensure that release of waste and aerosols will be minimized during the removal of the test mixer pump from tank SY-101

  3. Explorations of new phases in the Ga(III)/In(III)-Mo(VI)-Se(IV)/Te(IV)-O systems.

    Science.gov (United States)

    Kong, Fang; Hu, Chun-Li; Hu, Ting; Zhou, Yong; Mao, Jiang-Gao

    2009-07-07

    Systematic explorations of new phases in the Ga(III)/In(III)-Mo(VI)-Se(IV)/Te(IV)-O systems by hydrothermal syntheses or solid-state reactions at high-temperature led to four new quaternary compounds, namely, Ga(2)MoQ(2)O(10) (Q = Se, Te), In(2)Mo(2)Se(2)O(13)(H(2)O) and In(2)MoTe(2)O(10). Ga(2)MoQ(2)O(10) (Q = Se, Te) are isostructural and their structures feature a 3D network of gallium selenite/tellurite with 12-member ring tunnels along b-axis, the distorted MoO(6) octahedra are attached on the wall of the above tunnels. The structure of In(2)Mo(2)Se(2)O(13)(H(2)O) features a new pillared-layered architecture composed of 2D indium(III) selenite layers that are interconnected by Mo(2)O(10) dimers, forming 8-membered ring tunnels along the b-axis. The structure of In(2)MoTe(2)O(10) features a 2D indium oxide layer formed by corner- and edge-sharing InO(6) and InO(7) polyhedra with MoO(4) tetrahedra and TeO(n) (n = 4, 5) polyhedra hanging on both sides of the layer, there are weak interlayer Te-O bonds of 2.512 A. Results of optical diffuse reflectance spectrum measurements indicate that all four compounds are insulators, which are in agreement with results of band structure calculations based on DFT methods.

  4. A Study on Recovery from Potentially Lethal Damage induced by γ-Irradiation in Plateau-phase Vero Cells in vitro

    International Nuclear Information System (INIS)

    Kim, Il Han; Choi, Eun Kyung; Ha, Sung Whan; Park, Charn Il; Cha, Chang Yong

    1988-01-01

    Recovery from potentially lethal damage (PLDR) after irradiation was studied in plateau-phase culture of Vero cells in vitro. Unfed plateau-phase cells were irradiated with dose of 1 to 9 Gy using Cs-137 irradiator. Cells then were incubated again and left in situ for 0, 1, 2, 3, 4, 5, 6 and 24 hours and then were trypsinized, explanted, and subcultured in fresh RPMI-1640 media containing 0.33% agar. Cell survival was measured by colony forming ability. An adequate number of heavily irradiated Vero cells were added as feeder cells to make the total cell number constant in every culture dish. As the postirradiation in situ incubation time increased, surviving fraction increased saturation level at 2 to 4 hours after in situ incubation. As the radiation dose increased, the rate of PLDR also increased. In analysis of cell survival curve fitted to the linear-quadratic model, the linear inactivation coefficient (a) decreased largely and reached nearly to zero but the quadratic inactivation coefficient (b) increased minimally by increment of postirradiation in situ incubation time. So PLDR mainly affected the damage expressed as a. In the multitarget model, significant change was not obtained in D0 but in Dq. Therefore, shoulder region in cell survival curve was mainly affected by PLDR and terminal slope was not influenced at all. And dose-modifying factor by PLDR was relatively higher in shoulder region, that is, in low dose area below 3 Gy

  5. Effects of β-arabinofuranosyladenine on potentially lethal damage induced in plateau phase mammalian cells exposed to U.V.-light

    International Nuclear Information System (INIS)

    Iliakis, G.

    1983-01-01

    The effect of β-arabinofuranosyladenine (β-araA), a specific inhibitor of DNA polymerases α and β, on the survival of plateau phase Ehrlich ascites tumour cells after U.V.-exposure has been studied. β-araA inhibited repair of U.V.-induced potentially lethal damage (PLD), when given to the cells after irradiation. An exponential survival curve (D 0 = 1 J/m 2 ) was obtained when irradiated cells were treated with β-araA at 120 μM. β-araA mainly affected the shoulder width of the survival curve but also changed the slope of the resistant 'tail' of the survival curve. The effect was irreversible at 80 μM and partly reversible at 20 μM. When β-araA was added to cultures in fresh or conditioned medium at 80 μM at various times after irradiation, there was a gradual decrease in PLD. Survival reached levels corresponding to those of untreated cells plated immediately after irradiation. If cells were incubated for additional times in fresh medium, survival increased to levels corresponding to those obtained with plateau phase cells after delayed plating, but did not occur in cells incubated in conditioned medium. The repair time constant for PLD was about 3 hours for cells incubated in fresh medium and about 6 hours incubated in conditioned medium. (author)

  6. Scale-Up Information for Gas-Phase Ammonia Treatment of Uranium in the Vadose Zone at the Hanford Site Central Plateau

    Energy Technology Data Exchange (ETDEWEB)

    Truex, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Szecsody, James E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhong, Lirong [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Thomle, Jonathan N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Johnson, Timothy C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-09-01

    Uranium is present in the vadose zone at the Hanford Central Plateau and is of concern for protection of groundwater. The Deep Vadose Zone Treatability Test Plan for the Hanford Central Plateau identified gas-phase treatment and geochemical manipulation as potentially effective treatment approaches for uranium and technetium in the Hanford Central Plateau vadose zone. Based on laboratory evaluation, use of ammonia vapor was selected as the most promising uranium treatment candidate for further development and field testing. While laboratory tests have shown that ammonia treatment effectively reduces the mobility of uranium, additional information is needed to enable deployment of this technology for remediation. Of importance for field applications are aspects of the technology associated with effective distribution of ammonia to a targeted treatment zone, understanding the fate of injected ammonia and its impact on subsurface conditions, and identifying effective monitoring approaches. In addition, information is needed to select equipment and operational parameters for a field design. As part of development efforts for the ammonia technology for remediation of vadose zone uranium contamination, field scale-up issues were identified and have been addressed through a series of laboratory and modeling efforts. This report presents a conceptual description for field application of the ammonia treatment process, engineering calculations to support treatment design, ammonia transport information, field application monitoring approaches, and a discussion of processes affecting the fate of ammonia in the subsurface. The report compiles this information from previous publications and from recent research and development activities. The intent of this report is to provide technical information about these scale-up elements to support the design and operation of a field test for the ammonia treatment technology.

  7. Enantiomeric separation of iridium (III) complexes using HPLC chiral stationary phases based on amylose derivatives

    International Nuclear Information System (INIS)

    Kim, Hee Eun; Seo, Na Hyeon; Hyun, Myung Ho

    2016-01-01

    Cyclometalated iridium (III) complexes formed with three identical cyclometalating (C-N) ligands (homoleptic) or formed with two cyclometalating (C-N) ligands and one ancillary (LX) ligand (heteroleptic) have been known as highly phosphorescent materials and, thus, they have been utilized as efficient phosphorescent dopants in organic light emitting diodes (OLEDs) 1–3 or as effective phosphorescent chemosensors. 4–7 Cylometalated iridium (III) complexes are chiral compounds consisting of lambda (Λ, left-handed) and delta (Δ, right-handed) isomers. Racemic cyclometa- lated iridium (III) complexes emit light with no net polarization, but optically active cyclometalated iridium (III) complexes emit circularly polarized light. 8,9 Circularly polarized light can be used in various fields including highly efficient three dimensional electronic devices, photo nic devices for optical data storage, biological assays, and others. 8,9 In order to obtain optically active cylometalated iridium (III) complexes and to determine the enantiomeric composition of optically active cylometalated iridium (III) complexes, liquid chromatogr aphic enantiomer separation method on chiral stationary phases (CSPs) has been used. For example, Okamoto and coworkers first reported the high performance liquid chromatographic (HPLC) direct enantiomeric separation of two homoleptic cylometalated iridium (III) complexes on immobilized amylose tris(3,5- dimethylphenylcarbamate) (Chiralpak IA), coated cellulose tris(3,5-dimethylphenylcarbamate) (Chiralc el OD), and coated cellulose tris(4-methylbenzoate) (Chiralce l OJ). 10 Supercritical fluid chromatography (SFC) was also used by Bernhard and coworkers for the enantiomeric separation of cylometalated iridium (III) complexes on coated amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H). 8 However, the general use of the HPLC method for the direct enantiomeric separation of homoleptic

  8. Enantiomeric separation of iridium (III) complexes using HPLC chiral stationary phases based on amylose derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Eun; Seo, Na Hyeon; Hyun, Myung Ho [Dept. of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan (Korea, Republic of)

    2016-12-15

    Cyclometalated iridium (III) complexes formed with three identical cyclometalating (C-N) ligands (homoleptic) or formed with two cyclometalating (C-N) ligands and one ancillary (LX) ligand (heteroleptic) have been known as highly phosphorescent materials and, thus, they have been utilized as efficient phosphorescent dopants in organic light emitting diodes (OLEDs) 1–3 or as effective phosphorescent chemosensors. 4–7 Cylometalated iridium (III) complexes are chiral compounds consisting of lambda (Λ, left-handed) and delta (Δ, right-handed) isomers. Racemic cyclometa- lated iridium (III) complexes emit light with no net polarization, but optically active cyclometalated iridium (III) complexes emit circularly polarized light. 8,9 Circularly polarized light can be used in various fields including highly efficient three dimensional electronic devices, photo nic devices for optical data storage, biological assays, and others. 8,9 In order to obtain optically active cylometalated iridium (III) complexes and to determine the enantiomeric composition of optically active cylometalated iridium (III) complexes, liquid chromatogr aphic enantiomer separation method on chiral stationary phases (CSPs) has been used. For example, Okamoto and coworkers first reported the high performance liquid chromatographic (HPLC) direct enantiomeric separation of two homoleptic cylometalated iridium (III) complexes on immobilized amylose tris(3,5- dimethylphenylcarbamate) (Chiralpak IA), coated cellulose tris(3,5-dimethylphenylcarbamate) (Chiralc el OD), and coated cellulose tris(4-methylbenzoate) (Chiralce l OJ). 10 Supercritical fluid chromatography (SFC) was also used by Bernhard and coworkers for the enantiomeric separation of cylometalated iridium (III) complexes on coated amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H). 8 However, the general use of the HPLC method for the direct enantiomeric separation of homoleptic.

  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. Gas-phase infrared spectrum of phosphorus (III) oxycyanide, OPCN: experimental and theoretical investigations

    Science.gov (United States)

    Allaf, Abdul. W.; Kassem, M.; Alibrahim, M.; Boustani, Ihsan

    1999-03-01

    An attempt was made to observe the gas-phase infrared spectrum of Phosphorus (III) oxycyanide, OPCN for the first time. This molecule was produced by an on-line process using phosphorus (III) oxychloride, OPCl as precursor passed over heated AgCN. The products were characterised by the infrared spectra of their vapours. The low resolution gas-phase Fourier transform infrared spectrum shows two bands centered at 2165 and 1385 cm -1. These bands are assigned to, ν1 (CN stretch) and ν2 (OP stretch), respectively. Ab initio self-consistent-field (SCF) molecular orbital (MO) and Møller-Plesset second order perturbation theory (MP2) calculations were performed to determine the geometry, total energy and vibrational frequencies of OPCN.

  12. Gas-phase infrared spectrum of phosphorus (III) oxycyanide, OPCN: Experimental and theoretical and theoretical investigations

    International Nuclear Information System (INIS)

    Allaf, A.W.; Kassem, M.; Alibrahim, M.

    1999-01-01

    An attempt was made to observe the gas-phase infrared spectrum of phosphorus (III) oxycyanide, OPCN for the first time. This molecule was produced by on-line process using phosphorus (III) oxychloride, OPCI as precursor passed over heated Ag CN. The products were characterised by the infrared spectra of their vapours. The low resolution gas-phase Fourier transform infrared spectrum shows two bands at 2165 and 1385 cm -1 . These bands are assigned to ν 1 (C≡N stretch) and ν 2 (O=P stretch), respectively. Ab initio self-consistent-field (SCF) molecular orbital (MO) and Moeller - Plesset second order perturbation theory (MP2) calculations were performed to determine the geometry, total energy and vibrational frequencies of OPCN. (authors)

  13. Exploring the Photoreduction of Au(III) Complexes in the Gas-Phase

    Science.gov (United States)

    Marcum, Jesse C.; Kaufman, Sydney H.; Weber, J. Mathias

    2010-06-01

    We have used photodissociation spectroscopy to probe the electronic structure and photoreduction of Au(III) in gas-phase complexes containing Cl- and OH-. The gas-phase electronic spectrum of [AuCl_4]- closely resembles the aqueous solution spectrum, showing a lack of strong solvatochromic shifts. Substitution of Cl- ligands with OH- results in a strong blue shift, in agreement with ligand-field theory. Upon excitation, [AuCl_4]- can dissociate by loss of either one or two neutral Cl atoms, resulting in the reduction of gold from Au(III) to Au(II) and Au(I) respectively. The hydroxide substituted complex, [AuCl_2(OH)_2]-, demonstrates similar behavior but the only observable fragment channel is the loss of two neutral OH ligands, leading only to Au(I).

  14. Safety systems and safety analysis of the Qinshan phase III CANDU nuclear power plant

    International Nuclear Information System (INIS)

    Cai Jianping; Shen Sen; Barkman, N.

    1999-01-01

    The author introduces the Canadian nuclear reactor safety philosophy and the Qinshan Phase III CANDU NPP safety systems and safety analysis, which are designed and performed according to this philosophy. The concept of 'defence-in-depth' is a key element of the Canadian nuclear reactor safety philosophy. The design concepts of redundancy, diversity, separation, equipment qualification, quality assurance, and use of appropriate design codes and standards are adopted in the design. Four special safety systems as well as a set of reliable safety support systems are incorporated in the design of Qinshan phase III CANDU for accident mitigation. The assessment results for safety systems performance show that the fundamental safety criteria for public dose, and integrity of fuel, channels and the reactor building, are satisfied

  15. Japanese contributions to IAEA INTOR workshop, phase two A, part 2, chapter III: impurity control (engineering)

    International Nuclear Information System (INIS)

    Seki, Masahiro; Miki, Nobuharu; Shibutani, Yoji; Fujimura, Kaoru; Adachi, Jun-ichi; Sato, Kosuke; Fujii, Masaharu; Yamazaki, Seiichiro; Itoh, Shin-ichi.

    1985-07-01

    This report corresponds to the second half of Chapter III of Japanese contribution report to IAEA INTOR Workshop, Phase Two A, Part 2. Data base assessment are made on candidate materials for the divertor, limiter, and the first wall. Engineering trade-off studies are made for the high-recycling and low temperature conditions. The studies include material considerations, configuration, thermohydraulic and stress analysis, disruption, lifetime analysis, and tritium permeation. (author)

  16. The application and design of distributed control system in reactor shutdown system of Qinshan phase III

    International Nuclear Information System (INIS)

    Su Guoquan; Liu Wangtian; Yu Yijun; Xiong Weihua

    2006-03-01

    The design, commissioning and running of the reactor trip parameter monitoring system used in Qinshan Phase III are introduced. The applying technology of Distributed Control System realized trip parameter monitoring and realized the function of trip parameters quick data acquisitioning, transferring, saving, alarm, query. The applying of trip parameters monitoring system improved the abilities of plant status monitoring and event analyzing, and increased the security and economy of nuclear power plant. (authors)

  17. 200-ZP-1 phase II and III IRM groundwater pump and treat site safety plan

    International Nuclear Information System (INIS)

    St. John, C.H.

    1996-07-01

    This safety plan covers operations, maintenance, and support activities related to the 200-ZP-1 Phase II and III Ground Water Pump- and-Treat Facility. The purpose of the facility is to extract carbon tetrachloride contaminated groundwater underlying the ZP-1 Operable Unit; separate the contaminant from the groundwater; and reintroduce the treated water to the aquifer. An air stripping methodology is employed to convert volatile organics to a vapor phase for absorption onto granular activated carbon. The automated process incorporates a variety of process and safety features that shut down the process system in the event that process or safety parameters are exceeded or compromised

  18. Ultracompact electro-optic phase modulator based on III-V-on-silicon microdisk resonator.

    Science.gov (United States)

    Lloret, J; Kumar, R; Sales, S; Ramos, F; Morthier, G; Mechet, P; Spuesens, T; Van Thourhout, D; Olivier, N; Fédéli, J-M; Capmany, J

    2012-06-15

    A novel ultracompact electro-optic phase modulator based on a single 9 μm-diameter III-V microdisk resonator heterogeneously integrated on and coupled to a nanophotonic waveguide is presented. Modulation is enabled by effective index modification through carrier injection. Proof-of-concept implementation involving binary phase shift keying modulation format is assembled. A power imbalance of ∼0.6  dB between both symbols and a modulation rate up to 1.8 Gbps are demonstrated without using any special driving technique.

  19. The majority of patients with metastatic melanoma are not represented in pivotal phase III immunotherapy trials

    DEFF Research Database (Denmark)

    Donia, Marco; Kimper-Karl, Marie Louise; Høyer, Katrine Lundby

    2017-01-01

    BACKGROUND: Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of 'real-world' patients diag...... a huge knowledge gap regarding the usefulness of new immunotherapies in the 'real-world' patient population, and urge additional testing of known regimens in selected poor prognosis cohorts.......BACKGROUND: Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of 'real-world' patients...... in 2014, were included in the analysis. Seven pre-defined eligibility criteria, all used to select patients for enrolment in five recent randomised phase III immunotherapy trials, were analysed. RESULTS: Fifty-five percent of the total population with MM did not meet one or more eligibility criteria ('not...

  20. Conceptual design report for environmental, safety and health phase III FY-91 line item

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1988-09-01

    The Mound Facility (Mound), located in Miamisburg, Ohio, is a Department of Energy (DOE) development and production facility performing support work for DOE`s weapons and energy-related programs. EG&G Mound Applied Technologies (EG&G) is the Operating Contractor (OC) for this Government-Owned, Contractor-Operated (GOCO) facility. The work performed at Mound emphasizes nuclear energy and explosives technology. Mound is currently implementing an Environmental, Safety, and Health (ES&H) Program designed to protect its employees, the public, and the environment from adverse effects caused by the facility`s activities. Design has been completed, and construction is in progress for Phase I of this multiphase program. Phase II has been submitted for fiscal year (FY) 89 funding and Phase IV is being submitted as an FY 92 line item. This Conceptual Design Report (CDR) addresses Phase III of the ES&H program.

  1. Preparation and thermal properties of Glauber’s salt-based phase-change materials for Qinghai-Tibet Plateau solar greenhouses

    Science.gov (United States)

    Jiang, Zipeng; Tie, Shengnian

    2017-07-01

    This paper reports the preparation and characterization of eutectic Glauber’s salt-based composite, phase-change materials (G-PCMs). PCMs were prepared using industrial-grade sodium sulfate decahydrate (Na2SO4 ṡ 10H2O) as the basic material. Other salts were added to obtain the eutectic Glauber’s salt-based PCMs with phase-change temperatures of 25∘C, 15∘C and 10∘C. The modification of the G-PCMs was designed using the same experimental method to select the efficient nucleating, thickening and thermal conductive agents. The results show that borax can be an effective nucleating agent, sodium carboxymethyl cellulose is an excellent thickener and carbon powder is a good thermal conductive agent. The phase-change temperature, latent heat and thermal conductivity of the three different PCMs are 23.9∘C, 15.4∘C and 9.5∘C; 179.6, 129 and 116.2 J/g; and 1.02, 1.10 and 1.23 W/(m K), respectively. These PCMs possess suitable phase-change temperature, high latent heat and good thermal conductivity, and can be used in Qinghai-Tibet Plateau agricultural solar greenhouses.

  2. Controls on magma permeability in the volcanic conduit during the climactic phase of the Kos Plateau Tuff eruption (Aegean Arc)

    Science.gov (United States)

    Degruyter, W.; Bachmann, O.; Burgisser, A.

    2010-01-01

    X-ray computed microtomography (µCT) was applied to pumices from the largest Quaternary explosive eruption of the active South Aegean Arc (the Kos Plateau Tuff; KPT) in order to better understand magma permeability within volcanic conduits. Two different types of pumices (one with highly elongated bubbles, tube pumice; and the other with near spherical bubbles, frothy pumice) produced synchronously and with identical chemical composition were selected for µCT imaging to obtain porosity, tortuosity, bubble size and throat size distributions. Tortuosity drops on average from 2.2 in frothy pumice to 1.5 in tube pumice. Bubble size and throat size distributions provide estimates for mean bubble size (~93-98 μm) and mean throat size (~23-29 μm). Using a modified Kozeny-Carman equation, variations in porosity, tortuosity, and throat size observed in KPT pumices explain the spread found in laboratory measurements of the Darcian permeability. Measured difference in inertial permeability between tube and frothy pumices can also be partly explained by the same variables but require an additional parameter related to the internal roughness of the porous medium (friction factor f 0 ). Constitutive equations for both types of permeability allow the quantification of laminar and turbulent gas escape during ascent of rhyolitic magma in volcanic conduits.

  3. Phase II and III the next generation of CLS beamline control and data acquisition systems

    International Nuclear Information System (INIS)

    Matias, E.; Beauregard, D.; Berg, R.; Black, G.; Boots, M.J.; Dolton, W.; Hunter, D.; Igarashi, R.; Liu, D.; Maxwell, D.; Miller, C.D.; Wilson, T.; Wright, G.

    2012-01-01

    The Canadian Light Source (CLS) is nearing the completion of its suite of Phase II Beamlines and in detailed design of its Phase III Beamlines. The paper presents an overview of the overall approach adopted by CLS in the development of beamline control and data acquisition systems. Building on the experience of our first phase of beamlines the CLS has continued to make extensive use of EPICS with EDM and QT based user interfaces. Increasing interpretive languages such as Python are finding a place in the beamline control systems. Web based environment such as ScienceStudio have also found a prominent place in the control system architecture as we move to tighter integration between data acquisition, visualization and data analysis. (authors)

  4. Contributions to reversed-phase column selectivity: III. Column hydrogen-bond basicity.

    Science.gov (United States)

    Carr, P W; Dolan, J W; Dorsey, J G; Snyder, L R; Kirkland, J J

    2015-05-22

    Column selectivity in reversed-phase chromatography (RPC) can be described in terms of the hydrophobic-subtraction model, which recognizes five solute-column interactions that together determine solute retention and column selectivity: hydrophobic, steric, hydrogen bonding of an acceptor solute (i.e., a hydrogen-bond base) by a stationary-phase donor group (i.e., a silanol), hydrogen bonding of a donor solute (e.g., a carboxylic acid) by a stationary-phase acceptor group, and ionic. Of these five interactions, hydrogen bonding between donor solutes (acids) and stationary-phase acceptor groups is the least well understood; the present study aims at resolving this uncertainty, so far as possible. Previous work suggests that there are three distinct stationary-phase sites for hydrogen-bond interaction with carboxylic acids, which we will refer to as column basicity I, II, and III. All RPC columns exhibit a selective retention of carboxylic acids (column basicity I) in varying degree. This now appears to involve an interaction of the solute with a pair of vicinal silanols in the stationary phase. For some type-A columns, an additional basic site (column basicity II) is similar to that for column basicity I in primarily affecting the retention of carboxylic acids. The latter site appears to be associated with metal contamination of the silica. Finally, for embedded-polar-group (EPG) columns, the polar group can serve as a proton acceptor (column basicity III) for acids, phenols, and other donor solutes. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Imprinted magnetic graphene oxide for the mini-solid phase extraction of Eu (III) from coal mine area

    Science.gov (United States)

    Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K.

    2017-05-01

    The present work represents the preparation of imprinted magnetic reduced graphene oxide and applied it for the selective removal of Eu (III) from local coal mines area. A simple solid phase extraction method was used for this purpose. The material shows a very high adsorption as well as removal efficiency towards Eu (III), which suggest that the material have potential to be used in future for their real time applications in removal of Eu (III) from complex matrices.

  6. A new ion imprinted polymer based on Ru(III)-thiobarbituric acid complex for solid phase extraction of ruthenium(III) prior to its determination by ETAAS

    International Nuclear Information System (INIS)

    Zambrzycka, Elżbieta; Godlewska-Żyłkiewicz, Beata

    2014-01-01

    A new ruthenium ion imprinted polymer was prepared from the Ru(III) 2-thiobarbituric acid complex (the template), methacrylic acid or acrylamide (the functional monomers), and ethylene glycol dimethacrylate (the cross-linking agent) using 2,2′-azobisisobutyronitrile as the radical initiator. The ion imprinted polymer was characterized and used as a selective sorbent for the solid phase extraction of Ru(III) ions. The effects of type of functional monomer, sample volume, solution pH and flow rate on the extraction efficiency were studied in the dynamic mode. Ru(III) ion was quantitatively retained on the sorbents in the pH range from 3.5 to 10, and can be eluted with 4 mol L−1 aqueous ammonia. The affinity of Ru(III) for the ion imprinted polymer based on the acrylamide monomer is weaker than that for the polymer based on the methacrylic acid monomer, which therefore was used in interference studies and in analytical applications. Following extraction of Ru(III) ions with the imprint and their subsequent elution from the polymer with aqueous ammonia, Ru(III) was detected by electrothermal atomic absorption spectrometry with a detection limit of 0.21 ng mL −1 . The method was successfully applied to the determination of trace amounts of Ru(III) in water, waste, road dust and platinum ore (CRM SARM 76) with a reproducibility (expressed as RSD) below 6.4 %. (author)

  7. An Application of Graphical Approach to Construct Multiple Testing Procedure in a Hypothetical Phase III Design

    Directory of Open Access Journals (Sweden)

    Naitee eTing

    2014-01-01

    Full Text Available Many multiple testing procedures (MTP have been developed in recent years. Among these new procedures, the graphical approach is flexible and easy to communicate with non-statisticians. A hypothetical Phase III clinical trial design is introduced in this manuscript to demonstrate how graphical approach can be applied in clinical product development. In this design, an active comparator is used. It is thought that this test drug under development could potentially be superior to this comparator. For comparison of efficacy, the primary endpoint is well established and widely accepted by regulatory agencies. However, an important secondary endpoint based on Phase II findings looks very promising. The target dose may have a good opportunity to deliver superiority to the comparator. Furthermore, a lower dose is included in case the target dose may demonstrate potential safety concerns. This Phase III study is designed as a non-inferiority trial with two doses, and two endpoints. This manuscript will illustrate how graphical approach is applied to this design in handling multiple testing issues.

  8. Development of a central data warehouse for statewide ITS and transportation data in Florida phase III : final report.

    Science.gov (United States)

    2009-12-15

    This report documents Phase III of the development and operation of a prototype for the Statewide Transportation : Engineering Warehouse for Archived Regional Data (STEWARD). It reflects the progress on the development and : operation of STEWARD sinc...

  9. On the determination of Zr(IV), Ce((III), Th(IV) and U(VI) in organic phase using arsenazo-I and arsenazo-III

    International Nuclear Information System (INIS)

    El-Sweify, F.H.; Kamel, M.M.; Shabana, R.

    1997-01-01

    Some organic extractants of different types, namely tridodecylamine (TDA), tricapryl methyl ammonium chloride (TCMA), di(2-ethylhexyl) phosphoric acid (HDEHP) and 1-[thenoyl-(2)]-3,3,3-trifluoroacetone (HTTA) in xylene have been used to study the extraction behaviour of coloured complexes of Zr(IV), Ce(III), Th(IV) and U(VI) from slightly acidic aqueous solutions of arsenazo-III. Spectrophotometric study for the determination of the aforementioned elements, as well as the colouring agents arsenazo-I and arsenazo-III in the organic phase has been carried out. Some factors affecting the spectrophotometric determination of these elements were studied. These factors were hydrogen ion concentration, concentration of the colouring agents in the aqueous phase and diluent type. Absorption spectra and standard curves are given. The molar extinction coefficients have been calculated. 10 figs

  10. Superior outcome of women with stage I/II cutaneous melanoma: Pooled analysis of four European organisation for research and treatment of cancer phase III trials

    NARCIS (Netherlands)

    A. Joosse (Arjen); S. Collette (Sandra); S. Suciu (Stefan); T.E.C. Nijsten (Tamar); F.J. Lejeune (Ferdy); U.R. Kleeberg (Ulrich); J.W.W. Coebergh (Jan Willem); A.M.M. Eggermont (Alexander); E.G.E. de Vries (Elisabeth)

    2012-01-01

    textabstractPurpose: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for

  11. Clinical effects of Angelica dahurica dressing on patients with I-II phase pressure sores.

    Science.gov (United States)

    Gong, Fen; Niu, Junzhi; Pei, Xing

    2016-11-02

    Angelica dahurica is a well-known traditional Chinese Medicine (TCM), while little information is available about its effects on pressure sores. We aimed to investigate the clinical effect of Angelica dahurica on patients with I-II phase pressure sores, as well as the underlying mechanism. Patients (n = 98) with phase I and phase II pressure sores were enrolled and randomly assigned to control and treated groups. In addition to holistic nursing, patients in the control group received compound clotrimazole cream, while patients in the treated group received continuous 4 weeks of external application of Angelica dahurica dressing. Therapeutic effect was recorded, along with the levels of interleukin-8 (IL-8), epidermal growth factor (EGF), transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF). Besides, HaCaT cells were cultured with different concentrations of Angelica dahurica, and then cell viability, clone formation numbers, cell cycle, and levels of cyclin D1 and cyclin-dependent kinase (CDK) 2 were determined. The total effective rate in the treated group was significantly higher than in the control group. Levels of IL-8, EGF, TGF-β, and VEGF were statistically increased by Angelica dahurica. In addition, the cell viability and clone formation numbers were significantly upregulated by Angelica dahurica in a dose-dependent manner. Also, the percentage of cells in G0/G1 phase, and levels of cyclin D1 and CDK2 were significantly elevated. Our results suggest that Angelica dahurica may provide an effective clinical treatment for I-II phase pressure sores.

  12. INL Results for Phases I and III of the OECD/NEA MHTGR-350 Benchmark

    Energy Technology Data Exchange (ETDEWEB)

    Gerhard Strydom; Javier Ortensi; Sonat Sen; Hans Hammer

    2013-09-01

    The Idaho National Laboratory (INL) Very High Temperature Reactor (VHTR) Technology Development Office (TDO) Methods Core Simulation group led the construction of the Organization for Economic Cooperation and Development (OECD) Modular High Temperature Reactor (MHTGR) 350 MW benchmark for comparing and evaluating prismatic VHTR analysis codes. The benchmark is sponsored by the OECD's Nuclear Energy Agency (NEA), and the project will yield a set of reference steady-state, transient, and lattice depletion problems that can be used by the Department of Energy (DOE), the Nuclear Regulatory Commission (NRC), and vendors to assess their code suits. The Methods group is responsible for defining the benchmark specifications, leading the data collection and comparison activities, and chairing the annual technical workshops. This report summarizes the latest INL results for Phase I (steady state) and Phase III (lattice depletion) of the benchmark. The INSTANT, Pronghorn and RattleSnake codes were used for the standalone core neutronics modeling of Exercise 1, and the results obtained from these codes are compared in Section 4. Exercise 2 of Phase I requires the standalone steady-state thermal fluids modeling of the MHTGR-350 design, and the results for the systems code RELAP5-3D are discussed in Section 5. The coupled neutronics and thermal fluids steady-state solution for Exercise 3 are reported in Section 6, utilizing the newly developed Parallel and Highly Innovative Simulation for INL Code System (PHISICS)/RELAP5-3D code suit. Finally, the lattice depletion models and results obtained for Phase III are compared in Section 7. The MHTGR-350 benchmark proved to be a challenging simulation set of problems to model accurately, and even with the simplifications introduced in the benchmark specification this activity is an important step in the code-to-code verification of modern prismatic VHTR codes. A final OECD/NEA comparison report will compare the Phase I and III

  13. Single-crystal neutron diffraction study of ammonium nitrate phase III

    International Nuclear Information System (INIS)

    Choi, C.S.; Prask, H.J.

    1982-01-01

    The crystal structure of ammonium nitrate phase III has been studied at room temperature by neutron diffraction using a single crystal containing 5% KNO 3 in solid-solution form. The space group is Pnma, with a = 7.6772 (4), b = 5.8208 (4), c = 7.1396 (5) A, Z = 4. The final residual after full-matrix least-squares refinement was R = 0.042 for 348 observed reflections. The ammonium ions are thermally disordered into two orientations, displaced by an angle of approximately 42 0 about an axis parallel to the c axis. (Auth.)

  14. SAFOD Phase III Core Sampling and Data Management at the Gulf Coast Repository

    Directory of Open Access Journals (Sweden)

    David Lockner

    2011-03-01

    Full Text Available The San Andreas Fault Observatory at Depth (SAFODproject is yielding new insight into the San Andreas Fault (Zoback et al., 2010; Zoback et al., this issue. SAFOD drilling started in 2002 with a pilot hole, and proceeded with three phrases of drilling and coring during the summers of 2004, 2005, and 2007 (Fig. 1. One key component of theproject is curation, sampling, and documentation of SAFOD core usage at the Integrated Ocean Drilling Program’s (IODP Gulf Coast Repository (GCR at Texas A&M University. We present here the milestones accomplished over the past two years of sampling Phase III core at the GCR.

  15. Investor Outlook: Focus on Upcoming LCA2 Gene Therapy Phase III Results.

    Science.gov (United States)

    Schimmer, Joshua; Breazzano, Steven

    2015-09-01

    Investor interest in gene therapy has increased substantially over the past few years, and the next major catalyst for the field is likely to be Spark Therapeutics's phase III trial for 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). Analysis of the approach from the basic genetics, underlying visual mechanisms, clinical data, and commercialization considerations helps frame investor expectations and the potential implications for the broader field.

  16. Stability considerations of permanent magnet quadrupoles for CESR phase-III upgrade

    Directory of Open Access Journals (Sweden)

    W. Lou

    1998-06-01

    Full Text Available The Cornell electron storage ring (CESR phase-III upgrade plan includes very strong permanent magnet quadrupoles in front of the cryostat for the superconducting quadrupoles and physically as close as possible to the interaction point. Together with the superconducting quadrupoles, they provide tighter vertical focusing at the interaction point. The quadrupoles are built with neodymium iron boron (NdFeB material and operate inside the 15 kG solenoid field. Requirements on the field quality and stability of these quadrupoles are discussed and test results are presented.

  17. Enginnering development of coal-fired high performance power systems phase II and III

    International Nuclear Information System (INIS)

    1998-01-01

    This report presents work carried out under contract DE-AC22-95PC95144 ''Engineering Development of Coal-Fired High Performance Systems Phase II and III.'' The goals of the program are to develop a coal-fired high performance power generation system (HIPPS) that is capable of: thermal efficiency (HHV) >47%; NOx, SOx, and particulates 65% of heat input; all solid wastes benign; cost of electricity <90% of present plants. Phase I, which began in 1992, focused on the analysis of various configurations of indirectly fired cycles and on technical assessments of alternative plant subsystems and components, including performance requirements, developmental status, design options, complexity and reliability, and capital and operating costs. Phase I also included preliminary R ampersand D and the preparation of designs for HIPPS commercial plants approximately 300 MWe in size. This phase, Phase II, involves the development and testing of plant subsystems, refinement and updating of the HIPPS commercial plant design, and the site selection and engineering design of a HIPPS prototype plant. Work reported herein is from: Task 2.2 HITAF Air Heaters; Task 6 HIPPS Commercial Plant Design Update

  18. 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

  19. Evaluation of candidate magnetohydrodynamic materials for the U-02 Phase III test

    International Nuclear Information System (INIS)

    Marchant, D.D.; Bates, J.L.

    1978-06-01

    As part of a cooperative U.S.--U.S.S.R. program, electrode and insulator materials tested at the Westinghouse Electrode Systems Test Facility in Pittsburgh, Pennsylvania, were evaluated. From this evaluation materials will be selected for use in the third phase of tests being conducted in the U-02 magnetohydrodynamics test facility in the Soviet Union. Electrode and insulator materials were examined with both an optical microscope and a scanning electron microscope. The cathodes were found to behave differently from the anodes; most notably, the cathodes showed greater potassium interaction. The lanthanum chromite-based electrodes (excluding those fabricated by plasma-spraying) are recommended for testing in the U-02 Phase III test. Hotpressed, fused-grained MgO and sintered MgAl 2 O 4 are recommended as insulator materials. The electrode attachment techniques used in the Westinghouse Tests were inadequate and need to be modified for the U-02 test

  20. The third phase of the OECD/NEA TDB project: TDB III

    International Nuclear Information System (INIS)

    Mompean, F.J.; Illemassene, M.; Perrone, J.

    2005-01-01

    In 2003 with a foreseen duration of four years. The main objective of this new phase is to extend the existing critically reviewed database for elements of relevance in radioactive waste management, paying attention to the needs of the various national programmes. Following the decision by the Project Management Board (integrated by representatives of 16 organisations with responsibilities in radioactive waste management in 12 OECD member countries) the elements contemplated in this new phase are Th, Sn and Fe, with a higher priority being allocated to inorganic species and compounds. In addition to the corresponding review teams for these elements, an additional expert team has been constituted to prepare guidelines for the evaluation of thermodynamic data for solid solutions. As was the case in TDB Phase II, the basic project review methodology remains unaltered in TDB III. The Figure illustrates the relationship between the various TDB bodies, with an International Organisation, the OECD NEA, acting as Project Coordinator and linking the independent scientific teams and the project governing bodies. This organizational paradigm has proven successful with the recent completion of the five Phase II Reviews (Update, Ni, Se, Zr and Organic Ligands). The review and expert team activities were started in 2004 (except for Fe, being started in 2005) following an initiation stage. This preliminary stage was designed in order to tailor the team compositions to the existing literature for each element. The first reviews stemming from TDB III are scheduled to appear in published form in 2007. The successful completion of these objectives will add three further reports to the current series of nine volumes (dealing with the chemical thermodynamics of U, Np, Pu, Am, Tc, Ni, Se, Zr and compounds and complexes of these elements with oxalate, citrate, EDTA and isa). (authors)

  1. DECOVALEX - Mathematical models of coupled T-H-M processes for nuclear waste repositories. Report of phase III

    International Nuclear Information System (INIS)

    Jing, L.; Rutqvist, J.; Stephansson, O.

    1995-12-01

    This report presents the methodologies and results of the field/laboratory experiments and mathematical modeling defined for the phase III of the project. Results from test cases 2-6 are given in separate chapters of the report (which have been indexed separately), and the last chapter discusses the lessons learned from the three phases of the DECOVALEX project

  2. Inhibition of X-ray-induced potentially lethal damage (PLD) repair in aerobic plateau-phase Chinese hamster cells by misonidazole

    International Nuclear Information System (INIS)

    Brown, D.M.

    1984-01-01

    The effect of the 2-nitroimidazole radiosensitizer misonidazole (MISO) and the hydrophilic analog SR-2508 on the repair of X-ray-induced potentially lethal damage (PLD) was studied in plateau-phase Chinese Hamster ovary (HA-1) cells. It was found that although MISO does not radiosensitize aerobic cells, it inhibits the repair of PLD. However, under hypoxic conditions, MISO has no effect on PLD repair. The major portion of the inhibition of PLD repair in aerobic cells requires the presence of MISO only during irradiation; little or no additional inhibition occurs when MISO is present during the postirradiation repair period. Also, treatment of aerobic cells with 5 mM MISO for either 5 or 30 min prior to irradiation is equally inhibitory. This suggests that the presence of MISO in some way modifies the initial lesion under aerobic conditions since it does not increase cell killing as determined by immediate plating but inhibits subsequent repair. The inhibition is concentration dependent; 0.5 mM MISO inhibits PLD repair by one-half while 5-10 mM totally inhibits the repair measured 6 hr postirradiation. This phenomenon suggests that radiosensitization of tissue in vivo by MISO and other 2-nitroimidazoles may not be unequivocal proof of the presence of hypoxic cells

  3. Patterns of cell loss and repopulation in irradiated cultures of plateau phase C3H 10T1/2 cells

    International Nuclear Information System (INIS)

    Zeman, E.M.; Bedford, J.S.

    1985-01-01

    Patterns of cell loss and repopulation were studied in plateau phase cultures of slowly-cycling, contact-inhibited C3H 10T1/2 mouse fibroblasts following large single, and multiple small doses 137 Cs-gamma rays. A progressive, dose-independent cell loss was apparent within after irradiation with large single doses, and similar patterns of loss were observed following the start of multifraction irradiations. This progressive cell loss culminated in the loss of integrity of the monolayer of cells, a loss of contact-inhibition, and therefore, an increased rate of cell division. Repopulation did not start immediately after the start of irradiation, but needed a triggering event, in this case, a decrease to a critical level in the cell density. Once initiated, repopulation was able to decrease or even eliminate the effectiveness of subsequent doses in reducing the number of viable cells per culture. To the extent that the responses of slowly-cycling, contact-inhibited cells in vitro can be applied to interpret the radiation responses of cell populations in vivo, these results further support the notion that it may be necessary, in some cases, to account for an increasing contribution from repopulation with increasing overall treatment time in dose fractionation isoeffect formulae used for predicting tissue tolerances or tumor control. (Auth.)

  4. Interaction between x-irradiated plateau-phase bone marrow stromal cell lines and co-cultivated factor-dependent cell lines leading to leukemogenesis in vitro

    International Nuclear Information System (INIS)

    Naparstek, E.; Anklesaria, P.; FitzGerald, T.J.; Sakakeeny, M.A.; Greenberger, J.S.

    1987-01-01

    Plateau-phase mouse clonal bone marrow stromal cell lines D2XRII and C3H cl 11 produce decreasing levels of M-CSF (CSF-1), a specific macrophage progenitor cell humoral regulator, following X-irradiation in vitro. The decrease did not go below 40% of control levels, even after irradiation doses of 50,000 rad (500 Gy). In contrast, a distinct humoral regulator stimulating growth of GM-CSF/IL-3 factor-dependent (FD) hematopoietic progenitor cell lines was detected following radiation to doses above 2000 rad. This humoral factor was not detectable in conditioned medium from irradiated cells, weakly detected using factor-dependent target cell populations in agar overlay, and was prominently detected by liquid co-cultivation of factor-dependent cells with irradiated stromal cell cultures. Subclonal lines of FD cells, derived after co-cultivation revealed karyotypic abnormalities and induced myeloblastic tumors in syngeneic mice. Five-eight weeks co-cultivation was required for induction of factor independence and malignancy and was associated with dense cell to cell contact between FD cells and stromal cells demonstrated by light and electron microscopy. Increases in hematopoietic to stromal cell surface area, total number of adherent cells per flask, total non-adherent cell colonies per flask, and cumulative non-adherent cell production were observed after irradiation. The present data may prove very relevant to an understanding of the cell to cell interactions during X-irradiation-induced leukemia

  5. Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials.

    Science.gov (United States)

    Plennevaux, Eric; Moureau, Annick; Arredondo-García, José L; Villar, Luis; Pitisuttithum, Punnee; Tran, Ngoc H; Bonaparte, Matthew; Chansinghakul, Danaya; Coronel, Diana L; L'Azou, Maïna; Ochiai, R Leon; Toh, Myew-Ling; Noriega, Fernando; Bouckenooghe, Alain

    2018-04-03

    We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. NCT01373281 and NCT01374516.

  6. Objective Lightning Probability Forecasting for Kennedy Space Center and Cape Canaveral Air Force Station, Phase III

    Science.gov (United States)

    Crawford, Winifred C.

    2010-01-01

    The AMU created new logistic regression equations in an effort to increase the skill of the Objective Lightning Forecast Tool developed in Phase II (Lambert 2007). One equation was created for each of five sub-seasons based on the daily lightning climatology instead of by month as was done in Phase II. The assumption was that these equations would capture the physical attributes that contribute to thunderstorm formation more so than monthly equations. However, the SS values in Section 5.3.2 showed that the Phase III equations had worse skill than the Phase II equations and, therefore, will not be transitioned into operations. The current Objective Lightning Forecast Tool developed in Phase II will continue to be used operationally in MIDDS. Three warm seasons were added to the Phase II dataset to increase the POR from 17 to 20 years (1989-2008), and data for October were included since the daily climatology showed lightning occurrence extending into that month. None of the three methods tested to determine the start of the subseason in each individual year were able to discern the start dates with consistent accuracy. Therefore, the start dates were determined by the daily climatology shown in Figure 10 and were the same in every year. The procedures used to create the predictors and develop the equations were identical to those in Phase II. The equations were made up of one to three predictors. TI and the flow regime probabilities were the top predictors followed by 1-day persistence, then VT and Ll. Each equation outperformed four other forecast methods by 7-57% using the verification dataset, but the new equations were outperformed by the Phase II equations in every sub-season. The reason for the degradation may be due to the fact that the same sub-season start dates were used in every year. It is likely there was overlap of sub-season days at the beginning and end of each defined sub-season in each individual year, which could very well affect equation

  7. Evidence that progression of cells into S-phase is not a prerequisite for recovery between split doses of U.V.-light in synchronized and plateau phase cultures of Ehrlich ascites tumour cells

    International Nuclear Information System (INIS)

    Iliakis, G.; Nuesse, M.

    1982-01-01

    The ability of Ehrlich ascites tumour cells (EAT-cells) to perform split-dose recovery after U.V. exposure was studied with unfed plateau phase as well as with synchronized cells selected from exponentially growing cultures. The cells were kept in balanced salt solution which inhibited the progression of the cells through the cell cycle. The results indicated that split-dose recovery occurred in EAT-cells in all phases of the cell cycle and that progression of the cells into S-phase was not a prerequisite for this type of repair. The second-dose survival curves of G 1 -and S-phase cells showed, 24 hours after the first U.V. exposure, a shoulder width comparable to that of singly irradiated cells. Second-dose survival curves for G 2 -cells showed, after the same time interval, a shoulder width smaller than that for singly exposed cells, presumably due to some cell division. The recovery time constant (t 50 between 4 and 8 hours) increased with increasing U.V. exposure. (author)

  8. The Phase I/II BNCT Trials at the Brookhaven medical research reactor: Critical considerations

    International Nuclear Information System (INIS)

    Diaz, A.Z.

    2001-01-01

    A phase I/II clinical trial of boronophenylalanine-fructose (BPA-F) mediated boron neutron capture therapy (BNCT) for Glioblastoma Multiforme (GBM) was initiated at Brookhaven National Laboratory (BNL) in 1994. Many critical issues were considered during the design of the first of many sequential dose escalation protocols. These critical issues included patient selection criteria, boron delivery agent, dose limits to the normal brain, dose escalation schemes for both neutron exposure and boron dose, and fractionation. As the clinical protocols progressed and evaluation of the tolerance of the central nervous system (CNS) to BPA-mediated BNCT at the BMRR continued new specifications were adopted. Clinical data reflecting the progression of the protocols will be presented to illustrate the steps taken and the reasons behind their adoption. (author)

  9. 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.

  10. Runaway electron damage to the Tore Supra Phase III outboard pump limiter

    International Nuclear Information System (INIS)

    Nygren, R.; Lutz, T.; Walsh, D.; Martin, G.; Chatelier, M.; Loarer, T.; Guilhem, D.

    1996-01-01

    Operation of the Phase III outboard pump limiter (OPL) in Tore Supra in 1994 was terminated prematurely when runaway electrons during the current decay following a disruption pierced leading edge tube on the electron side and caused a water leak. The location, about 20 mm outside the last closed flux surface during normal operation, and the infrared (IR) images of the limiter indicate that the runaways moved in large outward steps, i.e. tens of millimeters, in one toroidal revolution. For plasma (runaway) currents in the range of 155 to 250 kA, the drift orbits open to the outside. Basic trajectory computations suggest that such motion is possible under the conditions present for this experiment. Activation measurements made on sections of the tube to indicate the area of local damage are presented here. An understanding of this event may provide important guidance regarding the potential damage from runaways in future tokamaks

  11. Production circulator fabrication and testing for core flow test loop. Final report, Phase III

    Energy Technology Data Exchange (ETDEWEB)

    1981-05-01

    The performance testing of two production helium circulators utilizing gas film lubrication is described. These two centrifugal-type circulators plus an identical circulator prototype will be arranged in series to provide the helium flow requirements for the Core Flow Test Loop which is part of the Gas-Cooled Fast Breeder Reactor Program (GCFR) at the Oak Ridge National Laboratory. This report presents the results of the Phase III performance and supplemental tests, which were carried out by MTI during the period of December 18, 1980 through March 19, 1981. Specific test procedures are outlined and described, as are individual tests for measuring the performance of the circulators. Test data and run descriptions are presented.

  12. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis

    DEFF Research Database (Denmark)

    Vollmer, T L; Sorensen, P S; Selmaj, K

    2014-01-01

    The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex(®) reference arm). RRMS patients age 18-55 years with Expanded Disability Status Scale (EDSS) scores...... months. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included percent brain volume change (PBVC) and 3-month confirmed disability worsening. In all, 1,331 patients were randomized: laquinimod (n = 434), placebo (n = 450), and IFNβ-1a (n = 447). ARR was not significantly...... reduced with laquinimod [-18 %, risk ratio (RR) = 0.82, 95 % CI 0.66-1.02; p = 0.075] vs. placebo. Laquinimod significantly reduced PBVC (28 %, p change in confirmed disability worsening with laquinimod measured...

  13. Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials

    DEFF Research Database (Denmark)

    Barbour, S; Smit, T.; Wang, X

    2017-01-01

    adverse events by use versus non-use of drug substrates of CYP2D6 or BCRP. Patients and methods: Patients were randomized to receive either 180 mg oral rolapitant or placebo approximately 1-2 hours before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data...... cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined...... for treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overall population and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. Results: In the integrated safety population, 828...

  14. Production circulator fabrication and testing for core flow test loop. Final report, Phase III

    International Nuclear Information System (INIS)

    1981-05-01

    The performance testing of two production helium circulators utilizing gas film lubrication is described. These two centrifugal-type circulators plus an identical circulator prototype will be arranged in series to provide the helium flow requirements for the Core Flow Test Loop which is part of the Gas-Cooled Fast Breeder Reactor Program (GCFR) at the Oak Ridge National Laboratory. This report presents the results of the Phase III performance and supplemental tests, which were carried out by MTI during the period of December 18, 1980 through March 19, 1981. Specific test procedures are outlined and described, as are individual tests for measuring the performance of the circulators. Test data and run descriptions are presented

  15. Direct disposal of spent fuel. Simulation of shaft transport. Phase III. Final report

    International Nuclear Information System (INIS)

    Filbert, W.; Heda, M.; Khamis, M.; Neydek, J.; Niehues, N.; Rissel, J.; Schrimpf, C.; Weber, W.; Fuchs, D.; Gerlach, A.; Langebrake, F.; Sindern, W.; Gasch, A.; Leicht, R.; Schwab, B.; Hecke, R. van; Kipka, P.; Simmich, K.; Weber, H.

    1994-01-01

    The aim of these demonstration tests was to verify the technical feasibility of a shaft hoisting equipment with a payload of 85 t as well as the safe transport of POLLUX-casks. In phase III of the project the components and the test stand were built, their proper functioning and reliability were tested to demonstrate that they are state-of-the-art. The following additional investigations were carried out: - Tests to fix operational disturbances and simulation tests for the new components to demonstrate their licensibility -Selection and lifetime tests of ropes and investigation of the present state-of-the-art of rope slighting under the conditions of the conceptual design of the shaft hoisting facility - Execution of a probabilistic safety analysis e.g. the determination of the release of radioactive material (result: probability [de

  16. The Qinshan phase III project-a successful model of sino-canadian cooperation

    International Nuclear Information System (INIS)

    Pang, S.H.H.; Alikhan, S.; Gu Jun

    2005-01-01

    The Qinshan Phase III (CANDU) Project, the largest-scale cooperative project between China and Canada, was completed in 2003 well in advance of the schedule and 10% under budget. The Third Qinshan (Phase III) Nuclear Power Plant (TQNPP) was built in record times: Unit 1 achieved commercial operation on December 31, 2002 and Unit 2 on July 20, 2003, 43 days and 115 days ahead of schedule respectively. Improvements in design and construction methods allowed Unit 1 to be constructed in 51.5 months from First Concrete to Criticality - a record in China for nuclear power plants. The key factors are project management and project management tools, quality assurance, construction methods, electronic documentation with configuration control that provides up-to-date on-line information, CADDS design linked with material management and control. New design and construction techniques were introduced by combining conventional AECL practices with working experiences in China. The most advanced tools and techniques for achieving optimum construction quality, schedule and cost were used. Successful application of advanced project management methods and tools has benefited TQNPC in its subsequent plant operation, and the Chinese contractors in advancing their capabilities in future nuclear projects in China as well as enhancing their opportunities internationally. Excellent co-operation and teamwork within the integrated TQNPC/AECL Commissioning Team with well documented QA program, process and procedures also contributed to the remarkable success of the Project. AECL's initial assessment, based on lessons learned, showed that the project schedule could readily be reduced to 66 months and the capital costs reduced by 25% for a replication project. AECL is building on this experience and successful results of TQNPP in its Advanced CANDU Reactor TM (ACR TM ) ** design. (authors)

  17. Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer

    International Nuclear Information System (INIS)

    Inoue, Takehiro; Inoue, Toshihiko; Teshima, Teruki; Murayama, Shigeyuki; Shimizutani, Kimishige; Fuchihata, Hajime; Furukawa, Souhei

    1996-01-01

    Purpose: Oral tongue carcinomas are highly curable with radiotherapy. In the past, patients with tongue carcinoma have usually been treated with low dose rate (LDR) interstitial radiation. This Phase III study was designed to compare the treatment results obtained with LDR with those obtained with high dose rate (HDR) interstitial radiotherapy for tongue carcinoma. Methods and Materials: The criteria for patient selection for the Phase III study were: (a) presence of a T1T2N0 tumor that could be treated with single-plane implantation, (b) localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm or less, (d) performance status between O and 3, and (e) absence of any severe concurrent disease. From April 1992 through December 1993, 15 patients in the LDR group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6 days) were accrued. The time interval between two fractions of the HDR brachytherapy was more than 6 h. Results: Local recurrence occurred in two patients treated with LDR brachytherapy but in none of the patients treated with HDR. One- and 2-year local control rates for patients in the LDR group were both 86%, compared with 100% in the HDR group (p = 0.157). There were four patients with nodal metastasis in the LDR group and three in the HDR group. Local recurrence occurred in two of the four patients with nodal metastases in the LDR group. One- and 2-year nodal control rates for patients in the LDR group are were 85%, compared with 79% in the HDR group. Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs

  18. Evaluating Intermittent Androgen-Deprivation Therapy Phase III Clinical Trials: The Devil Is in the Details.

    Science.gov (United States)

    Hussain, Maha; Tangen, Catherine; Higano, Celestia; Vogelzang, Nicholas; Thompson, Ian

    2016-01-20

    Intermittent androgen deprivation (IAD) has been widely tested in prostate cancer. However, phase III trials testing continuous androgen deprivation (CAD) versus IAD have reached inconclusive and seemingly contradictory results. Different design and conduct issues must be critically evaluated to better interpret the results. Seven published phase III trials were examined for prespecified design and outcomes. Treatment specifications; primary end point; superiority versus noninferiority design assumptions, including magnitude of assumed versus observed noninferiority margin (NIM); duration of follow-up; and quality-of-life (QOL) outcomes were considered in terms of the results and conclusions reported. Five trials had a superiority and three had a noninferiority primary hypothesis. Only three trials had a uniform population and overall survival (OS) end point. All trials observed better outcomes in terms of OS and progression-free survival (PFS) than assumed at time of study design, translating into prespecified NIMs or hazard ratios that reflected larger absolute differences in OS or PFS between arms. Lower-than-expected event rates also reduced statistical power for the trials. Other factors, including length of follow-up, cause of death, QOL, and primary end point, and their impact on trial interpretation are discussed. No trial to date has demonstrated survival superiority of IAD compared with CAD. Trials concluding IAD is noninferior to CAD were based on wide NIMs that included clinically important survival differences, not likely to be considered comparable by physicians or patients. Interim analyses relying on short follow-up and including a majority of non-prostate cancer deaths will favor a noninferiority conclusion and should be interpreted cautiously. Adequate follow-up is required to ensure capture of prostate cancer deaths in both superiority and noninferiority trials. © 2015 by American Society of Clinical Oncology.

  19. Unexpected Relationships and Inbreeding in HapMap Phase III Populations

    Science.gov (United States)

    Stevens, Eric L.; Baugher, Joseph D.; Shirley, Matthew D.; Frelin, Laurence P.; Pevsner, Jonathan

    2012-01-01

    Correct annotation of the genetic relationships between samples is essential for population genomic studies, which could be biased by errors or omissions. To this end, we used identity-by-state (IBS) and identity-by-descent (IBD) methods to assess genetic relatedness of individuals within HapMap phase III data. We analyzed data from 1,397 individuals across 11 ethnic populations. Our results support previous studies (Pemberton et al., 2010; Kyriazopoulou-Panagiotopoulou et al., 2011) assessing unknown relatedness present within this population. Additionally, we present evidence for 1,657 novel pairwise relationships across 9 populations. Surprisingly, significant Cotterman's coefficients of relatedness K1 (IBD1) values were detected between pairs of known parents. Furthermore, significant K2 (IBD2) values were detected in 32 previously annotated parent-child relationships. Consistent with a hypothesis of inbreeding, regions of homozygosity (ROH) were identified in the offspring of related parents, of which a subset overlapped those reported in previous studies (Gibson et al. 2010; Johnson et al. 2011). In total, we inferred 28 inbred individuals with ROH that overlapped areas of relatedness between the parents and/or IBD2 sharing at a different genomic locus between a child and a parent. Finally, 8 previously annotated parent-child relationships had unexpected K0 (IBD0) values (resulting from a chromosomal abnormality or genotype error), and 10 previously annotated second-degree relationships along with 38 other novel pairwise relationships had unexpected IBD2 (indicating two separate paths of recent ancestry). These newly described types of relatedness may impact the outcome of previous studies and should inform the design of future studies relying on the HapMap Phase III resource. PMID:23185369

  20. Mechanism of resistance of noncycling mammalian cells to 4'-(9-acridinylamino)methanesulfon-m-anisidide: comparison of uptake, metabolism, and DNA breakage in log- and plateau-phase Chinese hamster fibroblast cell cultures

    International Nuclear Information System (INIS)

    Robbie, M.A.; Baguley, B.C.; Denny, W.A.; Gavin, J.B.; Wilson, W.R.

    1988-01-01

    Resistance of noncycling cells to amsacrine (m-AMSA) has been widely reported and may limit the activity of this drug against solid tumors. The biochemical mechanism(s) for this resistance have been investigated using spontaneously transformed Chinese hamster fibroblasts (AA8 cells, a subline of Chinese hamster ovary-cells) in log- and plateau-phase spinner cultures. In early plateau phase most cells entered a growth-arrested state with a G1-G0 DNA content and showed a marked decrease in sensitivity to cytotoxicity induced by a 1-h exposure to m-AMSA or to its solid tumor-active analogue, CI-921. Studies with radiolabeled m-AMSA established that similar levels of drug were accumulated by log- and plateau-phase cells and that there was no significant drug metabolism in either of these cultures after 1 h. However, marked differences in sensitivity to m-AMSA-induced DNA breakage were observed using a fluorescence assay for DNA unwinding. Changes in sensitivity to DNA breakage occurred in parallel with changes in sensitivity to m-AMSA-induced cell killing. DNA breaks disappeared rapidly after drug removal (half-time approximately 4 min), suggesting that these lesions were probably mediated by DNA topoisomerase II. Resistance to m-AMSA may therefore be associated with changes in topoisomerase II activity in noncycling cells

  1. Encyclopedia of two-phase heat transfer and flow III macro and micro flow boiling and numerical modeling fundamentals

    CERN Document Server

    2018-01-01

    Set III of this encyclopedia is a new addition to the previous Sets I and II. It contains 26 invited chapters from international specialists on the topics of numerical modeling of two-phase flows and evaporation, fundamentals of evaporation and condensation in microchannels and macrochannels, development and testing of micro two-phase cooling systems for electronics, and various special topics (surface wetting effects, microfin tubes, two-phase flow vibration across tube bundles). The chapters are written both by renowned university researchers and by well-known engineers from leading corporate research laboratories. Numerous "must read" chapters cover the fundamentals of research and engineering practice on boiling, condensation and two-phase flows, two-phase heat transfer equipment, electronics cooling systems, case studies and so forth. Set III constitutes a "must have" reference together with Sets I and II for thermal engineering researchers and practitioners.

  2. Acute morbidity reduction using 3DCRT for prostate carcinoma; a randomised phase III study

    International Nuclear Information System (INIS)

    Koper, P.; Putten, W. van; Stroom, J.; Korevaar, G.; Heijmen, B.; Wijnmaalen, A.; Jansen, P.; Hanssens, P.; Griep, C.; Krol, A.; Samson, M.; Levendag, P.

    1997-01-01

    Purpose: A randomised phase III toxicity study (conventional vs conformal radiotherapy) was performed for prostatic carcinoma to study the effects on the (acute) morbidity of intestinal/rectosigmoid and bladder. The observed toxicity was compared with Dose Volume Histograms to reveal possible volume (reduction) effects. Methods: In the phase III study 266 T1-4 N0M0 prostate cancer patients were entered. Patients were randomised for conventional and conformal radiotherapy (total dose 66 Gy, minimum PTV dose 95% ICRU and a CTV-PTV margin of 10 mm in both study arms). The GTV was limited to the prostate only in T1 tumors. In all other patients the GTV was defined to be prostate and seminal vesicles for the complete treatment course. The CTV-PTV margin (10mm) was created by a automated program to ensure the minimum prescribed margin. The rectosigmoid was defined to be the rectum including the sigmoid within the Treatment Volume (ICRU). Acute toxicity was evaluated using the EORTC/RTOG morbidity score and weekly quality of life questionnaires. The radiation technique comparison was done by Dose volume Histogram analysis using the Area Under The Curve (AUC) for different dose levels. In this preliminary DVH analysis we present the data for the first 100 patients. Results: Patient and tumor characteristics were evenly distributed between both study groups. The maximum toxicity is reached at 75% of the tumordose (TD) (rectal grade I 59% grade II 26%, bladder grade I 48%, grade II 16% and grade III 1% [catheter for urinary retention]). Comparing both study arms there seems to be a reduction in intestinal morbidity (grade II and higher resp. 32% vs 19% p=0.02). Further analysis revealed a marked reduction in medication for anal symptoms; this accounts for a large part of the significant difference in intestinal toxicity (grade II conventional vs conformal rectosigmoid 18% vs 14% and anal 16% vs 8%). For bladder morbidity no difference for mobidity higher than grade I is

  3. Phase III Drilling Operations at the Long Valley Exploratory Well (LVF 51-20)

    Energy Technology Data Exchange (ETDEWEB)

    Finger, J.T.; Jacobson, R.D.

    1999-06-01

    During July-September, 1998, a jointly funded drilling operation deepened the Long Valley Exploratory Well from 7178 feet to 9832 feet. This was the third major drilling phase of a project that began in 1989, but had sporadic progress because of discontinuities in tiding. Support for Phase III came from the California Energy Commission (CEC), the International Continental Drilling Program (ICDP), the US Geological Survey (USGS), and DOE. Each of these agencies had a somewhat different agenda: the CEC wants to evaluate the energy potential (specifically energy extraction from magma) of Long Valley Caldera; the ICDP is studying the evolution and other characteristics of young, silicic calderas; the USGS will use this hole as an observatory in their Volcano Hazards program; and the DOE, through Sandia, has an opportunity to test new geothermal tools and techniques in a realistic field environment. This report gives a description of the equipment used in drilling and testing; a narrative of the drilling operations; compiled daily drilling reports; cost information on the project; and a brief summary of engineering results related to equipment performance and energy potential. Detailed description of the scientific results will appear in publications by the USGS and other researchers.

  4. Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design

    Directory of Open Access Journals (Sweden)

    Keppel Hesselink JM

    2017-03-01

    Full Text Available Jan M Keppel Hesselink,1 David J Kopsky,2 Stephen M Stahl3 1Institute Neuropathic Pain, Bosch en Duin, the Netherlands; 2Institute Neuropathic Pain, Amsterdam, the Netherlands; 3University of California San Diego, La Jolla, CA, USA Abstract: Topical analgesics can be defined as topical formulations containing analgesics or co-analgesics. Since 2000, interest in such formulations has been on the rise. There are, however, four critical issues in the research and development phases of topical analgesics: 1 The selection of the active pharmaceutical ingredient. Analgesics and co-analgesics differ greatly in their mechanism of action, and it is required to find the most optimal fit between such mechanisms of action and the pathogenesis of the targeted (neuropathic pain. 2 Issues concerning the optimized formulation. For relevant clinical efficacy, specific characteristics for the selected vehicle (eg, cream base or gel base are required, depending on the physicochemical characteristics of the active pharmaceutical ingredient(s to be delivered. 3 Well-designed phase II dose-finding studies are required, and, unfortunately, such trials are missing. In fact, we will demonstrate that underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. 4 Selection of clinical end points and innovatively designed phase III trials. End point selection can make or break a trial. For instance, to include numbness together with tingling as a composite end point for neuropathic pain seems stretching the therapeutic impact of an analgesic too far. Given the fast onset of action of topical analgesics (usually within 30 minutes, enrichment designs might enhance the chances for success, as the placebo response might decrease. Topical analgesics may become promising inroads for the treatment of neuropathic pain, once sufficient attention is given to these four key aspects. Keywords: topical, analgesics

  5. Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

    Science.gov (United States)

    Desjardins, Annick; Quinn, Jennifer A; Vredenburgh, James J; Sathornsumetee, Sith; Friedman, Allan H; Herndon, James E; McLendon, Roger E; Provenzale, James M; Rich, Jeremy N; Sampson, John H; Gururangan, Sridharan; Dowell, Jeannette M; Salvado, August; Friedman, Henry S; Reardon, David A

    2007-05-01

    Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

  6. Joint Operations 2030 - Phase III Report: The JO 2030 Capability Set (Operations interarmees 2030 - Rapport Phase III: L’ensemble capacitaire JO 2030)

    Science.gov (United States)

    2011-04-01

    Registry for EU and ul. Ostrobramska 109 NATO FRANCE 04-041 Warszawa Vojkova 55 O.N.E.R.A. (ISP) 1000 Ljubljana 29, Avenue de la Division...Ostrobramska 109 Dstl Knowledge and Information Streitkräfteamt / Abteilung III 04-041 Warszawa Services Fachinformationszentrum der Bundeswehr (FIZBw

  7. Microbial Reducibility of Fe(III Phases Associated with the Genesis of Iron Ore Caves in the Iron Quadrangle, Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Ceth W. Parker

    2013-11-01

    Full Text Available The iron mining regions of Brazil contain thousands of “iron ore caves” (IOCs that form within Fe(III-rich deposits. The mechanisms by which these IOCs form remain unclear, but the reductive dissolution of Fe(III (hydroxides by Fe(III reducing bacteria (FeRB could provide a microbiological mechanism for their formation. We evaluated the susceptibility of Fe(III deposits associated with these caves to reduction by the FeRB Shewanella oneidensis MR-1 to test this hypothesis. Canga, an Fe(III-rich duricrust, contained poorly crystalline Fe(III phases that were more susceptible to reduction than the Fe(III (predominantly hematite associated with banded iron formation (BIF, iron ore, and mine spoil. In all cases, the addition of a humic acid analogue enhanced Fe(III reduction, presumably by shuttling electrons from S. oneidensis to Fe(III phases. The particle size and quartz-Si content of the solids appeared to exert control on the rate and extent of Fe(III reduction by S. oneidensis, with more bioreduction of Fe(III associated with solid phases containing more quartz. Our results provide evidence that IOCs may be formed by the activities of Fe(III reducing bacteria (FeRB, and the rate of this formation is dependent on the physicochemical and mineralogical characteristics of the Fe(III phases of the surrounding rock.

  8. A survey of Type III restriction-modification systems reveals numerous, novel epigenetic regulators controlling phase-variable regulons; phasevarions

    Science.gov (United States)

    Atack, John M; Yang, Yuedong; Jennings, Michael P

    2018-01-01

    Abstract Many bacteria utilize simple DNA sequence repeats as a mechanism to randomly switch genes on and off. This process is called phase variation. Several phase-variable N6-adenine DNA-methyltransferases from Type III restriction-modification systems have been reported in bacterial pathogens. Random switching of DNA methyltransferases changes the global DNA methylation pattern, leading to changes in gene expression. These epigenetic regulatory systems are called phasevarions — phase-variable regulons. The extent of these phase-variable genes in the bacterial kingdom is unknown. Here, we interrogated a database of restriction-modification systems, REBASE, by searching for all simple DNA sequence repeats in mod genes that encode Type III N6-adenine DNA-methyltransferases. We report that 17.4% of Type III mod genes (662/3805) contain simple sequence repeats. Of these, only one-fifth have been previously identified. The newly discovered examples are widely distributed and include many examples in opportunistic pathogens as well as in environmental species. In many cases, multiple phasevarions exist in one genome, with examples of up to 4 independent phasevarions in some species. We found several new types of phase-variable mod genes, including the first example of a phase-variable methyltransferase in pathogenic Escherichia coli. Phasevarions are a common epigenetic regulation contingency strategy used by both pathogenic and non-pathogenic bacteria. PMID:29554328

  9. 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...

  10. The Effects of PECS Teaching to Phase III on the Communicative Interactions between Children with Autism and Their Teachers

    Science.gov (United States)

    Carr, Deborah; Felce, Janet

    2007-01-01

    The study investigated the impact of mastery of the Picture Exchange Communication System (PECS) to Phase III, on the communications of children with autism. Children aged between 3 and 7 years, formed a PECS intervention group and a non-intervention control group. The intervention group received 15 h of PECS teaching over 5 weeks. Three 2-h…

  11. SPSP Phase III Recruiting, Selecting, and Developing Secure Power Systems Professionals: Behavioral Interview Guidelines by Job Roles

    Energy Technology Data Exchange (ETDEWEB)

    O' Neil, Lori Ross [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Conway, T. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tobey, D. H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Greitzer, Frank L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dalton, Angela C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Pusey, Portia K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-03-01

    The Secure Power Systems Professional Phase III final report was released last year which an appendix of Behavioral Interview Guidelines by Job Roles. This new report is that appendix broken out as a standalone document to assist utilities in recruiting and developing Secure Power Systems Professionals at their site.

  12. Assessing braze quality in the actively cooled Tore Supra phase III outboard pump limiter

    International Nuclear Information System (INIS)

    Hygren, R.; Lutz, T.; Miller, J.

    1994-01-01

    This paper discusses the assessment of quality of brazing of pyrolytic graphite (PG) armor brazed to copper tubes in Tore Supra's Phase III Outboard Pump Limiter (OPL). The limiter head is a bank of 14 water-cooled copper tubes with several hundred brazed PG tiles. Braze quality was first assessed through pre-service qualification testing of individual copper/tiles assemblies. The quality of brazes was evaluated using (non-destructive) transient heating (open-quotes hot waterclose quotes) tests performed in the high temperature, high pressure flow loop at Sandia's Plasma Materials Test Facility. The surface temperatures of tiles were monitored with an infra-red (IR) camera as water at 120 degrees C water at about 2.07 MPa (300 psi) passed through a tube assembly initially at 30 degrees C. For tiles with braze voids or cracks, the surface temperatures lagged behind those of adjacent well bonded tiles. Temperature lags were correlated with flaw sizes observed during repairs using a detailed 2-D heat transfer analyses. open-quotes Badclose quotes tiles, i.e., temperature lags of 10-20 degrees C depending upon tile's size, were easy to detect and, when removed, revealed braze voids of roughly 50% of the joint area. 11 of the 14 tubes were rebrazed after bad tiles were detected and removed. Three tubes were re-brazed twice

  13. Tier I ecological evaluation for phase III channel improvements to the John. F. Baldwin ship channel

    Energy Technology Data Exchange (ETDEWEB)

    Bienert, R.W.; Shreffler, D.K.; Word, J.Q.; Kohn, N.P. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

    1994-05-01

    To assist the US Army Corps of Engineers (USACE) in determing whether the material from proposed dredging of the John F. Baldwin Ship Channel (JFBSC) is suitable for unrestricted, unconfined open-ocean disposal, Battelle/Marine Sciences Laboratory (MSL) prepared this report. Based on these findings, sediments that would be removed during Phase III improvements to the JFBSC fail to meet the three suitability criteria for open-ocean disposal. Firstly, fine-grained sediments comprise a significant fraction of the bottom material in some areas of the channel, and this material is not exposed to high current or wave energy. Dredged material from the JFBSC is not being proposed for beach nourishment; therefore the second criterion is not met. JFBSC sediments do not meet the third criterion because, although they may be substantially similar to substrates at several of the proposed disposal sites, they are from an area that historically has experienced loading of contaminants, which toxicology studies have shown have the potential to result in acute toxicity or significant bioaccumulation.

  14. SPIRIT: A seamless phase I/II randomized design for immunotherapy trials.

    Science.gov (United States)

    Guo, Beibei; Li, Daniel; Yuan, Ying

    2018-06-07

    Immunotherapy-treatments that enlist the immune system to battle tumors-has received widespread attention in cancer research. Due to its unique features and mechanisms for treating cancer, immunotherapy requires novel clinical trial designs. We propose a Bayesian seamless phase I/II randomized design for immunotherapy trials (SPIRIT) to find the optimal biological dose (OBD) defined in terms of the restricted mean survival time. We jointly model progression-free survival and the immune response. Progression-free survival is used as the primary endpoint to determine the OBD, and the immune response is used as an ancillary endpoint to quickly screen out futile doses. Toxicity is monitored throughout the trial. The design consists of two seamlessly connected stages. The first stage identifies a set of safe doses. The second stage adaptively randomizes patients to the safe doses identified and uses their progression-free survival and immune response to find the OBD. The simulation study shows that the SPIRIT has desirable operating characteristics and outperforms the conventional design. Copyright © 2018 John Wiley & Sons, Ltd.

  15. Solid phase extraction of Am (III) by resins impregnated with multiply diglycolamide-functionalized ligands

    International Nuclear Information System (INIS)

    Gujar, R.B.; Ansari, S.A.; Mohapatra, P.K.; Verboom, W.

    2016-01-01

    Solvent extraction studies with multiply diglycolamide-functionalized extractants such as tripodal diglycolamide (T-DGA) or diglycolamide-functionalized calix(4)arene (C4DGA) ligands have shown excellent results as compared to those of normal DGA ligands such as TODGA. A very high selectivity for Am(III) has been reported with these ligands with respect to U(VI) and Pu(IV). High selectivities and large extraction efficiencies of these ligands towards trivalent f elements were ascribed to a co-operative complexation mechanism. Furthermore, the extraction efficiency of these ligands increased several folds in ionic liquid medium as compared to paraffinic solvents. It was of interest, therefore, to prepare extraction chromatographic resins by impregnation of solvent systems containing these ligands in an ionic liquid. In the present work, solid phase extraction studies were carried out using these two multiply diglycolamide-functionalized extractants, viz. T-DGA (resin I) and C4DGA (resin-II) containing the ionic liquid C 4 mim. NTf 2 impregnated on Chromosorb-W

  16. Optimized FFTF Acceptance Test Program covering Phases III, IV, and V

    International Nuclear Information System (INIS)

    Wykoff, W.R.; Jones, D.H.

    1977-03-01

    A detailed review of Phases III, IV, and V of the FFTF Acceptance Test Program has been completed. The purpose of this review was to formulate that test sequence which not only meets requirements for safe, reliable and useful operation of the plant, but also results in the earliest prudent demonstration of full-power performance. A test sequence based on the underlying assumption that sodium flows into the secondary sodium storage tank (T-44) no later than August 31, 1978, is described in detail. A time-scale which allows extra time to put systems and equipment into operation the first time, debugging, and learning how to operate most effectively has been superimposed on the test sequence. Time is not included for major equipment malfunctions. This test plan provides the basis for coordinating the many and varied activities and interfaces necessary for successful and timely execution of the FFTF Acceptance Test Program. In this report, the need dates have been identified for presently scheduled test articles and standard core components

  17. Differences in Funding Sources of Phase III Oncology Clinical Trials by Treatment Modality and Cancer Type.

    Science.gov (United States)

    Jairam, Vikram; Yu, James B; Aneja, Sanjay; Wilson, Lynn D; Lloyd, Shane

    2017-06-01

    Given the limited resources available to conduct clinical trials, it is important to understand how trial sponsorship differs among different therapeutic modalities and cancer types and to consider the ramifications of these differences. We searched clinicaltrials.gov for a cross-sectional register of active, phase III, randomized controlled trials (RCTs) studying treatment-related endpoints such as survival and recurrence for the 24 most prevalent malignancies. We classified the RCTs into 7 categories of therapeutic modality: (1) chemotherapy/other cancer-directed drugs, (2) targeted therapy, (3) surgery, (4) radiation therapy (RT), (5) RT with other modalities, (6) multimodality therapy without RT, and (7) other. RCTs were categorized as being funded by one or more of the following groups: (1) government, (2) hospital/university, (3) industry, and (4) other. χ analysis was performed to detect differences in funding source distribution between modalities and cancer types. The percentage of multimodality trials (5%) and radiation RCTs (4%) funded by industry was less than that for chemotherapy (32%, Pfunding than any of the other modalities (Pfunded by industry if they also studied targeted therapy (Pfunded by industry than trials studying multimodality therapy or radiation. The impact of industry funding versus institutional or governmental sources of funding for cancer research is unclear and requires further study.

  18. Assessing braze quality in the actively cooled Tore Supra Phase III outboard pump limiter

    International Nuclear Information System (INIS)

    Nygren, R.E.; Lutz, T.L.; Miller, J.D.; McGrath, R.; Dale, G.

    1994-01-01

    The quality of brazing of pyrolytic graphite armor brazed to copper tubes in Tore Supra's Phase III Outboard Pump Limiter was assessed through pre-service qualification testing of individual copper/tile assemblies. The evaluation used non-destructive, hot water transient heating tests performed in the high-temperature, high-pressure flow loop at Sandia's Plasma Materials Test Facility. Surface temperatures of tiles were monitored with an infrared camera as water at 120 degrees C at about 2.07 MPa (300 psi) passed through a tube assembly initially at 30 degrees C. For tiles with braze voids or cracks, the surface temperatures tagged behind those of adjacent well-bonded tiles. Temperature tags were correlated with flaw sizes observed during repairs based upon a detailed 2-D heat transfer analyses. open-quotes Badclose quotes tiles, i.e., temperature tags of 10-20 degrees C depending upon tile's size, were easy to detect and, when removed, revealed braze voids of roughly 50% of the joint area. Eleven of the 14 tubes were rebrazed after bad tiles were detected and removed. Three tubes were rebrazed twice

  19. Growth, structure and phase transitions of epitaxial nanowires of III-V semiconductors

    International Nuclear Information System (INIS)

    Glas, F; Patriarche, G; Harmand, J C

    2010-01-01

    We review and illustrate the impact of TEM on the study of nanowires of non-nitride III-V semiconductors, with particular emphasis on the understanding of the thermodynamics and kinetics of their formation assisted by nano-sized catalyst particles. Besides providing basic information about the morphology of the nanowires and their growth rate as a function of diameter, TEM offers insights into the peculiar crystalline structure that they adopt. We discuss the formation of the unusual wurtzite hexagonal crystalline phase and that of planar stacking defects in these nanowires and show that they are kinetically controlled. We also demonstrate the transformation of wurtzite into cubic sphalerite upon epitaxial burying of the nanowires. Nanowires are particularly interesting in that they allow the fabrication of precisely positioned quantum dots with well-defined geometries. In this respect, we discuss the formation of strained quantum-size inclusions in nanowires, their critical dimensions and the kinetic and thermodynamic factors governing the changes of the crystalline structure that sometimes occur around a hetero-interface.

  20. Analysis of gas-liquid metal two-phase flows using a reactor safety analysis code SIMMER-III

    International Nuclear Information System (INIS)

    Suzuki, Tohru; Tobita, Yoshiharu; Kondo, Satoru; Saito, Yasushi; Mishima, Kaichiro

    2003-01-01

    SIMMER-III, a safety analysis code for liquid-metal fast reactors (LMFRs), includes a momentum exchange model based on conventional correlations for ordinary gas-liquid flows, such as an air-water system. From the viewpoint of safety evaluation of core disruptive accidents (CDAs) in LMFRs, we need to confirm that the code can predict the two-phase flow behaviors with high liquid-to-gas density ratios formed during a CDA. In the present study, the momentum exchange model of SIMMER-III was assessed and improved using experimental data of two-phase flows containing liquid metal, on which fundamental information, such as bubble shapes, void fractions and velocity fields, has been lacking. It was found that the original SIMMER-III can suitably represent high liquid-to-gas density ratio flows including ellipsoidal bubbles as seen in lower gas fluxes. In addition, the employment of Kataoka-Ishii's correlation has improved the accuracy of SIMMER-III for gas-liquid metal flows with cap-shape bubbles as identified in higher gas fluxes. Moreover, a new procedure, in which an appropriate drag coefficient can be automatically selected according to bubble shape, was developed. Through this work, the reliability and the precision of SIMMER-III have been much raised with regard to bubbly flows for various liquid-to-gas density ratios

  1. Long-Term Management Strategy for Dredged Material Disposal for Naval Facilities at Pearl Harbor, Hawaii Phase III - Analysis of Alternatives and Development of an LTMS

    National Research Council Canada - National Science Library

    Palermo, Michael

    2000-01-01

    This report documents Phase III of a three-phase study to develop a Long-Term Management Study for disposal of dredged material unsuitable for ocean disposal from Pearl Harbor Naval Complex for the next 30 years...

  2. Optimal scheme of postoperative chemoradiotherapy in rectal cancer: phase III prospective randomized trial

    International Nuclear Information System (INIS)

    Kim, Young Seok; Kim, Jong Hoon; Choi, Eun Kyung

    2002-01-01

    To determine the optimal scheme of postoperative chemoradiotherapy in rectal cancer by comparing survival, patterns of failure, toxicities in early and late radiotherapy groups using a phase III randomized prospective clinical trial. From January 1996 to March 1999, 307 patients with curatively resected AJCC stage II and III rectal cancer were assigned randomly to an 'early (151 patients, arm I)' or a 'late (156 patients, arm II)' and were administered combined chemotherapy (5-FU 375 mg/m 2 /day, leucovorin 20 mg/m 2 , IV bolus daily, for 3 days with RT, 5 days without RT, 8 cycles with 4 weeks interval) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Patients of arm I received radiation therapy from day 1 of the first cycle of chemotherapy and those of arm II from day 57 with a third cycle of chemotherapy. The median follow-up period of living patients was 40 months. Of the 307 patients enrolled, fifty patients did not receive scheduled radiation therapy or chemotherapy. The overall survival rate and disease free survival rate at 5 years were 78.3% and 68.7% in arm I, and 78.4% and 67.5% in arm II. The local recurrence rate was 6.6% and 6.4% (ρ = 0.46) in arms I and II, respectively, no significant difference was observed between the distant metastasis rates of the two arms (23.8% and 29.5%, ρ = 0.16). During radiation therapy, grade 3 diarrhea or more, by the NCI common toxicity criteria, was observed in 63.0% and 58.2% of the respective arms (ρ = N.S.), but most were controlled with supportive care. Hematologic toxicity (leukopenia) greater than RTOG grade 2 was found in only 1.3% and 2.6% of patients in each respective arm. There was no significant difference in survival, patterns of failure or toxicities between the early and late radiation therapy arms. Postoperative adjuvant chemoradiation was found to be a relatively safe treatment but higher compliance is needed

  3. Modeling the Physical Multi-Phase Interactions of HNO3 Between Snow and Air on the Antarctic Plateau (Dome C) and coast (Halley)

    Science.gov (United States)

    Chan, Hoi Ga; Frey, Markus M.; King, Martin D.

    2017-04-01

    Nitrogen oxides (NOx = NO + NO2) emissions from nitrate (NO3-) photolysis in snow affect the oxidising capacity of the lower troposphere especially in remote regions of the high latitudes with low pollution levels. The porous structure of snowpack allows the exchange of gases with the atmosphere driven by physicochemical processes, and hence, snow can act as both source and sink of atmospheric chemical trace gases. Current models are limited by poor process understanding and often require tuning parameters. Here, two multi-phase physical models were developed from first principles constrained by observed atmospheric nitrate, HNO3, to describe the air-snow interaction of nitrate. Similar to most of the previous approaches, the first model assumes that below a threshold temperature, To, the air-snow grain interface is pure ice and above To, a disordered interface (DI) emerges assumed to be covering the entire grain surface. The second model assumes that Air-Ice interactions dominate over the entire temperature range below melting and that only above the eutectic temperature, liquid is present in the form of micropockets in grooves. The models are validated with available year-round observations of nitrate in snow and air at a cold site on the Antarctica Plateau (Dome C, 75°06'S, 123°33'E, 3233 m a.s.l.) and at a relatively warm site on the Antarctica coast (Halley, 75°35'S, 26°39'E, 35 m a.s.l). The first model agrees reasonably well with observations at Dome C (Cv(RMSE) = 1.34), but performs poorly at Halley (Cv(RMSE) = 89.28) while the second model reproduces with good agreement observations at both sites without any tuning (Cv(RMSE) = 0.84 at both sites). It is therefore suggested that air-snow interactions of nitrate in the winter are determined by non-equilibrium surface adsorption and co-condensation on ice coupled with solid-state diffusion inside the grain. In summer, however, the air-snow exchange of nitrate is mainly driven by solvation into liquid

  4. Utilization of modified corn silk as a biosorbent for solid-phase extraction of Cr(III) and chromium speciation.

    Science.gov (United States)

    Yu, Hongmei; Pang, Jing; Wu, Mei; Wu, Qiaoli; Huo, Cuixiu

    2014-01-01

    The ues of corn silk modified with diluted nitric acid (HNO3-MCS) as a novel biosorbent has been established for solid-phase extraction of Cr(III) and chromium speciation in water samples. The functional groups of the HNO3-MCS surface are favorable for the adsorption of Cr(III). Effective extraction conditions were optimized in both batch and column methods. At pH 3.0 - 6.0, a discrimination of Cr(III) and Cr(VI) is achieved on the HNO3-MCS surface. Cr(III) ions are retained onto the HNO3-MCS surface, however, the adsorption of Cr(VI) is negligible under the same conditions. The adsorption isotherm of HNO3-MCS for Cr(III) has been demonstrated in accordance with a linear form of the Langmuir equation, and the maximum adsorption capacity is 35.21 mg g(-1). The well fitted linear regression of the pseudo-second order model showed the indication of a chemisorption mechanism for the entire concentration range. Thermodynamic studies have shown that the adsorption process is spontaneous and endothermic. The adsorbed Cr(III) was quantitatively eluted by a nitric acid solution with detection by flame atomic absorption spectrometry (FAAS). With a sample volume of 30 mL, a detection limit (3σ) of 0.85 μg L(-1) and a precision of 2.0% RSD at the 40 μg L(-1) level were achieved. The concentration of Cr(III) could be accurately quantified within a linear range of 3 - 200 μg L(-1). After Cr(VI) has been reduced to Cr(III) with hydroxylamine hydrochloride, the total amount of chromium was obtained, and the content of Cr(VI) was given by subtraction. The procedure was validated by analyzing chromium in a certified reference material (GBW (E) 080039). It was also successfully applied for the speciation of chromium in wastewater samples.

  5. Radiation therapy for ocular choroidal neovascularization (phase I/II study): preliminary report

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Ogura, Yuichiro; Ngata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

    1997-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angioid streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well-demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the sub retinal neovascular membranes in CNV. We conducted a Phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Methods and Materials: Between April, 1994 and July, 1995, 36 patients with choroidal neovascularization (34 with ARMD and 2 with angioid streaks) were treated with radiation therapy. Treatment planning was performed using a CT simulator that enables real-time treatment planning from multiple CT slices. The clinical target volume that included the macula and optic disc received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions/2 weeks (last 18 eyes). All eyes were irradiated with a single lateral 6 MV photon beam, angled 10 degrees posteriorly to exclude the ipsilateral lens and the contralateral eye from the radiation field. The ipsilateral lens was irradiated with less than 10% of the total reference dose. The field size averaged 3.0 x 2.5 cm. Records of the 17 eyes with CNV referred to our hospital in 1993, which satisfied the eligibility criteria for this study, were retrospectively analyzed for comparison. Results: There was no significant acute morbidity. All patients were followed regularly by both ophthalmologists and radiation oncologists. Cataract formation after 1 year of the treatment was observed in one patient who had received a dose of 20 Gy. One patient who had received 20 Gy complained of transient dry-eye sensation

  6. Study of complex formation of cobalt (II) and cobalt (III) in acrylamide aqueous solutions and in the phase of acrylamide hydrogel

    International Nuclear Information System (INIS)

    Ismailova, M.M.; Egorova, L.A.; Khamidov, B.O.

    1993-01-01

    Present article is devoted to study of complex formation of cobalt (II) and cobalt (III) in acrylamide aqueous solutions and in the phase of acrylamide hydrogel. The condition of cobalt in various rate of oxidation in acrylamide aqueous solutions was studied. The concentration conditions of stability of system Co(II)-Co(III) were defined. The composition of coordination compounds of cobalt (II) and cobalt (III) in acrylamide aqueous solutions and in the phase of acrylamide hydrogel was determined.

  7. How Accurately Do Consecutive Cohort Audits Predict Phase III Multisite Clinical Trial Recruitment in Palliative Care?

    Science.gov (United States)

    McCaffrey, Nikki; Fazekas, Belinda; Cutri, Natalie; Currow, David C

    2016-04-01

    Audits have been proposed for estimating possible recruitment rates to randomized controlled trials (RCTs), but few studies have compared audit data with subsequent recruitment rates. To compare the accuracy of estimates of potential recruitment from a retrospective consecutive cohort audit of actual participating sites and recruitment to four Phase III multisite clinical RCTs. The proportion of potentially eligible study participants estimated from an inpatient chart review of people with life-limiting illnesses referred to six Australian specialist palliative care services was compared with recruitment data extracted from study prescreening information from three sites that participated fully in four Palliative Care Clinical Studies Collaborative RCTs. The predominant reasons for ineligibility in the audit and RCTs were analyzed. The audit overestimated the proportion of people referred to the palliative care services who could participate in the RCTs (pain 17.7% vs. 1.2%, delirium 5.8% vs. 0.6%, anorexia 5.1% vs. 0.8%, and bowel obstruction 2.8% vs. 0.5%). Approximately 2% of the referral base was potentially eligible for these effectiveness studies. Ineligibility for general criteria (language, cognition, and geographic proximity) varied between studies, whereas the reasons for exclusion were similar between the audit and pain and anorexia studies but not for delirium or bowel obstruction. The retrospective consecutive case note audit in participating sites did not predict realistic recruitment rates, mostly underestimating the impact of study-specific inclusion criteria. These findings have implications for the applicability of the results of RCTs. Prospective pilot studies are more likely to predict actual recruitment. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  8. Diet and Respiratory Health in Children from 11 Latin American Countries: Evidence from ISAAC Phase III.

    Science.gov (United States)

    Cepeda, Alfonso Mario; Thawer, Sumaiyya; Boyle, Robert J; Villalba, Sara; Jaller, Rodolfo; Tapias, Elmy; Segura, Ana María; Villegas, Rodrigo; Garcia-Larsen, Vanessa

    2017-12-01

    The burden of childhood asthma and its risk factors is an important but neglected public health challenge in Latin America. We investigated the association between allergic symptoms and dietary intake in children from this region. As part of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase III, questionnaire collected dietary intake was investigated in relation to risk of parental/child reported current wheeze (primary outcome) and rhino-conjunctivitis and eczema. Per-country adjusted logistic regressions were performed, and combined effect sizes were calculated with meta-analyses. 143,967 children from 11 countries had complete data. In children aged 6-7 years, current wheeze was negatively associated with higher fruit intake (adjusted odds ratio [aOR] 0.65; 95% CI 0.74, 0.97). Current rhino-conjunctivitis and eczema were statistically negatively associated with fruit intake (aOR 0.72; 95% CI 0.64, 0.82; and OR 0.64, 95% CI 0.56, 0.74, respectively). Vegetable intake was negatively associated with risk of symptoms in younger children, but these associations were attenuated in the 13-14 years old group. Fastfood/burger intake was positively associated with all three outcomes in the older children. A higher intake of fruits and vegetables was associated with a lower prevalence of allergic symptoms in Latin American children. Conversely, intake of fastfood was positively associated with a higher prevalence of wheeze in adolescents. Improved dietary habits in children might help reduce the epidemic of allergic symptoms in Latin America. Food interventions in asthmatic children are needed to evaluate the possible public health impact of a better diet on respiratory health.

  9. Combining dosimetry and toxicity: analysis of two UK phase III clinical trials

    International Nuclear Information System (INIS)

    Gulliford, Sarah L

    2014-01-01

    There are many advantages to performing a clinical trial when implementing a novel radiotherapy technique. The clinical trials framework enables the safety and efficacy of the 'experimental arm' to be tested and ensures practical support, rigorous quality control and data monitoring for participating centres. In addition to the clinical and follow-up data collected from patients within the trial, it is also possible to collect 3-D dosimetric information from the corresponding radiotherapy treatment plans. Analysing the combination of dosimetric, clinical and follow-up data enhances the understanding of the relationship between the dose delivered to both the target and normal tissue structures and reported outcomes and toxicity. Aspects of the collection, collation and analysis of data from two UK multicentre Phase III radiotherapy trials are presented here. MRC-RT01 dose-escalation prostate radiotherapy trial ISRCTN47772397 was one of the first UK multi-centre radiotherapy trials to collect 3-D dosimetric data. A number of different analysis methodologies were implemented to investigate the relationship between the dose distribution to the rectum and specific rectal toxicities. More recently data was collected from the PARSPORT trial (Parotid Sparing IMRT vs conventional head and neck radiotherapy) ISRCTN48243537. In addition to the planned analysis, dosimetric analysis was employed to investigate an unexpected finding that acute fatigue was more prevalent in the IMRT arm of the trial. It can be challenging to collect 3-D dosimetric information from multicentre radiotherapy trials. However, analysing the relationship between dosimetric and toxicity data provides invaluable information which can influence the next generation of radiotherapy techniques.

  10. 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

  11. Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects

    International Nuclear Information System (INIS)

    Coleman, C. Norman; Kelly, Laura; Riese Daly, Nancy; Beard, Clair; Kaplan, Irving; Lamb, Carolyn; Propert, Kathleen; Manola, Judith

    2002-01-01

    Purpose: On the basis of our anecdotal clinical observations that nonsteroidal anti-inflammatory agents relieved dysuria during radiotherapy for patients with prostate cancer, we conducted a Phase III randomized trial of ibuprofen vs. placebo for patients who had an increase in acute urinary symptoms. Our in vitro and in vivo laboratory data with a higher concentration of ibuprofen than achievable in this study demonstrated radiosensitization. This study examined whether the inflammatory response within the prostate during radiotherapy would respond to the standard dose of ibuprofen as assessed by a symptom score. Methods and Materials: Patients were registered to the study and were followed weekly with a formal symptom assessment. A double-blind randomization to ibuprofen, 400 mg q.i.d., vs. placebo for 7 days was done at a time when the severity score increased. The symptom response was evaluated at the end of the week. Results: Between 1995 and 1998, 100 patients were entered, 28 did not have a sufficient change in symptom score to be randomized, and 19 were either unable to take ibuprofen or withdrew before randomization. Of the 53 patients randomized, 27 received placebo and 26 ibuprofen. No statistically significant differences were found between the placebo and ibuprofen groups between baseline and randomization or between randomization and the 1-week posttreatment assessment. Neither group had a change in symptom severity between randomization and the 1-week posttreatment evaluation. Conclusion: The standard anti-inflammatory dose of ibuprofen did not relieve the acute urinary or rectal symptoms during radiotherapy for prostate cancer. The nonsteroidal anti-inflammatory drugs are potential radiation sensitizers with the mechanism of action as yet unknown. Clinical trials of the cyclooxygenase inhibitors as radiation sensitizers should explore a range of doses and evaluate potential mechanisms of action, including cyclooxygenase inhibition and other non

  12. Steady-state heat and particle removal with the actively cooled Phase III outboard pump limiter in Tore Supra

    International Nuclear Information System (INIS)

    Nygren, R.; Koski, J.; Lutz, T.; McGrath; Miller, J.; Watkins, J.; Guilhem, D.; Chappuis, P.; Cordier, J.; Loarer, T.

    1995-01-01

    Tore Supra's Phase III outboard pump limiter (OPL) is a modular actively-cooled mid-plane limiter, designed for heat and particle removal during long pulse operation. During its initial operation in 1993, the OPL successfully removed about 1 MW of power during ohmicly heated shots of up to 10 s duration and reached (steady state) thermal equilibrium. The particle pumping of the Phase III OPL was found to be about 50% greater than the Phase II OPL which had a radial distance between the last closed flux surface and the entrance of the pumping throat of 3.5 cm compared with only 2.5 cm for the Phase III OPL. This paper gives examples of power distribution over the limiter from IR measurements of surface temperature and from extensively calorimetry (34 thermocouples and 10 flow meters) and compares the distributions with values predicted by a 3D model (HF3D) with a detailed magnetic configuration (e.g., includes field ripple). ((orig.))

  13. Motivation and participation in a phase III cardiac rehabilitation programme: an application of the health action process approach.

    Science.gov (United States)

    Dohnke, Birte; Nowossadeck, Enno; Müller-Fahrnow, Werner

    2010-10-01

    This longitudinal study extends the previous research on low participation rates and high dropout rates in phase III cardiac rehabilitation (CR) exercise programmes. It examines the correlates of motivation and participation 6 months after inpatient phase II CR (T1) and the predictors of dropout 6 months later (T2) using the health action process approach (HAPA). Risk perception, outcome expectancies, self-efficacy, intention (at T1), and participation (at T1 and T2) in relation to phase III CR programmes was assessed in 456 patients. Based on intention and participation at T1, patients were classified as nonintenders (56%), intenders (13%), or actors (31%). Group differences were confirmed in outcome expectancies and self-efficacy. By T2, 21% of T1 actors had dropped out. Dropouts and maintainers differed in intention and self-efficacy (at T1). Results are in line with the HAPA and suggest a perspective for tailoring motivational counselling to improve participation in phase III CR programmes.

  14. Remedial Design/Remedial Action Work Plan for Operable Units 6-05 and 10-04, Phase III

    Energy Technology Data Exchange (ETDEWEB)

    R. P. Wells

    2006-09-19

    The remedial design/remedial action for Operable Unit 6-05 (Waste Area Group 6) and Operable Unit 10-04 (Waste Area Group 10) - collectively called Operable Unit 10-04 has been divided into four phases. Phase I consists of developing and implementing institutional controls at Operable Unit 10-04 sites and developing and implementing Idaho National Laboratory-wide plans for both institutional controls and ecological monitoring. Phase II will remediate sites contaminated with trinitrotoluene and Royal Demolition Explosive. Phase III will remediate lead contamination at a gun range, and Phase IV will remediate hazards from unexploded ordnance. This Phase III remedial Design/Remedial Action Work Plan addresses the remediation of lead-contaminated soils found at the Security Training Facility (STF)-02 Gun Range located at the Idaho National Laboratory. Remediation of the STF-02 Gun Range will include excavating contaminated soils; physically separating copper and lead for recycling; returning separated soils below the remediation goal to the site; stabilizing contaminated soils, as required, and disposing of the separated soils that exceed the remediation goal; encapsulating and disposing of creosote-contaminated railroad ties and power poles; removing and disposing of the wooden building and asphalt pads found at the STF-02 Gun Range; sampling and analyzing soil to determine the excavation requirements; and when the remediation goals have been met, backfilling and contouring excavated areas and revegetating the affected area.

  15. TAILORING INORGANIC SORBENTS FOR SRS STRONTIUM AND ACTINIDE SEPARATIONS: MODIFIED MONOSODIUM TITANATE PHASE III FINAL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Taylor-Pashow, K.; Hobbs, D.

    2010-09-01

    This document provides a final report of Phase III testing activities for the development of modified monosodium titanate (mMST), which exhibits improved strontium and actinide removal characteristics compared to the baseline MST material. The activities included characterization of the crystalline phases present at varying temperatures, solids settling characteristics, quantification of the peroxide content; evaluation of the post-synthesis gas release under different conditions; the extent of desorption of {sup 85}Sr, Np, and Pu under washing conditions; and the effects of age and radiation on the performance of the mMST. Key findings and conclusions include the following. The peroxide content of several mMST samples was determined using iodometric titration. The peroxide content was found to decrease with age or upon extended exposure to elevated temperature. A loss of peroxide was also measured after exposure of the material to an alkaline salt solution similar in composition to the simulated waste solution. To determine if the loss of peroxide with age affects the performance of the material, Sr and actinide removal tests were conducted with samples of varying age. The oldest sample (4 years and 8 months) did show lower Sr and Pu removal performance. When compared to the youngest sample tested (1 month), the oldest sample retained only 15% of the DF for Pu. Previous testing with this sample indicated no decrease in Pu removal performance up to an age of 30 months. No loss in Np removal performance was observed for any of the aged samples, and no uptake of uranium occurred at the typical sorbent loading of 0.2 g/L. Additional testing with a uranium only simulant and higher mMST loading (3.0 g/L) indicated a 10% increase of uranium uptake for a sample aged 3 years and 8 months when compared to the results of the same sample measured at an age of 1 year and 5 months. Performance testing with both baseline-MST and mMST that had been irradiated in a gamma source to

  16. Waste retrieval sluicing system vapor sampling and analysis plan for evaluation of organic emissions, process test phase III

    International Nuclear Information System (INIS)

    SASAKI, L.M.

    1999-01-01

    This sampling and analysis plan identifies characterization objectives pertaining to sample collection, laboratory analytical evaluation, and reporting requirements for vapor samples obtained to address vapor issues related to the sluicing of tank 241-C-106. Sampling will be performed in accordance with Waste Retrieval Sluicing System Emissions Collection Phase III (Jones 1999) and Process Test Plan Phase III, Waste Retrieval Sluicing System Emissions Collection (Powers 1999). Analytical requirements include those specified in Request for Ecology Concurrence on Draft Strategy/Path Forward to Address Concerns Regarding Organic Emissions from C-106 Sluicing Activities (Peterson 1998). The Waste Retrieval Sluicing System was installed to retrieve and transfer high-heat sludge from tank 241-C-106 to tank 241-AY-102, which is designed for high-heat waste storage. During initial sluicing of tank 241-C-106 in November 1998, operations were halted due to detection of unexpected high volatile organic compounds in emissions that exceeded regulatory permit limits. Several workers also reported smelling sharp odors and throat irritation. Vapor grab samples from the 296-C-006 ventilation system were taken as soon as possible after detection; the analyses indicated that volatile and semi-volatile organic compounds were present. In December 1998, a process test (phase I) was conducted in which the pumps in tanks 241-C-106 and 241-AY-102 were operated and vapor samples obtained to determine constituents that may be present during active sluicing of tank 241-C-106. The process test was suspended when a jumper leak was detected. On March 7, 1999, phase I1 of the process test was performed; the sluicing system was operated for approximately 7 hours and was ended using the controlled shutdown method when the allowable amount of solids were transferred to 241-AY-102. The phase II test was successful, however, further testing is required to obtain vapor samples at higher emission levels

  17. Novel concepts for the compression of large volumes of carbon dioxide-phase III

    Energy Technology Data Exchange (ETDEWEB)

    Moore, J. Jeffrey [Southwest Research Inst., San Antonio, TX (United States); Allison, Timothy C. [Southwest Research Inst., San Antonio, TX (United States); Evans, Neal D. [Southwest Research Inst., San Antonio, TX (United States); Moreland, Brian [Southwest Research Inst., San Antonio, TX (United States); Hernandez, Augusto J. [Southwest Research Inst., San Antonio, TX (United States); Day, Meera [Southwest Research Inst., San Antonio, TX (United States); Ridens, Brandon L. [Southwest Research Inst., San Antonio, TX (United States)

    2014-06-30

    and tested in a closed loop compressor facility using CO2 . Both test programs successfully demonstrated good performance and mechanical behavior. In Phase III, a pilot compression plant consisting of a multi-stage centrifugal compressor with cooled diaphragm technology has been designed, constructed, and tested. Comparative testing of adiabatic and cooled tests at equivalent inlet conditions shows that the cooled diaphragms reduce power consumption by 3-8% when the compressor is operated as a back-to-back unit and by up to 9% when operated as a straight-though compressor with no intercooler. The power savings, heat exchanger effectiveness, and temperature drops for the cooled diaphragm were all slightly higher than predicted values but showed the same trends.

  18. Effects of extracellular and intracellular pH on repair of potentially lethal damage, chromosome aberrations and DNA double-strand breaks in irradiated plateau-phase A549 cells

    International Nuclear Information System (INIS)

    Jayanth, V.R.; Bayne, M.T.; Varnes, M.E.

    1994-01-01

    Plateau-phage A549 cells exhibit a high capacity for repair of potentially lethal radiation damage (PLD). Previously it was found that PLD repair could be partially inhibited by increasing the extracellular pH (pH e ) of the spent medium from its normal value of 6.7-6.8 to 7.6 during postirradiation holding. This study shows that PLD repair is also inhibited by reducing the pH e of the spent medium to 6.0. The effects of altering pH e on rejoining of DNA double-strand breaks (DSBs) as measured by neutral filter elution and on mitotic delay and chromosome aberrations seen after releasing cells from the plateau phase were investigated. Neither increasing nor decreasing the pH e of the spent medium had an effect on radiation-induced mitotic delay. Rejoining of DSBs was significantly inhibited by holding at pH e 6.0 but not affected by holding at pH e 7.6. At 2 h after irradiation about 51% of unrejoined breaks remained at pH e 6.0, compared to about 15% at pH e 6.7 or 7.6. However, holding at pH e 7.6 appeared to cause a marginal change in the kinetics of rejoining of DSBs. Repair of lesions leading to dicentric and acentric chromosome aberrations did not occur when cells were held at pH e 6.0, since less than 10% of these aberrations disappeared from cells held for 24 h before subculture. In contrast, holding plateau-phase cells at pH e 7.6 vs 6.7 caused a small but significant reduction in the disappearance of dicentrics but had no effect on the rate or extent of the disappearance of acentrics. These data have led us to hypothesize that inhibition of PLD repair by holding at pH e 6.0 is related both to inhibition of pH-dependent DNA repair enzymes and to induction of changes in DNA which lead to misrepair when the cells are released from plateau phase. Inhibition of PLD repair by holding at pH e 7.6 is related primarily to changes in DNA structure which promote misrepair. 43 refs., 5 figs., 4 tabs

  19. Analysis of Reasons for fluctuation in seal oil system on generator and countermeasures in Qinshan phase III project

    International Nuclear Information System (INIS)

    Jin Xiaodong

    2012-01-01

    Reasons for hydraulic differential fluctuations seal hydrogen oil on generator in Qinshan phase III project were analyzed, provide a basis for modifying Run method is to determine the causes and effects of seal oil flow changes and in the relationship between flow changes and hydraulic differential hydrogen oil changes according to reason Results were analyzed to adjust the running test, to verify the feasibility of running adjustment programs

  20. Stakeholder perspectives on the use of positron emission tomography in phase III oncology trials in the UK.

    Science.gov (United States)

    Rojas-Anaya, Hector; Skogen, Karoline; Miles, Kenneth Alan

    2012-06-01

    To identify factors that influence the use of PET in phase III oncology trials in the UK by evaluating stakeholder perspectives. A wide range of UK PET research stakeholders with a potential interest in the use of PET in phase III trials were identified and invited to participate. These UK PET research stakeholders were consulted using a semistructured questionnaire on their personal experience with and involvement in PET research, the role of PET in phase III oncology clinical trials and on the promotion of UK PET research and unmet clinical needs in oncology. Responses were analysed quantitatively and by qualitative content analysis of free-text responses. A total of 118 responses were received from a wide range of stakeholders representing several professional groups and working environments. Of these respondents, 49 (42%) were using PET in their research. There was the general perception that using PET in clinical research is beneficial in oncology. The two major barriers identified were poor availability of PET and perceived difficulties in funding of excess treatment costs (75% of respondents). Other factors included limited coverage of PET in training, uncertainty about developing imaging protocols or the status of tracers other than 18F-fluorodeoxyglucose, and low awareness of the role of PET in patient selection for therapeutic trials. Patient concerns about radiation were not perceived as a research barrier. Interventions that improve the availability and funding pathways for PET research scans and that increase researcher awareness could help promote the use of PET for phase III oncology trials in the UK.

  1. High Efficiency Quantum Dot III-V Multijunction Solar Cell for Space Power, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — We are proposing to utilize quantum dots to develop a super high-efficiency multijunction III-V solar cell for space. In metamorphic triple junction space solar...

  2. Twenty-seven years of phase III trials for patients with extensive disease small-cell lung cancer: disappointing results.

    Directory of Open Access Journals (Sweden)

    Isao Oze

    Full Text Available BACKGROUND: Few studies have formally assessed whether treatment outcomes have improved substantially over the years for patients with extensive disease small-cell lung cancer (ED-SCLC enrolled in phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials. METHODS AND FINDINGS: We searched for trials that were reported between January 1981 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated by using a linear regression analysis. RESULTS: In total, 52 trials were identified that had been initiated between 1980 and 2006; these studies involved 10,262 patients with 110 chemotherapy arms. The number of randomized patients and the proportion of patients with good performance status (PS increased over time. Cisplatin-based regimens, especially cisplatin and etoposide (PE regimen, have increasingly been studied, whereas cyclophosphamide, doxorubicin, and vincristine-based regimens have been less investigated. Multiple regression analysis showed no significant improvement in survival over the years. Additionally, the use of a PE regimen did not affect survival, whereas the proportion of patients with good PS and the trial design of assigning prophylactic cranial irradiation were significantly associated with favorable outcome. CONCLUSIONS AND SIGNIFICANCE: The survival of patients with ED-SCLC enrolled in phase III trials did not improve significantly over the years, suggesting the need for further development of novel targets, newer agents, and comprehensive patient care.

  3. Broadband microwave photonic fully tunable filter using a single heterogeneously integrated III-V/SOI-microdisk-based phase shifter.

    Science.gov (United States)

    Lloret, Juan; Morthier, Geert; Ramos, Francisco; Sales, Salvador; Van Thourhout, Dries; Spuesens, Thijs; Olivier, Nicolas; Fédéli, Jean-Marc; Capmany, José

    2012-05-07

    A broadband microwave photonic phase shifter based on a single III-V microdisk resonator heterogeneously integrated on and coupled to a nanophotonic silicon-on-insulator waveguide is reported. The phase shift tunability is accomplished by modifying the effective index through carrier injection. A comprehensive semi-analytical model aiming at predicting its behavior is formulated and confirmed by measurements. Quasi-linear and continuously tunable 2π phase shifts at radiofrequencies greater than 18 GHz are experimentally demonstrated. The phase shifter performance is also evaluated when used as a key element in tunable filtering schemes. Distortion-free and wideband filtering responses with a tuning range of ~100% over the free spectral range are obtained.

  4. 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

  5. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1.

    Science.gov (United States)

    Smith, Matthew; De Bono, Johann; Sternberg, Cora; Le Moulec, Sylvestre; Oudard, Stéphane; De Giorgi, Ugo; Krainer, Michael; Bergman, Andries; Hoelzer, Wolfgang; De Wit, Ronald; Bögemann, Martin; Saad, Fred; Cruciani, Giorgio; Thiery-Vuillemin, Antoine; Feyerabend, Susan; Miller, Kurt; Houédé, Nadine; Hussain, Syed; Lam, Elaine; Polikoff, Jonathan; Stenzl, Arnulf; Mainwaring, Paul; Ramies, David; Hessel, Colin; Weitzman, Aaron; Fizazi, Karim

    2016-09-01

    Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post-random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes. © 2016 by

  6. 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.

  7. Investigation of global particulate nitrate from the AeroCom phase III experiment

    Directory of Open Access Journals (Sweden)

    H. Bian

    2017-11-01

    Full Text Available An assessment of global particulate nitrate and ammonium aerosol based on simulations from nine models participating in the Aerosol Comparisons between Observations and Models (AeroCom phase III study is presented. A budget analysis was conducted to understand the typical magnitude, distribution, and diversity of the aerosols and their precursors among the models. To gain confidence regarding model performance, the model results were evaluated with various observations globally, including ground station measurements over North America, Europe, and east Asia for tracer concentrations and dry and wet depositions, as well as with aircraft measurements in the Northern Hemisphere mid-to-high latitudes for tracer vertical distributions. Given the unique chemical and physical features of the nitrate occurrence, we further investigated the similarity and differentiation among the models by examining (1 the pH-dependent NH3 wet deposition; (2 the nitrate formation via heterogeneous chemistry on the surface of dust and sea salt particles or thermodynamic equilibrium calculation including dust and sea salt ions; and (3 the nitrate coarse-mode fraction (i.e., coarse/total. It is found that HNO3, which is simulated explicitly based on full O3-HOx-NOx-aerosol chemistry by all models, differs by up to a factor of 9 among the models in its global tropospheric burden. This partially contributes to a large difference in NO3−, whose atmospheric burden differs by up to a factor of 13. The atmospheric burdens of NH3 and NH4+ differ by 17 and 4, respectively. Analyses at the process level show that the large diversity in atmospheric burdens of NO3−, NH3, and NH4+ is also related to deposition processes. Wet deposition seems to be the dominant process in determining the diversity in NH3 and NH4+ lifetimes. It is critical to correctly account for contributions of heterogeneous chemical production of nitrate on dust and sea salt, because this process

  8. Radiation therapy for ocular choroidal neovascularization (phase I/II study)

    International Nuclear Information System (INIS)

    Sasai, Keisuke; Murata, Rumi; Mandai, Michiko; Takahashi, Masayo; Hiraoka, Masahiro

    1996-01-01

    Purpose/Objective: Choroidal neovascularization (CNV) is a major cause of severe loss of visual acuity in some ocular diseases such as age-related macular degeneration (ARMD) and angio-streaks. Laser photocoagulation has been used to treat patients with subfoveal neovascular lesions with well demarcated boundaries. However, the treatment method is usually associated with a large decrease in visual acuity. Therefore, indications for this treatment are very limited. Recently, some investigators reported the effect of low dose irradiation on the subretinal neovascular membranes in CNV. We conducted a phase I/II study to determine the toxicity and efficacy of external photon beam radiotherapy in patients with CNV. Materials and Methods: Between April 1994 and July 1995, 36 patients with choroidal neovascularization (34 with ARMD; 2 with angiostreaks) were treated with radiation therapy. Eligibility criteria for this study were as follows: the eyes had subretinal neovascular membranes in the avascular area of the fovea; the neovascular membranes had grown in size in the last 6 months; the best pretreatment corrected visual acuity was worse than (20(25)); there were no large subretinal hemorrhages causing decrease in visual acuity; patients were 50 years or older and had not received laser photocoagulation nor other treatment for this condition. Written informed consent was obtained from all patients. The patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Fluorescein angiography, measurement of the best corrected visual acuity, ophthalmoscopic and biomicroscopic examinations were performed at 1, 3, 6, and 12 months after treatment. Treatment planning was performed using a CT simulator which enables real-time treatment planning from multiple CT slices. The clinical target volume included the macula and optic disc, which received a dose of 10 Gy/5 fractions/1 week (first 18 eyes) or 20 Gy/10 fractions

  9. Neighborhood crime and transit station access mode choice - phase III of neighborhood crime and travel behavior.

    Science.gov (United States)

    2015-08-01

    This report provides the findings from the third phase of a three-part study about the influences of neighborhood crimes on travel : mode choice. While previous phases found evidence that high levels of neighborhood crime discourage people from choos...

  10. Tibial Plateau Fractures

    DEFF Research Database (Denmark)

    Elsøe, Rasmus

    This PhD thesis reported an incidence of tibial plateau fractures of 10.3/100,000/year in a complete Danish regional population. The results reported that patients treated for a lateral tibial plateau fracture with bone tamp reduction and percutaneous screw fixation achieved a satisfactory level...... with only the subgroup Sport significantly below the age matched reference population. The thesis reports a level of health related quality of life (Eq5d) and disability (KOOS) significantly below established reference populations for patients with bicondylar tibial plateau fracture treated with a ring...... fixator, both during treatment and at 19 months following injury. In general, the thesis demonstrates that the treatment of tibial plateau fractures are challenging and that some disabilities following these fractures must be expected. Moreover, the need for further research in the area, both with regard...

  11. Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

    Science.gov (United States)

    Takahashi, Fumihiro; Morita, Satoshi

    2018-02-08

    Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

  12. The costs and effectiveness of large Phase III pre-licensure vaccine clinical trials.

    Science.gov (United States)

    Black, Steven

    2015-01-01

    Prior to the 1980s, most vaccines were licensed based upon safety and effectiveness studies in several hundred individuals. Beginning with the evaluation of Haemophilus influenzae type b conjugate vaccines, much larger pre-licensure trials became common. The pre-licensure trial for Haemophilus influenzae oligosaccharide conjugate vaccine had more than 60,000 children and that of the seven-valent pneumococcal conjugate vaccine included almost 38,000 children. Although trial sizes for both of these studies were driven by the sample size required to demonstrate efficacy, the sample size requirements for safety evaluations of other vaccines have subsequently increased. With the demonstration of an increased risk of intussusception following the Rotashield brand rotavirus vaccine, this trend has continued. However, routinely requiring safety studies of 20,000-50,000 or more participants has two major downsides. First, the cost of performing large safety trials routinely prior to licensure of a vaccine is very large, with some estimates as high at US$200 million euros for one vaccine. This high financial cost engenders an opportunity cost whereby the number of vaccines that a company is willing or able to develop to meet public health needs becomes limited by this financial barrier. The second downside is that in the pre-licensure setting, such studies are very time consuming and delay the availability of a beneficial vaccine substantially. One might argue that in some situations, this financial commitment is warranted such as for evaluations of the risk of intussusception following newer rotavirus vaccines. However, it must be noted that while an increased risk of intussusception was not identified in large pre-licensure studies, in post marketing evaluations an increased risk of this outcome has been identified. Thus, even the extensive pre-licensure evaluations conducted did not identify an associated risk. The limitations of large Phase III trials have also been

  13. Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma

    DEFF Research Database (Denmark)

    Geoerger, Birgit; Bergeron, Christophe; Gore, Lia

    2017-01-01

    BACKGROUND: Ipilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available. METHODS: Patients aged 12 to <18 years with previously treated or untreated, unresectable stage III or IV mal...

  14. Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

    Science.gov (United States)

    2017-11-15

    Hurler Syndrome (MPS I); Hurler-Scheie Syndrome; Hunter Syndrome (MPS II); Sanfilippo Syndrome (MPS III); Krabbe Disease (Globoid Leukodystrophy); Metachromatic Leukodystrophy (MLD); Adrenoleukodystrophy (ALD and AMN); Sandhoff Disease; Tay Sachs Disease; Pelizaeus Merzbacher (PMD); Niemann-Pick Disease; Alpha-mannosidosis

  15. Enhanced Cr(VI) reduction and As(III) oxidation in ice phase: Important role of dissolved organic matter from biochar

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Xiaoling [Department of Soil and Water Science, University of Florida, Gainesville, FL 32611 (United States); Ma, Lena Q., E-mail: lqma@ufl.edu [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Jiangsu 210046 (China); Department of Soil and Water Science, University of Florida, Gainesville, FL 32611 (United States); Gress, Julia; Harris, Willie [Department of Soil and Water Science, University of Florida, Gainesville, FL 32611 (United States); Li, Yuncong [Soil and Water Science Department, Tropical Research and Education Center, University of Florida, Homestead, FL 33031-3314 (United States)

    2014-02-01

    Graphical abstract: - Highlights: • Biochar-derived dissolved organic matter (DOM) effectively reduced Cr(VI) and oxidized As(III). • Cr(VI) and As(III) could serve as a redox couple. • Cr(VI) and As(III) redox conversion was more effective in the ice phase than aqueous phase. • FTIR and ESR showed that biochar DOM served as both electron donor and acceptor. - Abstract: This study evaluated the impact of DOM from two biochars (sugar beet tailing and Brazilian pepper) on Cr(VI) reduction and As(III) oxidation in both ice and aqueous phases with a soil DOM as control. Increasing DOM concentration from 3 to 300 mg C L{sup −1} enhanced Cr(VI) reduction from 20% to 100% and As(III) oxidation from 6.2% to 25%; however, Cr(VI) reduction decreased from 80–86% to negligible while As(III) oxidation increased from negligible to 18–19% with increasing pH from 2 to 10. Electron spin resonance study suggested semiquinone radicals in DOM were involved in As(III) oxidation while Fourier transform infrared analysis suggested that carboxylic groups in DOM participated in both Cr(VI) reduction and As(III) oxidation. During Cr(VI) reduction, part of DOM (∼10%) was oxidized to CO{sub 2}. The enhanced conversion of Cr(VI) and As(III) in the ice phase was due to the freeze concentration effect with elevated concentrations of electron donors and electron acceptors in the grain boundary. Though DOM enhanced both Cr(VI) reduction and As(III)oxidation, Cr(VI) reduction coupled with As(III) oxidation occurred in absence of DOM. The role of DOM, Cr(VI) and/or As(III) in Cr and As transformation may provide new insights into their speciation and toxicity in cold regions.

  16. Phasing-in Basel III capital and liquidity requirements in post-revolution Egypt

    Directory of Open Access Journals (Sweden)

    Monal Abdel-Baki

    2012-08-01

    Full Text Available The Basel Committee has introduced a new set of capital and liquidity requirements to be introduced by the global banking system during 2013 till January 2019. Egypt possesses a well-capitalised banking sector, yet it has been exposed to the devastating shock imposed by its popular revolution. Using the GMM method, the impact of introducing the new capital and liquidity requirements on the macroeconomic performance of the Egyptian economy is examined. The results reveal that Egyptian banks are motivated to enhance capital and liquidity ratios in the case of realizing high profits and favourable conditions at the individual banking level. On the other hand, negative macroeconomic performance and a poor business environment substantially deter the preparedness of Egyptian banks to meet the Basel III requirements. The analysis is timely given the need for compliance with Basel III as one of the requirements to raise the credit rating of the devastated economy.

  17. Baseline job satisfaction and stress among pharmacists and pharmacy technicians participating in the Fleetwood Phase III Study.

    Science.gov (United States)

    Lapane, Kate L; Hughes, Carmel M

    2004-11-01

    To provide baseline levels of job satisfaction and stress among members of the long-term care pharmacy team participating in the Fleetwood Phase III evaluation. Cross-sectional design; long-term care pharmacy provider in North Carolina (the implementation site of the large-scale Fleetwood Phase III study). All current pharmacy employees as of May/June 2002. None. Health Professional Stress Inventory and job satisfaction. Ninety-four percent (16/17) of consultant pharmacists were satisfied with their job, with 89% reporting they would definitely choose to be a pharmacist again. Seventy-five percent both of dispensing pharmacists and pharmacy technicians reported overall job satisfaction. Forty-one reported that they would not choose to be a pharmacist (pharmacy technician) again. The most frequently reported sources of stress among the dispensing pharmacists and pharmacy technicians were conflicts with non-work obligations (i.e., family, personal life) and the ability to perform duties with short staffing. In addition, inadequate pay and few opportunities for job advancement were often/frequent sources of stress among pharmacy technicians. More than one third of dispensing pharmacists also reported stress frequently because of fears of mistakes in patient treatment. Overall, consultants are very satisfied with their positions, although dispensing pharmacists and pharmacy technicians are less satisfied with their work. The reasons may be because of the different nature of each job, as well as staffing shortages. The extent to which the Fleetwood Model can improve job satisfaction and impact on stress will be evaluated once we resurvey the pharmacy team after the intervention period of the Fleetwood Phase III study.

  18. Evaluation of DCS III Transmission Alternatives. Phase 1A report. Appendix B. Regulatory Barriers.

    Science.gov (United States)

    1980-05-26

    Resolution DK). B.1.1.5 Importance of the RR in the DCS III Study. The ITU Radio Regulation offers a means to appraise viability of the alternatives to be...interference 466-1 483 Measurement of performance by means of signal 482 Measurement of noise in actual traffic 481 Table B.l-6. Communication Satellite...Economic and technical aspects of the choice of transmission systems GAS 5 Economic conditions and tel ecommunication development GAS 6 Economic and

  19. Zirconium metal-water oxidation kinetics. III. Oxygen diffusion in oxide and alpha Zircaloy phases

    International Nuclear Information System (INIS)

    Pawel, R.E.

    1976-10-01

    The reaction of Zircaloy in steam at elevated temperature involves the growth of discrete layers of oxide and oxygen-rich alpha Zircaloy from the parent beta phase. The multiphase, moving boundary diffusion problem involved is encountered in a number of important reaction schemes in addition to that of Zircaloy-oxygen and can be completely (albeitly ideally) characterized through an appropriate model in terms of oxygen diffusion coefficients and equilibrium concentrations for the various phases. Conversely, kinetic data for phase growth and total oxygen consumption rates can be used to compute diffusion coefficients. Equations are developed that express the oxygen diffusion coefficients in the oxide and alpha phases in terms of the reaction rate constants and equilibrium solubility values. These equations were applied to recent experimental kinetic data on the steam oxidation of Zircaloy-4 to determine the effective oxygen diffusion coefficients in these phases over the temperature range 1000--1500 0 C

  20. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

    Science.gov (United States)

    Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

    2016-04-01

    Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

  1. Inter-machine comparison of the termination phase and energy conversion in tokamak disruptions with runaway current plateau formation and implications for ITER

    International Nuclear Information System (INIS)

    Martín-Solís, J.R.; Loarte, A.; Hollmann, E.M.; Esposito, B.; Riccardo, V.

    2014-01-01

    The termination of the current and the loss of runaway electrons following runaway current plateau formation during disruptions have been investigated in the JET, DIII-D and FTU tokamaks. Substantial conversion of magnetic energy into runaway kinetic energy, up to ∼10 times the initial plateau runaway kinetic energy, has been inferred for the slowest current terminations. Both modelling and experiment suggest that, in present devices, the efficiency of conversion into runaway kinetic energy is determined to a great extent by the characteristic runaway loss time, τ diff , and the resistive time of the residual ohmic plasma after the disruption, τ res , increasing with the ratio τ diff /τ res . It is predicted that, in large future devices such as ITER, the generation of runaways by the avalanche mechanism will play an important role, particularly for slow runaway discharge terminations, increasing substantially the amount of energy deposited by the runaways onto the plasma-facing components by the conversion of magnetic energy of the runaway plasma into runaway kinetic energy. Estimates of the power fluxes on the beryllium plasma-facing components during runaway termination in ITER indicate that for runaway currents of up to 2 MA no melting of the components is expected. For larger runaway currents, minimization of the effects of runaway impact on the first wall requires a reduction in the kinetic energy of the runaway beam before termination and, in addition, high plasma density n e and low ohmic plasma resistance (long τ res ) to prevent large conversion of magnetic into runaway kinetic energy during slow current terminations. (paper)

  2. Chromospheric oscillations observed with OSO 8. III. Average phase spectra for Si II

    International Nuclear Information System (INIS)

    White, O.R.; Athay, R.G.

    1979-01-01

    Time series of intensity and Doppler-shift fluctuations in the Si II emission lines lambda816.93 and lambda817.45 are Fourier analyzed to determine the frequency variation of phase differences between intensity and velocity and between these two lines formed 300 km apart in the middle chromosphere. Average phase spectra show that oscillations between 2 and 9 mHz in the two lines have time delays from 35 to 40 s, which is consistent with the upward propagation of sound wave at 8.6-7.5 km s -1 . In this same frequency band near 3 mHz, maximum brightness leads maximum blueshift by 60 0 . At frequencies above 11 mHz where the power spectrum is flat, the phase differences are uncertain, but approximately 65% of the cases indicate upward propagation. At these higher frequencies, the phase lead between intensity and blue Doppler shift ranges from 0 0 to 180 0 with an average value of 90 0 . However, the phase estimates in this upper band are corrupted by both aliasing and randomness inherent to the measured signals. Phase differences in the two narrow spectral features seen at 10.5 and 27 mHz in the power spectra are shown to be consistent with properties expected for aliases of the wheel rotation rate of the spacecraft wheel section

  3. Air quality and climate change, Topic 3 of the Model Inter-Comparison Study for Asia Phase III (MICS-Asia III) - Part 1: Overview and model evaluation

    Science.gov (United States)

    Gao, Meng; Han, Zhiwei; Liu, Zirui; Li, Meng; Xin, Jinyuan; Tao, Zhining; Li, Jiawei; Kang, Jeong-Eon; Huang, Kan; Dong, Xinyi; Zhuang, Bingliang; Li, Shu; Ge, Baozhu; Wu, Qizhong; Cheng, Yafang; Wang, Yuesi; Lee, Hyo-Jung; Kim, Cheol-Hee; Fu, Joshua S.; Wang, Tijian; Chin, Mian; Woo, Jung-Hun; Zhang, Qiang; Wang, Zifa; Carmichael, Gregory R.

    2018-04-01

    Topic 3 of the Model Inter-Comparison Study for Asia (MICS-Asia) Phase III examines how online coupled air quality models perform in simulating high aerosol pollution in the North China Plain region during wintertime haze events and evaluates the importance of aerosol radiative and microphysical feedbacks. A comprehensive overview of the MICS-Asia III Topic 3 study design, including descriptions of participating models and model inputs, the experimental designs, and results of model evaluation, are presented. Six modeling groups from China, Korea and the United States submitted results from seven applications of online coupled chemistry-meteorology models. Results are compared to meteorology and air quality measurements, including data from the Campaign on Atmospheric Aerosol Research Network of China (CARE-China) and the Acid Deposition Monitoring Network in East Asia (EANET). The correlation coefficients between the multi-model ensemble mean and the CARE-China observed near-surface air pollutants range from 0.51 to 0.94 (0.51 for ozone and 0.94 for PM2.5) for January 2010. However, large discrepancies exist between simulated aerosol chemical compositions from different models. The coefficient of variation (SD divided by the mean) can reach above 1.3 for sulfate in Beijing and above 1.6 for nitrate and organic aerosols in coastal regions, indicating that these compositions are less consistent from different models. During clean periods, simulated aerosol optical depths (AODs) from different models are similar, but peak values differ during severe haze events, which can be explained by the differences in simulated inorganic aerosol concentrations and the hygroscopic growth efficiency (affected by varied relative humidity). These differences in composition and AOD suggest that future models can be improved by including new heterogeneous or aqueous pathways for sulfate and nitrate formation under hazy conditions, a secondary organic aerosol (SOA) formation chemical

  4. Coping with missing data in phase III pivotal registration trials: Tolvaptan in subjects with kidney disease, a case study.

    Science.gov (United States)

    Ouyang, John; Carroll, Kevin J; Koch, Gary; Li, Junfang

    2017-07-01

    Missing data cause challenging issues, particularly in phase III registration trials, as highlighted by the European Medicines Agency (EMA) and the US National Research Council. We explore, as a case study, how the issues from missing data were tackled in a double-blind phase III trial in subjects with autosomal dominant polycystic kidney disease. A total of 1445 subjects were randomized in a 2:1 ratio to receive active treatment (tolvaptan), or placebo. The primary outcome, the rate of change in total kidney volume, favored tolvaptan (P outline the analyses undertaken to address the issue of missing data thoroughly. "Tipping point analyses" were performed to explore how extreme and detrimental outcomes among subjects with missing data must be to overturn the positive treatment effect attained in those subjects who had complete data. Nonparametric rank-based analyses were also performed accounting for missing data. In conclusion, straightforward and transparent analyses directly taking into account missing data convincingly support the robustness of the preplanned analyses on the primary and secondary endpoints. Tolvaptan was confirmed to be effective in slowing total kidney volume growth, which is considered an efficacy endpoint by EMA, and in lessening the decline in renal function in patients with autosomal dominant polycystic kidney disease. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Predicting hypothetical willingness to participate (WTP) in a future phase III HIV vaccine trial among high-risk adolescents.

    Science.gov (United States)

    Giocos, Georgina; Kagee, Ashraf; Swartz, Leslie

    2008-11-01

    The present study sought to determine whether the Theory of Planned Behaviour predicted stated hypothetical willingness to participate (WTP) in future Phase III HIV vaccine trials among South African adolescents. Hierarchical logistic regression analyses showed that The Theory of Planned Behaviour (TPB) significantly predicted WTP. Of all the predictors, Subjective norms significantly predicted WTP (OR = 1.19, 95% C.I. = 1.06-1.34). A stepwise logistic regression analysis revealed that Subjective Norms (OR = 1.19, 95% C.I. = 1.07-1.34) and Attitude towards participation in an HIV vaccine trial (OR = 1.32, 95% C.I. = 1.00-1.74) were significant predictors of WTP. The addition of Knowledge of HIV vaccines and HIV vaccine trials, Perceived self-risk of HIV infection, Health-promoting behaviours and Attitudes towards HIV/AIDS yielded non-significant results. These findings provide support for the Theory of Reasoned Action (TRA) and suggest that psychosocial factors may play an important role in WTP in Phase III HIV vaccine trials among adolescents.

  6. Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer

    International Nuclear Information System (INIS)

    Inoue, Takehiro; Inoue, Toshihiko; Yoshida, Ken; Yoshioka, Yasuo; Shimamoto, Shigetoshi; Tanaka, Eiichi; Yamazaki, Hideya; Shimizutani, Kimishige; Teshima, Teruki; Furukawa, Souhei

    2001-01-01

    Purpose: Early mobile tongue cancer can be controlled with interstitial radiotherapy (ISRT). We carried out a Phase III trial to compare the treatment results of low-dose-rate (Ld) ISRT and high-dose-rate (HDR) ISRT for early mobile tongue cancer. Methods and Materials: From April 1992 through October 1996, 59 patients with cancer of the early mobile tongue were registered in this Phase III study. Eight patients were excluded from the evaluation because of violations of the requirements for this study. Of 51 eligible patients, 26 patients were treated with LDR-ISRT (70 Gy/4-9 days) and 25 patients with HDR-ISRT (60 Gy/10 fractions/1 week). For the hyperfractionated HDR-ISRT, the time interval between 2 fractions was more than 6 h. Results: Five-year local control rates of the LDR and HDR groups were 84% and 87% respectively. Nodal metastasis occurred in 6 patients in each group. Five-year nodal control rates of the LDR and HDR groups were 77% and 76%, respectively. Conclusion: Hyperfractionated HDR-ISRT for early mobile tongue cancer has the same local control compared with continuous LDR-ISRT. Hyperfractionated HDR-ISRT is an alternative treatment for continuous LDR-ISRT

  7. Novel solid phase extraction procedure for gold(III) on Dowex M 4195 prior to its flame atomic absorption spectrometric determination

    International Nuclear Information System (INIS)

    Tuzen, Mustafa; Saygi, Kadriye O.; Soylak, Mustafa

    2008-01-01

    A method for solid phase extraction (SPE) of gold(III) using Dowex M 4195 chelating resin has been developed. The optimum experimental conditions for the quantitative sorption of gold(III), pH, effect of flow rates, eluent types, sorption capacity and the effect of diverse ions on the sorption of gold(III) have been investigated. The chelating resin can be reused for more than 100 cycles of sorption-desorption without any significant change in sorption of gold(III) ions. The recovery values for gold(III) and detection limit (LOD) of gold were greater than 95% and 1.61 μg L -1 , respectively. The preconcentration factor was 31. The relative standard deviation of the method was -1 . The proposed method has been applied for the determination of gold(III) in some real samples including water, soil and sediment samples

  8. First-principles interatomic potentials for transition-metal aluminides. III. Extension to ternary phase diagrams

    International Nuclear Information System (INIS)

    Widom, Mike; Al-Lehyani, Ibrahim; Moriarty, John A.

    2000-01-01

    Modeling structural and mechanical properties of intermetallic compounds and alloys requires detailed knowledge of their interatomic interactions. The first two papers of this series [Phys. Rev. B 56, 7905 (1997); 58, 8967 (1998)] derived first-principles interatomic potentials for transition-metal (TM) aluminides using generalized pseudopotential theory (GPT). Those papers focused on binary alloys of aluminum with first-row transition metals and assessed the ability of GPT potentials to reproduce and elucidate the alloy phase diagrams of Al-Co and Al-Ni. This paper addresses the phase diagrams of the binary alloy Al-Cu and the ternary systems Al-Co-Cu and Al-Co-Ni, using GPT pair potentials calculated in the limit of vanishing transition-metal concentration. Despite this highly simplifying approximation, we find rough agreement with the known low-temperature phase diagrams, up to 50% total TM concentration provided the Co fraction is below 25%. Full composition-dependent potentials and many-body interactions would be required to correct deficiencies at higher Co concentration. Outside this troublesome region, the experimentally determined stable and metastable phases all lie on or near the convex hull of a scatter plot of energy versus composition. We verify, qualitatively, reported solubility ranges extending binary alloys into the ternary diagram in both Al-Co-Cu and Al-Co-Ni. Finally, we reproduce previously conjectured transition-metal positions in the decagonal quasicrystal phase. (c) 2000 The American Physical Society

  9. First-principles interatomic potentials for transition-metal aluminides. III. Extension to ternary phase diagrams

    Science.gov (United States)

    Widom, Mike; Al-Lehyani, Ibrahim; Moriarty, John A.

    2000-08-01

    Modeling structural and mechanical properties of intermetallic compounds and alloys requires detailed knowledge of their interatomic interactions. The first two papers of this series [Phys. Rev. B 56, 7905 (1997); 58, 8967 (1998)] derived first-principles interatomic potentials for transition-metal (TM) aluminides using generalized pseudopotential theory (GPT). Those papers focused on binary alloys of aluminum with first-row transition metals and assessed the ability of GPT potentials to reproduce and elucidate the alloy phase diagrams of Al-Co and Al-Ni. This paper addresses the phase diagrams of the binary alloy Al-Cu and the ternary systems Al-Co-Cu and Al-Co-Ni, using GPT pair potentials calculated in the limit of vanishing transition-metal concentration. Despite this highly simplifying approximation, we find rough agreement with the known low-temperature phase diagrams, up to 50% total TM concentration provided the Co fraction is below 25%. Full composition-dependent potentials and many-body interactions would be required to correct deficiencies at higher Co concentration. Outside this troublesome region, the experimentally determined stable and metastable phases all lie on or near the convex hull of a scatter plot of energy versus composition. We verify, qualitatively, reported solubility ranges extending binary alloys into the ternary diagram in both Al-Co-Cu and Al-Co-Ni. Finally, we reproduce previously conjectured transition-metal positions in the decagonal quasicrystal phase.

  10. Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting

    Directory of Open Access Journals (Sweden)

    van der Meijde Jolanda

    2007-08-01

    Full Text Available Abstract Background Fasting has dramatic effects on small intestinal transport function. However, little is known on expression of intestinal transport and phase I/II metabolism genes during fasting and the role the fatty acid-activated transcription factor PPARα may play herein. We therefore investigated the effects of fasting on expression of these genes using Affymetrix GeneChip MOE430A arrays and quantitative RT-PCR. Results After 24 hours of fasting, expression levels of 33 of the 253 analyzed transporter and phase I/II metabolism genes were changed. Upregulated genes were involved in transport of energy-yielding molecules in processes such as glycogenolysis (G6pt1 and mitochondrial and peroxisomal oxidation of fatty acids (Cact, Mrs3/4, Fatp2, Cyp4a10, Cyp4b1. Other induced genes were responsible for the inactivation of the neurotransmitter serotonin (Sert, Sult1d1, Dtd, Papst2, formation of eicosanoids (Cyp2j6, Cyp4a10, Cyp4b1, or for secretion of cholesterol (Abca1 and Abcg8. Cyp3a11, typically known because of its drug metabolizing capacity, was also increased. Fasting had no pronounced effect on expression of phase II metabolic enzymes, except for glutathione S-transferases which were down-regulated. Time course studies revealed that some genes were acutely regulated, whereas expression of other genes was only affected after prolonged fasting. Finally, we identified 8 genes that were PPARα-dependently upregulated upon fasting. Conclusion We have characterized the response to fasting on expression of transporters and phase I/II metabolic enzymes in murine small intestine. Differentially expressed genes are involved in a variety of processes, which functionally can be summarized as a increased oxidation of fat and xenobiotics, b increased cholesterol secretion, c increased susceptibility to electrophilic stressors, and d reduced intestinal motility. This knowledge increases our understanding of gut physiology, and may be of relevance

  11. Solid phase extraction of Am(III) and Cm(III) from acidic feeds using tetraethyl diglycolamide (TEDGA) in ionic liquid

    NARCIS (Netherlands)

    Gujar, R.B.; Ansari, S.A.; Mohapatra, P.K.; Leoncini, Andrea; Verboom, Willem

    2016-01-01

    Solvent extraction of Am(III) and Cm(III) with several diglycolamide ligands in an ionic liquid, [C4mim][Tf2N] was investigated from nitric acid medium. Based on the encouraging extraction behaviour with N,N,N′,N′-tetraethyldiglycolamide (TEDGA), extraction chromatographic studies were carried out

  12. Phase I/II trial of concurrent use of S-1 and radiation therapy for T2 glottic cancer

    International Nuclear Information System (INIS)

    Nakayama, Meijin; Hayakawa, Kazushige; Okamoto, Makito; Niibe, Yuzuru; Ishiyama, Hiromichi; Kotani, Shouko

    2010-01-01

    A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events. In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m 2 , for a total daily dose of 80 mg/m 2 . The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation. Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2). The use of S-1 at 80 mg/m 2 per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life. (author)

  13. Engineering development of coal-fired high performance power systems, Phase II and III

    Energy Technology Data Exchange (ETDEWEB)

    None

    1999-04-01

    The goals of the program are to develop a coal-fired high performance power generation system (HIPPS) that is capable of: thermal efficiency (HHV) {ge} 47%, NOx, SOx, and particulates {le} 10% NSPS (New Source Performance Standard) coal providing {ge} 65% of heat input, all solid wastes benign, and cost of electricity {le} 90% of present plants. Phase 1, which began in 1992, focused on the analysis of various configurations of indirectly fired cycles and on technical assessments of alternative plant subsystems and components, including performance requirements, developmental status, design options, complexity and reliability, and capital and operating costs. Phase 1 also included preliminary R and D and the preparation of designs for HIPPS commercial plants approximately 300 MWe in size. This phase, Phase 2, involves the development and testing of plant subsystems, refinement and updating of the HIPPS commercial plant design, and the site selection and engineering design of a HIPPS prototype plant. Work reported herein is from: Task 2.1 HITAC Combustors; Task 2.2 HITAF Air Heaters; Task 6 HIPPS Commercial Plant Design Update.

  14. Evidence for the induction of two types of potentially lethal damage after exposure of plateau phase Chinese hamster V79 cells to γ-rays

    International Nuclear Information System (INIS)

    Iliakis, G.

    1985-01-01

    The fixation of γ-rays induced potentially damage (PLD) caused after treatment either with β-araA or in medium made hypertonic by the addition of sodium chloride was studied in plateauphase chinese hamster V79 cells. Treatment with β-araA was found to affect a sector of PLD, the fixation of which specifically reduced the shoulder width of the survival curve. The effect was maximized when cell survival reached levels corresponding to an exponential line, with a slope similar to the final slope of the survival curve of untreated cells. This effect was achieved by a four hour treatment with β-araA at concentrations above 150 μM. Longer treatment times or incubation at higher β-araA concentrations did not significantly enhance the effect. Treatment in hypertonic medium, on the other hand, enhanced cell killing in a concentration dependent (NaCl-concentration) way and the survival reached values much lower than those corresponding to an exponential line. No indication for a plateau in the effect, indicating complete fixation of the sector of PLD that reacts sensitively to this treatment, was obtained. Boht the slope and the shoulder width of the survival curve were affected, the slope first being increaseed after short treatment times (up to 10 min), followed by a decrease in the shoulder width after longer treatment times (longer than 10 min). (orig./WL)

  15. Photoluminescence Polarization Anisotropy in a Single Heterostructured III-V Nanowire with Mixed Crystal Phases

    International Nuclear Information System (INIS)

    Moses, A. F.; Hoang, T. B.; Ahtapodov, L.; Dheeraj, D. L.; Fimland, B. O.; Weman, H.; Helvoort, A. T. J. van

    2011-01-01

    Low temperature (10 K) micro-photoluminescence (μ-PL) of single GaAs/AlGaAs core-shell nanowires with single GaAsSb inserts were measured. The PL emission from the zinc blende GaAsSb insert is strongly polarized along the nanowire axis while the PL emission from the wurtzite GaAs nanowire is perpendiculary polarized to the nanowire axis. The result indicates that the crystal phase, through the optical selection rules, has significant effect on the polarization of the PL from NWs besides the dielectric mismatch. The analysis of the PL results based on the electronic structure of these nanowires supports the correlation between the crystal phase and the PL emission.

  16. Hysteroscopic Essure Inserts for Permanent Contraception: Extended Follow-Up Results of a Phase III Multicenter International Study.

    Science.gov (United States)

    Chudnoff, Scott G; Nichols, John E; Levie, Mark

    2015-01-01

    To describe safety, tolerability, and effectiveness results through 5 years of follow-up of a Phase III trial with Essure inserts. Multicenter, nonrandomized, single-arm international study (Canadian Task Force classification II-3). Thirteen clinical study centers in the United States, Europe, and Australia. A total of 518 previously fertile women seeking permanent contraception. The objective of the hysteroscopic sterilization procedure was bilateral Essure insert placement (ESS205 model) and tubal occlusion. Women with satisfactory device location and tube occlusion (based on modified hysterosalpingography [HSG]) were instructed to discontinue alternative contraception and to rely on Essure inserts for permanent contraception. The primary endpoint for the Phase III study was the rate of pregnancies occurring during the first year of relying (i.e., HSG-confirmed occlusion) on the Essure inserts for permanent contraception (i.e., 12 months after HSG). For the full 5 years of follow-up (5 years total of relying on the Essure inserts for contraception), the endpoints of interest were safety, prevention of pregnancy, and satisfaction. No pregnancies were reported among women relying on the Essure inserts who completed the full 5 years of follow-up. As of December 5, 2007, 449 women with successful bilateral placement relying on the Essure inserts contributed a total 24 942 woman-months of follow-up for assessing effectiveness. Overall, the Essure inserts were generally well tolerated, with participant comfort rated as "good" to "excellent" by 99% of women (382 of 385) after 5 years of use. Similarly, overall satisfaction was rated as "somewhat" to "very satisfied" by 98% of women (376 of 384) after 5 years of use. The majority of adverse events reported during the 5 years of follow-up were rated as either "mild" or "moderate" in severity. Three severe events (abdominal pain with very heavy periods and irregular menstrual bleeding) were reported in 2 subjects during

  17. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    International Nuclear Information System (INIS)

    Huijts, Charlotte M; Santegoets, Saskia J; Eertwegh, Alfons J van den; Pijpers, Laura S; Haanen, John B; Gruijl, Tanja D de; Verheul, Henk M; Vliet, Hans J van der

    2011-01-01

    For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell

  18. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

    Directory of Open Access Journals (Sweden)

    Huijts Charlotte M

    2011-11-01

    Full Text Available Abstract Background For patients with metastatic renal cell cancer (mRCC who progressed on vascular endothelial growth factor (VEGF receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. Methods/design This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part. In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. Discussion This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus

  19. 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.

  20. 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

  1. High-pressure single-crystal elasticity study of CO{sub 2} across phase I-III transition

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jin S., E-mail: zhang72@illinois.edu; Bass, Jay D. [Department of Geology, University of Illinois, Urbana-Champaign, Illinois 61801 (United States); Shieh, Sean R. [Departments of Earth Sciences and Physics and Astronomy, University of Western Ontario, London, Ontario N6A 5B7 (Canada); Dera, Przemyslaw [Hawaii Institute of Geophysics and Planetology, University of Hawaii at Manoa, Honolulu, Hawaii 96822 (United States); Prakapenka, Vitali [Center for Advanced Radiation Sources, University of Chicago, Chicago, Illinois 60637 (United States)

    2014-04-07

    Sound velocities and elastic moduli of solid single-crystal CO{sub 2} were measured at pressures up to 11.7(3) GPa by Brillouin spectroscopy. The aggregate adiabatic bulk modulus (K{sub S}), shear modulus (G), and their pressure derivatives for CO{sub 2} Phase I are K{sub S0} = 3.4(6) GPa, G{sub 0} = 1.8(2) GPa, (dK{sub S}/dP){sub 0} = 7.8(3), (dG/dP){sub 0} = 2.5(1), (d{sup 2}K{sub S}/dP{sup 2}){sub 0} = −0.23(3) GPa{sup −1}, and (d{sup 2}G/dP{sup 2}){sub 0} = −0.10(1) GPa{sup −1}. A small increase of elastic properties was observed between 9.8(1) and 10.5(3) GPa, in agreement with the CO{sub 2} I-III transition pressure determined from previous x-ray diffraction experiments. Above the transition pressure P{sub T}, we observed a mixture dominated by CO{sub 2}-I, with minor CO{sub 2}-III. The CO{sub 2}-I + III mixture shows slightly increased sound velocities compared to pure CO{sub 2}-I. Elastic anisotropy calculated from the single-crystal elasticity tensor exhibits a decrease with pressure beginning at 7.9(1) GPa, which is lower than P{sub T}. Our results coincide with recent X-ray Raman observations, suggesting that a pressure-induced electronic transition is related to local structural and optical changes.

  2. Liquid-liquid extraction of ruthenium(III) thiocyanate with hexamethylphosphoramide: direct spectrophotometric determination in the organic phase

    International Nuclear Information System (INIS)

    Mitra, B.K.; Pal, B.K.; Chowdhury, R.P.

    1982-01-01

    Ru(III) thiocyanate has been extracted with hexamethylphosphoramide(HMPA) in methyl isobutyl ketone (MIBK). Thus the extractability, sensitivity and selectivity are improved over the simple binary Ru(III) thiocyanate system in spectrophotometric determination of ruthenium in the organic phase. The maximum colour develops on the steam bath, at the acidity range of 1.5 - 2.5 M with HCl and ammonium thiocyanate concentration range of 0.25 - O.5 M. The colour is completely extractable in MIBK when 1.5 - 3.0 ml HMPA is used and show maximum absorbance at 570 nm. The colour system obeys Beer's law for 0.7 - 13 μg Ru/ml and the optimum concentration range is 2 - 13 μg/ml. The molar absorptivity and sensitivity are 6940 l . mole -1 cm -1 and 0.0145 μg/cm 2 respectively. The percent relative error is 2.72%. The method is very simple and does not require oxidation and subsequent distillation. The method can be applied in the presence of osmium. (Author)

  3. BEMUSE Phase III Report - Uncertainty and Sensitivity Analysis of the LOFT L2-5 Test

    International Nuclear Information System (INIS)

    Bazin, P.; Crecy, A. de; Glaeser, H.; Skorek, T.; Joucla, J.; Probst, P.; Chung, B.; Oh, D.Y.; Kyncl, M.; Pernica, R.; Macek, J.; Meca, R.; Macian, R.; D'Auria, F.; Petruzzi, A.; Perez, M.; Reventos, F.; Fujioka, K.

    2007-02-01

    This report summarises the various contributions (ten participants) for phase 3 of BEMUSE: Uncertainty and Sensitivity Analyses of the LOFT L2-5 experiment, a Large-Break Loss-of-Coolant-Accident (LB-LOCA). For this phase, precise requirements step by step were provided to the participants. Four main parts are defined, which are: 1. List and uncertainties of the input uncertain parameters. 2. Uncertainty analysis results. 3. Sensitivity analysis results. 4. Improved methods, assessment of the methods (optional). 5% and 95% percentiles have to be estimated for 6 output parameters, which are of two kinds: 1. Scalar output parameters (First Peak Cladding Temperature (PCT), Second Peak Cladding Temperature, Time of accumulator injection, Time of complete quenching); 2. Time trends output parameters (Maximum cladding temperature, Upper plenum pressure). The main lessons learnt from phase 3 of the BEMUSE programme are the following: - for uncertainty analysis, all the participants use a probabilistic method associated with the use of Wilks' formula, except for UNIPI with its CIAU method (Code with the Capability of Internal Assessment of Uncertainty). Use of both methods has been successfully mastered. - Compared with the experiment, the results of uncertainty analysis are good on the whole. For example, for the cladding temperature-type output parameters (1. PCT, 2. PCT, time of complete quenching, maximum cladding temperature), 8 participants out of 10 find upper and lower bounds which envelop the experimental data. - Sensitivity analysis has been successfully performed by all the participants using the probabilistic method. All the used influence measures include the range of variation of the input parameters. Synthesis tables of the most influential phenomena and parameters have been plotted and participants will be able to use them for the continuation of the BEMUSE programme

  4. Oxidation of Cr(III)-Fe(III) Mixed-phase Hydroxides by Chlorine: Implications on the Control of Hexavalent Chromium in Drinking Water.

    Science.gov (United States)

    Chebeir, Michelle; Liu, Haizhou

    2018-05-17

    The occurrence of chromium (Cr) as an inorganic contaminant in drinking water is widely reported. One source of Cr is its accumulation in iron-containing corrosion scales of drinking water distribution systems as Cr(III)-Fe(III) hydroxide, i.e., FexCr(1-x)(OH)3(s), where x represents the Fe(III) molar content and typically varies between 0.25 and 0.75. This study investigated the kinetics of inadvertent hexavalent chromium Cr(VI) formation via the oxidation of FexCr(1-x)(OH)3(s) by chlorine as a residual disinfectant in drinking water, and examined the impacts of Fe(III) content and drinking water chemical parameters including pH, bromide and bicarbonate on the rate of Cr(VI) formation. Data showed that an increase in Fe(III) molar content resulted in a significant decrease in the stoichiometric Cr(VI) yield and the rate of Cr(VI) formation, mainly due to chlorine decay induced by Fe(III) surface sites. An increase in bicarbonate enhanced the rate of Cr(VI) formation, likely due to the formation of Fe(III)-carbonato surface complexes that slowed down the scavenging reaction with chlorine. The presence of bromide significantly accelerated the oxidation of FexCr(1-x)(OH)3(s) by chlorine, resulting from the catalytic effect of bromide acting as an electron shuttle. A higher solution pH between 6 and 8.5 slowed down the oxidation of Cr(III) by chlorine. These findings suggested that the oxidative conversion of chromium-containing iron corrosion products in drinking water distribution systems can lead to the occurrence of Cr(VI) at the tap, and the abundance of iron, and a careful control of pH, bicarbonate and bromide levels can assist the control of Cr(VI) formation.

  5. Reversed phase chromatographic behaviour of Pu (III), Pu (IV) and Pu (VI) in presence of α-hydroxyisobutyric acid

    International Nuclear Information System (INIS)

    Jaison, P.G.; Telmore, V.M.; Kumar, Pranaw

    2016-01-01

    Understanding the aqueous chemistry of plutonium is important in process conditions as well as in environmental conditions. Since plutonium possesses multiple oxidation states which can coexist in solution, a reliable method for the identification of these oxidation states is essential to understand its physical and chemical processes. The identification of plutonium oxidation states is conventionally determined through a series of liquid-liquid extraction procedures using selective extractants. Spectroscopic and laser based techniques also have been used for the identification of its oxidation state in solutions. Liquid chromatographic behavior of different oxidation states of Pu and other actinide ions is reported to correlate their retention behaviour with stability constants. Objective of the present work is to study the reversed phase chromatography behavior of the three oxidation states of plutonium viz. Pu(III), Pu(IV) and Pu(VI) in presence of á-hydroxyisobutyric acid (HIBA) as an eluent

  6. Should positive phase III clinical trial data be required before proton beam therapy is more widely adopted? No

    International Nuclear Information System (INIS)

    Suit, Herman; Kooy, Hanne; Trofimov, Alexei; Farr, Jonathan; Munzenrider, John; DeLaney, Thomas; Loeffler, Jay; Clasie, Benjamin; Safai, Sairos; Paganetti, Harald

    2008-01-01

    Purpose: Evaluate the rationale for the proposals that prior to a wider use of proton radiation therapy there must be supporting data from phase III clinical trials. That is, would less dose to normal tissues be an advantage to the patient? Methods: Assess the basis for the assertion that proton dose distributions are superior to those of photons for most situations. Consider the requirements for determining the risks of normal tissue injury, acute and remote, in the examination of the data from a trial. Analyze the probable cost differential between high technology photon and proton therapy. Evaluate the rationale for phase III clinical trials of proton vs photon radiation therapy when the only difference in dose delivered is a difference in distribution of low LET radiation. Results: The distributions of biological effective dose by protons are superior to those by X-rays for most clinical situations, viz. for a defined dose and dose distribution to the target by protons there is a lower dose to non-target tissues. This superiority is due to these physical properties of protons: (1) protons have a finite range and that range is exclusively dependent on the initial energy and the density distribution along the beam path; (2) the Bragg peak; (3) the proton energy distribution may be designed to provide a spread out Bragg peak that yields a uniform dose across the target volume and virtually zero dose deep to the target. Importantly, proton and photon treatment plans can employ beams in the same number and directions (coplanar, non-co-planar), utilize intensity modulation and employ 4D image guided techniques. Thus, the only difference between protons and photons is the distribution of biologically effective dose and this difference can be readily evaluated and quantified. Additionally, this dose distribution advantage should increase the tolerance of certain chemotherapeutic agents and thus permit higher drug doses. The cost of service (not developmental) proton

  7. Can harmonized regulation overcome intra-European differences? Insights from a European Phase III stem cell trial.

    Science.gov (United States)

    Hauskeller, Christine

    2017-09-01

    Harmonized regulation of research with human stem cells in Europe has shaped innovation in regenerative medicine. Findings from a Phase III academic clinical trial of an autologous cell procedure illustrate the obstacles that a multinational trial faces. A typology of the obstacles encountered, may help other teams embarking upon trials. The findings throw light on the situation of clinician-scientists in clinical innovation, as the expertise to run scientific trials is very complex. The innovation route of clinical translation takes insufficient account of the interdependencies between multiple social and cultural factors from outside the laboratory and the clinic. For ethical reasons, however, academic and business routes to stem cell treatments ought to be enabled by the regulators. Suggestions arise, how academics can prepare for trials, that academic research needs better institutional support and that new models of medical innovation may need to be developed for regenerative medicine.

  8. Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design.

    Science.gov (United States)

    Pujade-Lauraine, Eric; Fujiwara, Keiichi; Dychter, Samuel S; Devgan, Geeta; Monk, Bradley J

    2018-03-27

    Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in multiple solid tumors. Here, we describe the rationale and design for JAVELIN Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the role of checkpoint inhibition in women with ovarian cancer. This three-arm trial is comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian, fallopian tube or peritoneal cancer. Eligible patients are not preselected based on PD-L1 expression and may have received up to three prior lines of chemotherapy for platinum-sensitive disease, but none for resistant disease. Overall survival and progression-free survival are primary end points, and secondary end points include biomarker evaluations and pharmacokinetics.

  9. OECD/NEA expert group on uncertainty analysis for criticality safety assessment: Results of benchmark on sensitivity calculation (phase III)

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, T.; Laville, C. [Institut de Radioprotection et de Surete Nucleaire IRSN, BP 17, 92262 Fontenay aux Roses (France); Dyrda, J. [Atomic Weapons Establishment AWE, Aldermaston, Reading, RG7 4PR (United Kingdom); Mennerdahl, D. [E Mennerdahl Systems EMS, Starvaegen 12, 18357 Taeby (Sweden); Golovko, Y.; Raskach, K.; Tsiboulia, A. [Inst. for Physics and Power Engineering IPPE, 1, Bondarenko sq., 249033 Obninsk (Russian Federation); Lee, G. S.; Woo, S. W. [Korea Inst. of Nuclear Safety KINS, 62 Gwahak-ro, Yuseong-gu, Daejeon 305-338 (Korea, Republic of); Bidaud, A.; Sabouri, P. [Laboratoire de Physique Subatomique et de Cosmologie LPSC, CNRS-IN2P3/UJF/INPG, Grenoble (France); Patel, A. [U.S. Nuclear Regulatory Commission (NRC), Washington, DC 20555-0001 (United States); Bledsoe, K.; Rearden, B. [Oak Ridge National Laboratory ORNL, M.S. 6170, P.O. Box 2008, Oak Ridge, TN 37831 (United States); Gulliford, J.; Michel-Sendis, F. [OECD/NEA, 12, Bd des Iles, 92130 Issy-les-Moulineaux (France)

    2012-07-01

    The sensitivities of the k{sub eff} eigenvalue to neutron cross sections have become commonly used in similarity studies and as part of the validation algorithm for criticality safety assessments. To test calculations of the sensitivity coefficients, a benchmark study (Phase III) has been established by the OECD-NEA/WPNCS/EG UACSA (Expert Group on Uncertainty Analysis for Criticality Safety Assessment). This paper presents some sensitivity results generated by the benchmark participants using various computational tools based upon different computational methods: SCALE/TSUNAMI-3D and -1D, MONK, APOLLO2-MORET 5, DRAGON-SUSD3D and MMKKENO. The study demonstrates the performance of the tools. It also illustrates how model simplifications impact the sensitivity results and demonstrates the importance of 'implicit' (self-shielding) sensitivities. This work has been a useful step towards verification of the existing and developed sensitivity analysis methods. (authors)

  10. Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting.

    Science.gov (United States)

    Uc, Ergun Y; Doerschug, Kevin C; Magnotta, Vincent; Dawson, Jeffrey D; Thomsen, Teri R; Kline, Joel N; Rizzo, Matthew; Newman, Sara R; Mehta, Sonya; Grabowski, Thomas J; Bruss, Joel; Blanchette, Derek R; Anderson, Steven W; Voss, Michelle W; Kramer, Arthur F; Darling, Warren G

    2014-07-29

    To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p improvements on the flanker task and quality of life (p improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD. This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition. © 2014 American Academy of Neurology.

  11. Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials.

    Science.gov (United States)

    Schroen, Anneke T; Petroni, Gina R; Wang, Hongkun; Gray, Robert; Wang, Xiaofei F; Cronin, Walter; Sargent, Daniel J; Benedetti, Jacqueline; Wickerham, Donald L; Djulbegovic, Benjamin; Slingluff, Craig L

    2010-08-01

    A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (accrual rate) were consistently closed due to insufficient accrual. This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining

  12. A quality assurance audit: phase iii trial of maximal androgen deprivation in prostate cancer (TROG 96.01)

    International Nuclear Information System (INIS)

    Steigler, A.; Kovacev, O.; Denham, J.; Lamb, D.; North, J.

    2000-01-01

    In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998-1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme. Copyright (1999) Blackwell Science Pty Ltd

  13. Phase I/II trial of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Fujii, Masato; Tsukuda, Mamoru; Kubota, Akira; Kida, Akinori; Okami, Kenji

    2003-01-01

    Docetaxel (DOC) is one of the most promising drugs for head and neck cancer (HNSCC). A phase I/II trial of concurrent DOC and radiation for HNSCC was conducted to estimate the recommended dose schedule of DOC, and then to evaluate the therapeutic benefit based on the response and toxicity of the recommended dose schedule. Patients with squamous cell carcinomas of the head and neck were entered. All the patients received radiation with 2.0 Gy single daily fractions up to 60 Gy. DOC was administered weekly for 6 consecutive weeks during radiotherapy. Dose-limiting toxicities, grade 3/4 mucositis and grade 3 pain, manifested in four patients in level 2, and that dose of DOC, 15 mg/m 2 , was considered the maximum tolerated dose (MTD). The recommended dose was decided as 10 mg/m 2 . The phase II study was conducted using DOC at 10 mg/m 2 . Thirty-nine patients with stage II, III or IV were registered, and 35 patients were eligible, 32 patients were evaluable for the response and 34 patients for the toxicity. The overall response rate was 96.9%. The prognoses of the complete response (CR) patients were statistically better than for the partial response (PR) patients. Grade 3 or 4 adverse events consisted of lymphopenia in 64.7%, mucositis in 41.2% and anorexia in 20.6% of the patients. Thirty-two of the 35 eligible patients showed high compliance of over 90%, and their toxicities were manageable. Even low-dose DOC shows a strong effect on HNSCC in combination with radiation, with high survival rates in CR patients. The effect on survival will be assessed by further follow-up. (author)

  14. A quality assurance audit: phase III trial of maximal androgen deprivation in prostate cancer (TROG 96.01).

    Science.gov (United States)

    Steigler, A; Mameghan, H; Lamb, D; Joseph, D; Matthews, J; Franklin, I; Turner, S; Spry, N; Poulsen, M; North, J; Kovacev, O; Denham, J

    2000-02-01

    In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998-1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme.

  15. 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

  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

    2013-02-10

    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.

  17. Clinical efficacy of raltegravir against B and non-B subtype HIV-1 in phase III clinical studies.

    Science.gov (United States)

    Rockstroh, Jürgen K; Teppler, Hedy; Zhao, Jing; Sklar, Peter; Miller, Michael D; Harvey, Charlotte M; Strohmaier, Kim M; Leavitt, Randi Y; Nguyen, Bach-Yen T

    2011-07-17

    We evaluated the long-term efficacy of raltegravir according to HIV-1 subtype (B and non-B) using data from three phase III studies in treatment-experienced (BENCHMRK-1 and 2) and treatment-naive (STARTMRK) HIV-infected patients. HIV-1 subtypes were identified from baseline plasma specimens using genotypic data of the PhenoSense GT test (Monogram Biosciences, South San Francisco, California, USA). Non-B subtypes were combined for the current analyses due to small numbers of each specific subtype. An observed failure approach was used (only discontinuations due to lack of efficacy were treated as failures). Resistance evaluation was performed in patients with documented virologic failure. Seven hundred and forty-three patients received raltegravir and 519 received comparator (efavirenz in STARTMRK; optimized background therapy in BENCHMRK). Non-B subtype virus (A, A/C, A/D, A/G, A1, AE, AG, B/G, BF, C, D, D/F, F, F1, G, and complex) was isolated at baseline in 98 (13%) raltegravir recipients and 62 (12%) comparator recipients. Subtypes AE and C were most common, isolated in 41 and 43 patients, respectively. The proportion of raltegravir recipients achieving HIV RNA less than 50 copies/ml was similar between non-B and B subtypes (STARTMRK: 94.5 vs. 88.7%; BENCHMRK-1 and 2: 66.7 vs. 60.7%); change in CD4 cell count also was similar between non-B and B subtypes (STARTMRK: 243 vs. 221 cells/μl; BENCHMRK-1 and 2: 121 vs. 144 cells/μl). Phenotypic resistance to raltegravir in non-B virus was associated with integrase mutations observed previously in subtype B virus. In phase III studies in treatment-naive and treatment-experienced patients, raltegravir showed comparable and potent clinical efficacy against B and non-B HIV-1 subtypes.

  18. A prospective phase II trial of EGCG in treatment of acute radiation-induced esophagitis for stage III lung cancer

    International Nuclear Information System (INIS)

    Zhao, Hanxi; Xie, Peng; Li, Xiaolin; Zhu, Wanqi; Sun, Xindong; Sun, Xiaorong; Chen, Xiaoting; Xing, Ligang; Yu, Jinming

    2015-01-01

    Background: Acute radiation-induced esophagitis (ARIE) is one of main toxicities complicated by thoracic radiotherapy, influencing patients’ quality of life and radiotherapy proceeding seriously. It is difficult to be cured rapidly so far. Our phase I trial preliminarily showed that EGCG may be a promising strategy in the treatment of ARIE. Materials and methods: We prospectively enrolled patients with stage III lung cancer from the Shandong Tumor Hospital & Institute in China from January 2013 to September 2014. All patients received concurrent or sequential chemo-radiotherapy, or radiotherapy only. EGCG was administrated once ARIE appeared. EGCG was given with the concentration of 440 μmol/L during radiotherapy and additionally two weeks after radiotherapy. RTOG score, dysphagia and pain related to esophagitis were recorded every week. Results: Thirty-seven patients with stage IIIA and IIIB lung cancer were enrolled in this trial. In comparison to the original, the RTOG score in the 1st, 2nd, 3rd, 4th, 5th week after EGCG prescription and the 1st, 2nd week after radiotherapy decreased significantly (P = 0.002, 0.000, 0.000, 0.001, 0.102, 0.000, 0.000, respectively). The pain score of each week was significantly lower than the baseline (P = 0.000, 0.000, 0.000, 0.000, 0.006, 0.000, 0.000, respectively). Conclusion: This trial confirmed that the oral administration of EGCG is an effective and safe method to deal with ARIE. A phase III randomized controlled trial is expected to further corroborate the consequence of EGCG in ARIE treatment

  19. Comprehensive safety assessment of a human inactivated diploid enterovirus 71 vaccine based on a phase III clinical trial.

    Science.gov (United States)

    Zhang, Wei; Kong, Yujia; Jiang, Zhiwei; Li, Chanjuan; Wang, Ling; Xia, Jielai

    2016-04-02

    Human enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). In a previous phase III trial in children, a human diploid cell-based inactivated EV71 vaccine elicited EV71 specific immune responses and protection against EV71 associated HFMD. This study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. This was a randomized, double-blinded, placebo-controlled, phase III clinical trial of a human diploid vaccine carried out in 12,000 children in Guangxi Zhuang Autonomous Region, China (ClinicalTrials.gov: NCT01569581). Solicited events were recorded for 7 days and unsolicited events were reported for 28 days after each injection. Age trend analysis of adverse reaction was conducted in each treatment group. Multiple logistic regression models were built to identify factors influencing the severity of adverse reactions. Fewer solicited adverse reactions were observed in older participants within the first 7 days after vaccination (P < 0.0001), except local pain and pruritus. More severe adverse reactions were observed after the initial injection than after the booster injection. Serious cold or respiratory tract infections (RTI) were observed more often in children aged 6-36 months than in older children. Only the severity of local swelling was associated with body mass index. Children with throat discomfort before injection had a higher risk of serious cold or RTI. These results indicated that the human diploid cell-based vaccine achieved a satisfactory safety profile.

  20. Calibration artefacts in radio interferometry - III. Phase-only calibration and primary beam correction

    Science.gov (United States)

    Grobler, T. L.; Stewart, A. J.; Wijnholds, S. J.; Kenyon, J. S.; Smirnov, O. M.

    2016-09-01

    This is the third installment in a series of papers in which we investigate calibration artefacts. Calibration artefacts (also known as ghosts or spurious sources) are created when we calibrate with an incomplete model. In the first two papers of this series, we developed a mathematical framework which enabled us to study the ghosting mechanism itself. An interesting concomitant of the second paper was that ghosts appear in symmetrical pairs. This could possibly account for spurious symmetrization. Spurious symmetrization refers to the appearance of a spurious source (the antighost) symmetrically opposite an unmodelled source around a modelled source. The analysis in the first two papers indicates that the antighost is usually very faint, in particular, when a large number of antennas are used. This suggests that spurious symmetrization will mainly occur at an almost undetectable flux level. In this paper, we show that phase-only calibration produces an antighost that is N-times (where N denotes the number of antennas in the array) as bright as the one produced by phase and amplitude calibration and that this already bright ghost can be further amplified by the primary beam correction.

  1. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials

    International Nuclear Information System (INIS)

    Chen Zhinan; Mi Li; Xu Jing

    2006-01-01

    Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p 131 I) metuximab injection is safe and active for HCC patients

  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. Phase III clinical evaluation of gadoteridol injection: Experience in pediatric neuro-oncologic MR imaging

    International Nuclear Information System (INIS)

    Debatin, J.F.; Nadel, S.N.; Gray, L.; Trotter, P.; Friedman, H.S.; Hockenberger, B.; Oakes, W.J.

    1992-01-01

    Twenty-two pediatric patients with known CNS neoplasms underwent magnetic resonance (MR) imaging before and after intravenous injection of 0.1 mmol/kg gadoteridol injection as part of a Phase IIIB open label multicenter clinical trial. Intravenous adminstration of this neutral, nonionic contrast agent was found to be safe in children. No clinically relevant changes in vital signs or laboratory values were attributed to the administration of gadoteridol injection. There were no systemic complaints. The imaging characteristics of gadoteridol in pediatric CNS disease appeared similar to those of gadopentetate dimeglumine. The very low toxicity, inherent to this nonionic low osmolal paramagnetic contrast formulation may allow administration of increased doses at increased infusion rates for an increased number of indications with improved sensitivity. (orig.)

  4. Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

    Science.gov (United States)

    Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

    2013-07-15

    Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

  5. Delta phase plutonium and its alloys with III B elements: a microscopic study

    International Nuclear Information System (INIS)

    Bouchet, J.

    2001-01-01

    The plutonium belongs to the actinides where it occupies a crucial place. In the actinide series the competition between the itinerant and local character of the f-electrons is responsible of its unique properties. The series can be divided into two sub-series: the light ( 90 Th- 94 Pu) and the heavy ( 95 Am and beyond) actinides with very different characteristics. The volume behavior of the light actinides is very similar to the one found for the transitions metals with a parabolic decrease of the volume as a function of atomic number. This trend can be explained by the itinerant character of the 5 f electrons which participate to the chemical bonding, and thus the light actinides are considered to form a 5 f transition series. The density functional theory in the local-density approximation (LDA) gives a good description of the ground state of the light actinides in agreement with experiment and a simple Friedel model can explain the parabolic decrease of the volumes. As for heavy actinides, the pattern is reversed: 5 f electrons are localized. This picture places plutonium as the link between the two series, at the transition from delocalized to localized states. The density functional theory within the local density approximation is a very crude approximation for these systems where the on-site interaction between f electrons is strong enough to overcome the kinetic energy. Equilibrium properties for the δ-phase of Pu have been calculated. Taking into account strong electron correlations in the 5 f shell, we show how the equilibrium volume and the bulk modulus are improved in comparison to previous results using the local density approximation (LDA) or the generalized gradient approximation (GGA). In addition, an augmentation of the orbital moment is observed due to the respect of Hund's rules, reducing the total magnetic moment. The stability of the δ-phase is explored and for the first time a positive value for the tetragonal shear constant is found. The

  6. The EORTC module for quality of life in patients with thyroid cancer: phase III.

    Science.gov (United States)

    Singer, Susanne; Jordan, Susan; Locati, Laura D; Pinto, Monica; Tomaszewska, Iwona M; Araújo, Cláudia; Hammerlid, Eva; Vidhubala, E; Husson, Olga; Kiyota, Naomi; Brannan, Christine; Salem, Dina; Gamper, Eva M; Arraras, Juan Ignacio; Ioannidis, Georgios; Andry, Guy; Inhestern, Johanna; Grégoire, Vincent; Licitra, Lisa

    2017-04-01

    The purpose of the study was to pilot-test a questionnaire measuring health-related quality of life (QoL) in thyroid cancer patients to be used with the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire EORTC QLQ-C30. A provisional questionnaire with 47 items was administered to patients treated for thyroid cancer within the last 2 years. Patients were interviewed about time and help needed to complete the questionnaire, and whether they found the items understandable, confusing or annoying. Items were kept in the questionnaire if they fulfilled pre-defined criteria: relevant to the patients, easy to understand, not confusing, few missing values, neither floor nor ceiling effects, and high variance. A total of 182 thyroid cancer patients in 15 countries participated ( n  = 115 with papillary, n  = 31 with follicular, n  = 22 with medullary, n  = 6 with anaplastic, and n  = 8 with other types of thyroid cancer). Sixty-six percent of the patients needed 15 min or less to complete the questionnaire. Of the 47 items, 31 fulfilled the predefined criteria and were kept unchanged, 14 were removed, and 2 were changed. Shoulder dysfunction was mentioned by 5 patients as missing and an item covering this issue was added. To conclude, the EORTC quality of life module for thyroid cancer (EORTC QLQ-THY34) is ready for the final validation phase IV. © 2017 Society for Endocrinology.

  7. Post-treatment resistance analysis of hepatitis C virus from phase II and III clinical trials of ledipasvir/sofosbuvir.

    Science.gov (United States)

    Wyles, David; Dvory-Sobol, Hadas; Svarovskaia, Evguenia S; Doehle, Brian P; Martin, Ross; Afdhal, Nezam H; Kowdley, Kris V; Lawitz, Eric; Brainard, Diana M; Miller, Michael D; Mo, Hongmei; Gane, Edward J

    2017-04-01

    Ledipasvir/sofosbuvir combination treatment in phase III clinical trials resulted in sustained viral suppression in 94-99% of patients. This study characterized drug resistance in treatment failures, which may help to inform retreatment options. We performed NS5A and NS5B deep sequencing of hepatitis C virus (HCV) from patients infected with genotype (GT) 1 who participated in ledipasvir/sofosbuvir phase II and III clinical trials. Fifty-one of 2144 (2.4%) (42 GT1a and 9 GT1b) treated patients met the criteria for resistance analysis due to virologic failure following the end of treatment. The majority of patients with virologic failure (38 of 51; 74.5%) had detectable ledipasvir-specific resistance-associated substitutions (RASs) at the time of virologic failure (1% deep sequencing cut-off). The percent of patients with NS5A RASs at virologic failure were 37.5%, 66.7%, 94.7% and 100% in patients treated for 6, 8, 12 and 24weeks, respectively. The common substitutions detected at failure were Q30R/H, and/or Y93H/N in GT1a and Y93H in GT1b. At failure, 35.3% (18/51) of virologic failure patients' viruses had two or more NS5A RASs and the majority of patients harbored NS5A RASs conferring a 100-1000-fold (n=10) or >1000-fold (n=23) reduced susceptibility to ledipasvir. One patient in a phase II study with a known ledipasvir RAS at baseline (L31M) developed the S282T sofosbuvir (NS5B) RAS at failure. In GT1 HCV-infected patients treated with ledipasvir/sofosbuvir±ribavirin, virologic failure was rare. Ledipasvir resistance in NS5A was selected or enhanced in most patients with virologic failure, one of whom also developed resistance to sofosbuvir. Clinical studies have shown that combination treatment with ledipasvir/sofosbuvir efficiently cures most patients with genotype 1 hepatitis C infection. For the few patients failing treatment, we show that resistance to ledipasvir was observed in most patients, whereas resistance to sofosbuvir was less common. This has

  8. Phase-coherent transport and spin-orbit-coupling in III/V-semiconductor nanowires

    International Nuclear Information System (INIS)

    Estevez Hernandez, Sergio

    2009-01-01

    Semiconductor nanowires fabricated by a bottom-up approach are not only interesting for the realization of future nanoscaled devices but also appear to be very attractive model systems to tackle fundamental questions concerning the transport in strongly confined systems. In order to avoid the problem connected with carrier depletion, narrowband gap semiconductors, i.e., InAs or InN, or core-shell Nanowires, i.e., GaAs/AlGaAs, are preferred. The underlying reason is that in InAs or InN the Fermi-level pinning in the conduction band results in a carrier accumulation at the surface. In fact, the tubular topology of the surface electron gas opens up the possibility to observe unconventional quantum transport phenomena. When the phase-coherence length in the nanowire is comparable to its dimensions the conductance fluctuates if a magnetic field is applied or if the electron concentration is changed by means of a gate electrode. These so-called universal conductance fluctuations being in the order of e 2 /h originate from the fact that in small disordered samples, electron interference effects are not averaged out. In this work are analyzed universal conductance fluctuations to study the quantum transport properties in InN, InAs and GaAs/AlGaAs nanowires. With the use of a magnetic field and a back-gate electrode the universal conductance fluctuations and localizations effects were analyzed. Since InN and InAs are narrow band gap semiconductors, one naturally expects spin-orbit coupling effects. Because this phenomena is of importance for spin electronic applications. However, owing to the cylindrical symmetry of the InN and InAs nanowires, the latter effect was observable and actually be used to determine the strength of spin-orbit coupling. In order to clearly separate the weak antilocalization effect from the conductance fluctuations, the averaging of the magnetoconductance at different gate voltages was essential. The low-temperature quantum transport properties of

  9. NOVEL CONCEPTS RESEARCH IN GEOLOGIC STORAGE OF CO2 PHASE III

    Energy Technology Data Exchange (ETDEWEB)

    Neeraj Gupta

    2006-01-23

    As part of the Department of Energy's (DOE) initiative on developing new technologies for storage of carbon dioxide in geologic reservoirs, Battelle has been investigating the feasibility of CO{sub 2} sequestration in the deep saline reservoirs in the Ohio River Valley region. In addition to the DOE, the project is being sponsored by American Electric Power (AEP), BP, The Ohio Coal Development Office (OCDO) of the Ohio Air Quality Development Authority, Schlumberger, and Battelle. The main objective of the project is to demonstrate that CO{sub 2} sequestration in deep formations is feasible from engineering and economic perspectives, as well as being an inherently safe practice and one that will be acceptable to the public. In addition, the project is designed to evaluate the geology of deep formations in the Ohio River Valley region in general and in the vicinity of AEP's Mountaineer Power Plant in particular, in order to determine their potential use for conducting a long-term test of CO{sub 2} disposal in deep saline formations. The current technical progress report summarizes activities completed for the October through December 2005 period of the project. As discussed in the following report, the main field activity was reservoir testing in the Copper Ridge ''B-zone'' in the AEP No.1 well. In addition reservoir simulations were completed to assess feasibility of CO{sub 2} injection for the Mountaineer site. These reservoir testing and computer simulation results suggest that injection potential may be substantially more than anticipated for the Mountaineer site. Work also continued on development of injection well design options, engineering assessment of CO{sub 2} capture systems, permitting, and assessment of monitoring technologies as they apply to the project site. Overall, the current design feasibility phase project is proceeding according to plans.

  10. Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase I/II clinical trial.

    Science.gov (United States)

    Wong, Wai T; Dresner, Samuel; Forooghian, Farzin; Glaser, Tanya; Doss, Lauren; Zhou, Mei; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y

    2013-04-26

    To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA). The study was a single-center, open-label phase II trial, enrolling 11 participants with bilateral GA; eight participants completed 24 months of follow-up. Sirolimus (440 μg) was administered every 3 months as a subconjunctival injection in only one randomly assigned eye in each participant for 24 months. Fellow eyes served as untreated controls. The primary efficacy outcome measure was the change in the total GA area at 24 months. Secondary outcomes included changes in visual acuity, macular sensitivity, central retinal thickness, and total drusen area. The study drug was well tolerated with few symptoms and related adverse events. Study treatment in study eyes was not associated with structural or functional benefits relative to the control fellow eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0 letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03). Substantial differences in mean changes in drusen area, central retinal thickness, and macular sensitivity were not detected for all analysis time points up to 24 months. Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).

  11. Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab.

    Science.gov (United States)

    Weber, Jeffrey; Gibney, Geoffrey; Kudchadkar, Ragini; Yu, Bin; Cheng, Pingyan; Martinez, Alberto J; Kroeger, Jodie; Richards, Allison; McCormick, Lori; Moberg, Valerie; Cronin, Heather; Zhao, Xiuhua; Schell, Michael; Chen, Yian Ann

    2016-04-01

    The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3-4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%-41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naïve and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3-4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%-82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3-4 immune-related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab. ©2016 American Association for Cancer Research.

  12. Phase I study of cisplatin, vinorelbine, and concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Sekine, Ikuo

    2004-01-01

    To determine the recommended phase II dose of vinorelbine in combination with cisplatin and thoracic radiotherapy (TRT) in patients with unresectable stage III non-small cell lung cancer (NSCLC), 18 patients received cisplatin (80 mg/m 2 ) on day 1 and vinorelbine (20 mg/m 2 in level 1, and 25 mg/m 2 in level 2) on days 1 and 8 every 4 weeks for 4 cycles. TRT consisted of a single dose of 2 Gy once daily for 3 weeks followed by a rest of 4 days, and then the same TRT for 3 weeks to a total dose of 60 Gy. Fifteen (83%) patients received 60 Gy of TRT and 14 (78%) patients received 4 cycles of chemotherapy. Ten (77%) of 13 patients at level 1 and all 5 patients at level 2 developed grade 3-4 neutropenia. Four (31%) patients at level 1 and 3 (60%) patients at level 2 developed grade 3-4 infection. None developed ≥grade 3 esophagitis or lung toxicity. Dose-limiting toxicity was noted in 33% of the patients in level 1 and in 60% of the patients in level 2. The overall response rate (95% confidence interval) was 83% (59-96%) with 15 partial responses. The median survival time was 30.4 months, and the 1-year, 2-year, and 3-year survival rates were 72%, 61%, and 50%, respectively. In conclusion, the recommended dose is the level 1 dose, and this regimen is feasible and promising in patients with stage III NSCLC. (author)

  13. A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients.

    Science.gov (United States)

    Floege, Jürgen; Covic, Adrian C; Ketteler, Markus; Rastogi, Anjay; Chong, Edward M F; Gaillard, Sylvain; Lisk, Laura J; Sprague, Stuart M

    2014-09-01

    Efficacy of PA21 (sucroferric oxyhydroxide), a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder, was compared with that of sevelamer carbonate in an open-label, randomized, active-controlled phase III study. Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0-3.0 g per day and 348 received sevelamer 4.8-14.4 g per day for an 8-week dose titration, followed by 4 weeks without dose change, and then 12 weeks maintenance. Serum phosphorus reductions at week 12 were -0.71 mmol/l (PA21) and -0.79 mmol/l (sevelamer), demonstrating non-inferiority of, on average, three tablets of PA21 vs. eight of sevelamer. Efficacy was maintained to week 24. Non-adherence was 15.1% (PA21) vs. 21.3% (sevelamer). The percentage of patients that reported at least one treatment-emergent adverse event was 83.2% with PA21 and 76.1% with sevelamer. A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 (15.7%) vs. sevelamer (6.6%). Mild, transient diarrhea, discolored feces, and hyperphosphatemia were more frequent with PA21; nausea and constipation were more frequent with sevelamer. After 24 weeks, 99 hemodialysis patients on PA21 were re-randomized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose (250 mg per day (ineffective control)) in 49 patients. The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control. Thus, PA21 was effective in lowering serum phosphorus in dialysis patients, with similar efficacy to sevelamer carbonate, a lower pill burden, and better adherence.

  14. Motivations to participate in a Phase I/II HIV vaccine trial: A descriptive study from Dar es Salaam, Tanzania

    Directory of Open Access Journals (Sweden)

    E. A. M. Tarimo

    2016-02-01

    Full Text Available Abstract Background The search for an efficacious HIV vaccine is a global priority. To date only one HIV vaccine trial (RV144 has shown modest efficacy in a phase III trial. With existing different HIV-1 subtypes and frequent mutations, multiple trials are needed from different geographical sites particularly in sub-Saharan Africa where most HIV infections occur. Thus, motivations to participate in HIV vaccine trials among Tanzanians need to be assessed. This paper describes the motives of Police Officers who showed great interest to volunteer in HIVIS-03 in Dar es Salaam, Tanzania. Methods A descriptive cross-sectional study was conducted among Police Officers who showed interest to participate in the HIVIS-03, a phase I/II HIV vaccine trial in Dar es Salaam. Prior to detailed training sessions about HIV vaccine trials, the potential participants narrated their individual motives to participate in the trial on a piece of paper. Descriptive analysis using content approach and frequency distributions were performed. Results Of the 265 respondents, 242 (91.3 % provided their socio-demographic characteristics as well as reasons that would make them take part in the proposed trial. Majority, (39.7 %, cited altruism as the main motive. Women were more likely to volunteer due to altruism compared to men (P < 0.01. Researchers’ explanations about HIV/AIDS vaccine studies motivated 15.3 %. More men (19.6 % than women (1.7 % were motivated to volunteer due to researchers’ explanations (P < 0.001. Also, compared to other groups, those unmarried and educated up to secondary level of education were motivated to volunteer due to researchers’ explanation (P < 0.05. Other reasons were: desire to become a role model (18.6 %; to get knowledge for educating others (14.0 %; to cooperate with researchers in developing an HIV vaccine (9.5 %; to get protection against HIV infection (7.0 %, and severity of the disease within families (6.2

  15. Successful completion of the Qinshan phase III nuclear power plant-a successful model for Chinese-Canadian cooperation

    International Nuclear Information System (INIS)

    Peng Xiaoxing

    2004-01-01

    This report documents Qinshan CANDU project construction and commissioning experience as well as management strategies and approaches that contributed to the successful completion of the project. The Qinshan phase III (CANDU) nuclear power plant was built in record times: Unit 1 achieved commercial operation on December 31, 2002 and Unit 2 on July 24, 2003, 43 days and 112 days ahead of schedule respectively. The reference plant design is the Wolsong 3 and 4 CANDU-6 units in the Republic of Korea. Improvements in design and construction methods allowed Unit 1 to be constructed in 51.5 Months from First Concrete to Criticality-a record in China for nuclear power plants. The key factors are project management and project management tools, quality assurance, construction methods (including open top construction, heavy lifts and modularization), electronic documentation with configuration control that provides up-to-date on-line information, CADDS design linked with material management, specialized material control including bar coding, and planning. The introduction of new design and construction techniques was achieved by combining conventional AECL practices with working experiences in China. The most advanced tools and techniques for achieving optimum construction quality, schedule and cost were used. Successful application of advanced project management methods and tools will benefit TQNPC in operation of the station, and the Chinese contractors in advancing their capabilities in future nuclear projects in China and enhancing their opportunities internationally. TQNPC's participation in Quality surveillance (QS) activities of nuclear steam plant (NSP) and Balance of Plant (BOP) offshore equipment benefited TQNPC in acquiring knowledge of specific equipment manufacturing processes, which can be applied to similar activities in China. China has established the capability of manufacturing CANDU fuel and becoming self-reliant in fuel supply. Excellent co-operation and

  16. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

    Science.gov (United States)

    Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

    2010-07-01

    Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

  17. Comparison of DNA double-strand break rejoining as measured by pulsed field gel electrophoresis, neutral sucrose gradient centrifugation and non-unwinding filter elution in irradiated plateau-phase CHO cells

    International Nuclear Information System (INIS)

    Iliakis, G.; Metzger, L.; Pantelias, G.

    1991-01-01

    The initial (up to 30 min) rate of DNA double-strand break (dsb) rejoining was measured in irradiated plateau-phase CHO cells, in a set of parallel experiments using the same cell suspension, by means of non-unwinding filter elution, neutral sucrose gradient centrifugation, and two pulsed-field gel electrophoresis assays: asymmetric field inversion gel electrophoresis (AFIGE) and clamped homogeneous electric field (CHEF) gel electrophoresis. The rate of DNA dsb rejoining was compared to the rate of rejoining of chromatin breaks measured, also in the same cell population, using the technique of premature chromosome condensation (PCC). Two radiation exposures, 25 Gy and/or 50 Gy, were used and applied to the individual parts of the experiments according to the sensitivity of the assay under investigation. The results suggest all major techniques currently used for assaying rejoining of DNA dsb give similar results, and indicate that more information is required before a direct correlation between rejoining of DNA dsb and rejoining of chromatin breaks can be established. (author)

  18. Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Apornwirat, Wichit; Shaharyar, Ahmed

    2009-01-01

    PURPOSE: The purpose of this phase III trial was to evaluate the efficacy and safety of regimens containing casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting during the first cycle in patients receiving moderately emetogenic chemo...

  19. 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....

  20. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Tveit, Kjell Magne; Guren, Tormod; Glimelius, Bengt

    2012-01-01

    The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation...

  1. Bortezomib before and after high-dose therapy in myeloma : Long-term results from the phase III HOVON-65/GMMGHD-4 trial

    NARCIS (Netherlands)

    Goldschmidt, H.; Lokhorst, H. M.; Mai, E. K.; van der Holt, B.; Blau, I. W.; Zweegman, S.; Weisel, K. C.; Vellenga, E.; Pfreundschuh, M.; Kersten, M. J.; Scheid, C.; Croockewit, S.; Raymakers, R.; Hose, D.; Potamianou, A.; Jauch, A.; Hillengass, J.; Stevens-Kroef, M.; Raab, M. S.; Broijl, A.; Lindemann, H. W.; Bos, G. M. J.; Brossart, P.; Kooy, M. van Marwijk; Ypma, P.; Duehrsen, U.; Schaafsma, R. M.; Bertsch, U.; Hielscher, T.; Jarari, Le; Salwender, H. J.; Sonneveld, P.

    The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical

  2. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial

    NARCIS (Netherlands)

    Goldschmidt, H.; Lokhorst, H. M.; Mai, E. K.; van der Holt, B.; Blau, I. W.; Zweegman, S.; Weisel, K. C.; Vellenga, E.; Pfreundschuh, M.; Kersten, M. J.; Scheid, C.; Croockewit, S.; Raymakers, R.; Hose, D.; Potamianou, A.; Jauch, A.; Hillengass, J.; Stevens-Kroef, M.; Raab, M. S.; Broijl, A.; Lindemann, H. W.; Bos, G. M. J.; Brossart, P.; van Marwijk Kooy, M.; Ypma, P.; Duehrsen, U.; Schaafsma, R. M.; Bertsch, U.; Hielscher, T.; Jarari, Le; Salwender, H. J.; Sonneveld, P.

    2018-01-01

    The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical

  3. Effects of recombinant human granulocyte colony-stimulating factor on leucopenia in zidovudine-treated patients with AIDS and AIDS related complex, a phase I/II study

    NARCIS (Netherlands)

    van der Wouw, P. A.; van Leeuwen, R.; van Oers, R. H.; Lange, J. M.; Danner, S. A.

    1991-01-01

    Twelve male patients, eight with the acquired immunodeficiency syndrome (AIDS) and four with AIDS related complex (ARC), who had zidovudine associated neutropenia (less than 1 x 10(9) neutrophils/l) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) in a phase I/II

  4. Rituximab Maintenance Treatment of Relapsed/Resistant Follicular Non-Hodgkin's Lymphoma: Long-Term Outcome of the EORTC 20981 Phase III Randomized Intergroup Study

    NARCIS (Netherlands)

    van Oers, Marinus H. J.; van Glabbeke, Martine; Giurgea, Livia; Klasa, Richard; Marcus, Robert E.; Wolf, Max; Kimby, Eva; van 't Veer, Mars; Vranovsky, Andrej; Holte, Harald; Hagenbeek, Anton

    2010-01-01

    Purpose In 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the

  5. Recruiting long-term survivors of European Organisation for Research and Treatment of Cancer phase III clinical trials into quality of life studies : Challenges and opportunities

    NARCIS (Netherlands)

    van Leeuwen, M.L.; Efficace, F.; Fosså, S.D.; Bolla, M.; de Giorgi, U.; De Wit, R.; Holzner, B.; van de Poll-Franse, L.; White, J.; Collette, L.; Osanto, S.; Aaronson, N.K.; European Organisation for Research and Treatment of Cancer Quality of Life Group; Genito-Urinary Cancers Group, The

    2014-01-01

    Objectives In this pilot study we evaluated the feasibility of and methods for assessing the quality of life of long term survivors of European Organisation for Research and Treatment of Cancer (EORTC) phase III clinical trials. Here we report the results pertaining to the feasibility of conducting

  6. Recruiting long-term survivors of European Organisation for Research and Treatment of Cancer phase III clinical trials into quality of life studies: Challenges and opportunities

    NARCIS (Netherlands)

    van Leeuwen, M.; Efficace, F.; Fosså, S.D.; Bolla, M.; De Giorgi, U.; de Wit, R; Holzner, B.; van de Poll-Franse, L.V.; van Poppel, H.; White, J.; Collette, L.; Osanto, S.; Aaronson, N.K.

    2014-01-01

    Objectives: In this pilot study we evaluated the feasibility of and methods for assessing the quality of life of long term survivors of European Organisation for Research and Treatment of Cancer (EORTC) phase III clinical trials. Here we report the results pertaining to the feasibility of conducting

  7. 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

  8. Current Practices in the Treatment of Alzheimer Disease: Where is the Evidence After the Phase III Trials?

    Science.gov (United States)

    Ehret, Megan J; Chamberlin, Kevin W

    2015-08-01

    The purpose of this systematic review was to review the current place in therapy of the 4 medications, donepezil, rivastigmine, galantamine, and memantine, approved for the treatment of Alzheimer disease (AD) since the publication of Phase III trials. A systematic literature search of MEDLINE and EMBASE was conducted for articles published in the past 10 years. The search was performed using the following Medical Subject Headings and text key words: Alzheimer's disease, treatment, donepezil, galantamine, rivastigmine, memantine, dementia of the Alzheimer's type, and dementia. Studies that evaluated new doses, indications, and dose formulations remain a large part of the current literature. Donepezil gained approval for the treatment of severe AD and became available in a 23-mg/d dose formulation. Rivastigmine became available in a patch formulation. Memantine became available as an extended-release capsule. Use of a combination product formulation was recently approved, memantine extended release/donepezil. Controversy among clinicians remains regarding when to initiate therapy, appropriate duration of therapy, and how and when to discontinue the treatment of AD. Only drugs that affect cholinergic function have shown consistent, but modest, clinical effects, even in late-phase trials. There is a need for a better appreciation of the various risk factors and drug targets for the treatment of AD. The wide range of targets makes it unlikely that affecting only 1 of those targets (eg, cholinergic function or N-methyl-d-aspartate) will lead to a more than minimally effective treatment option, regardless of when a treatment is started and discontinued. There is substantial opportunity for the continued growth and development of drugs and clinical trial expansion for the treatment of AD. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  9. Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.

    Science.gov (United States)

    Petrou, Philip A; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A; Ferris, Frederick L; Chew, Emily Y; Wong, Wai T

    2014-12-18

    To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  10. Resource Use and Costs of Dengue: Analysis of Data from Phase III Efficacy Studies of a Tetravalent Dengue Vaccine.

    Science.gov (United States)

    El Fezzazi, Hanna; Branchu, Marie; Carrasquilla, Gabriel; Pitisuttithum, Punnee; Perroud, Ana Paula; Frago, Carina; Coudeville, Laurent

    2017-12-01

    A tetravalent dengue vaccine (CYD-TDV) has recently been approved in 12 countries in southeast Asia and Latin America for individuals aged 9-45 years or 9-60 years (age indication approvals vary by country) living in endemic areas. Data on utilization of medical and nonmedical resources as well as time lost from school and work were collected during the active phase of two phase III efficacy studies performed in 10 countries in the Asia-Pacific region and Latin America (NCT01373281; NCT01374516). We compared dengue-related resource utilization and costs among vaccinated and nonvaccinated participants. Country-specific unit costs were derived from available literature. There were 901 virologically confirmed dengue episodes among participants aged ≥ 9 years ( N = 25,826): corresponding to 373 episodes in the CYD-TDV group ( N = 17,230) and 528 episodes in the control group ( N = 8,596). Fewer episodes in the CYD-TDV group resulted in hospitalization than in the control group (7.0% versus 13.3%; P = 0.002), but both had a similar average length of stay of 4 days. Overall, a two-thirds reduction in resource consumption and missed school/work days was observed in the CYD-TDV group relative to the control group. The estimated direct and indirect cost (2014 I$) associated with dengue episodes per participant in the CYD-TDV group was 73% lower than in the control group (I$6.72 versus I$25.08); representing a saving of I$I8.36 (95% confidence interval [CI]:17.05-19.78) per participant with vaccination. This is the first study providing information on dengue costs among vaccinated individuals and direct confirmation that vaccination has the potential to reduce dengue illness costs.

  11. 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).

  12. Column Chromatography Of Co(II), Zn(II) And Eu(III) Using Pistachio Shell And Different Mobile Phases

    International Nuclear Information System (INIS)

    Abdel-Fattah, A.A.

    2009-01-01

    Pistachio shell particles (0.5-1 mm) have been applied as the stationary phase for studying the column chromatography of Co(II), Zn(II) and Eu(III) at room temperature; 26 + - 1 oC. This solid sorbent has been characterized by thermogravimetric analysis, infra-red spectroscopy and X-ray diffraction. Its surface area and percent of swelling have been also determined. Different eluting agents have been used for eluting the sorbed elements. The elution curves have been done from which the distribution coefficients (K d ), number of theoretical plates (N) and heights equivalent to theoretical plates (H) have been determined. Column performance studies have been conducted for a representative system under certain experimented conditions and Van Deemter equation has been applied. Thermodynamic studies have been applied and thermodynamic functions ( δG 0 ,δH 0 andδ S 0 ) have been calculated for this representative system by determining K d at three different room temperatures (18, 26 and 37 + - 1o C).

  13. Randomized phase III trial of regorafenib in metastatic colorectal cancer: analysis of the CORRECT Japanese and non-Japanese subpopulations.

    Science.gov (United States)

    Yoshino, Takayuki; Komatsu, Yoshito; Yamada, Yasuhide; Yamazaki, Kentaro; Tsuji, Akihito; Ura, Takashi; Grothey, Axel; Van Cutsem, Eric; Wagner, Andrea; Cihon, Frank; Hamada, Yoko; Ohtsu, Atsushi

    2015-06-01

    In the international, phase III, randomized, double-blind CORRECT trial, regorafenib significantly prolonged overall survival (OS) versus placebo in patients with metastatic colorectal cancer (mCRC) that had progressed on all standard therapies. This post hoc analysis evaluated the efficacy and safety of regorafenib in Japanese and non-Japanese subpopulations in the CORRECT trial. Patients were randomized 2 : 1 to regorafenib 160 mg once daily or placebo for weeks 1-3 of each 4-week cycle. The primary endpoint was OS. Outcomes were assessed using descriptive statistics. One hundred Japanese and 660 non-Japanese patients were randomized to regorafenib (n = 67 and n = 438) or placebo (n = 33 and n = 222). Regorafenib had a consistent OS benefit in the Japanese and non-Japanese subpopulations, with hazard ratios of 0.81 (95 % confidence interval [CI] 0.43-1.51) and 0.77 (95 % CI 0.62-0.94), respectively. Regorafenib-associated hand-foot skin reaction, hypertension, proteinuria, thrombocytopenia, and lipase elevations occurred more frequently in the Japanese subpopulation than in the non-Japanese subpopulation, but were generally manageable. Regorafenib appears to have comparable efficacy in Japanese and non-Japanese subpopulations, with a manageable adverse-event profile, suggesting that this agent could potentially become a standard of care in patients with mCRC.

  14. Column Chromatography Of Co(II), Zn(II) And Eu(III) Using Pistachio Shell And Different Mobile Phases

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Fattah, A A [Nuclear Chemistry Department, Radioisotopes Production Division, Hot Laboratories Centre, Atomic Energy Authority, Cairo (Egypt)

    2009-07-01

    Pistachio shell particles (0.5-1 mm) have been applied as the stationary phase for studying the column chromatography of Co(II), Zn(II) and Eu(III) at room temperature; 26{sup +}-{sup 1}oC. This solid sorbent has been characterized by thermogravimetric analysis, infra-red spectroscopy and X-ray diffraction. Its surface area and percent of swelling have been also determined. Different eluting agents have been used for eluting the sorbed elements. The elution curves have been done from which the distribution coefficients (K{sub d}), number of theoretical plates (N) and heights equivalent to theoretical plates (H) have been determined. Column performance studies have been conducted for a representative system under certain experimented conditions and Van Deemter equation has been applied. Thermodynamic studies have been applied and thermodynamic functions ( {delta}G{sup 0} ,{delta}H{sup 0} and{delta} S{sup 0}) have been calculated for this representative system by determining K{sub d} at three different room temperatures (18, 26 and 37{sup +}-{sup 1o}C)

  15. Iodixanol in cerebral computed tomography: a randomized, double-blind, phase-III, parallel study with iodixanol and iohexol

    International Nuclear Information System (INIS)

    Doerfler, A.; Wanke, I.; Forsting, M.; Fiebach, J.; Sartor, K.; Henseke, P.

    1999-01-01

    Iodixanol is a new nonionic dimer, isotonic with blood at all clinically relevant concentrations. Iodixanol (270 mg I/ml) was compared in a double-blind, randomized, parallel-group, phase-III study to the monomeric nonionic iohexol (300 mg I/ml) for evaluation of safety, tolerability and radiographic efficacy during cerebral CT. One hundred adult patients scheduled to undergo contrast-enhanced cerebral CT were randomly allocated to receive either iodixanol or iohexol. All completed the trial. Safety was evaluated by recording discomfort and other adverse events, tolerance by assessing intensity and incidence of discomfort. Radiographic efficacy was assessed from the diagnostic information and the radiographic density. No serious adverse events occurred. One patient (2 %) in the iodixanol group and one patient (2 %) in the iohexol group experienced a transient reddening at the neck and lower neck-line, respectively. Both contrast agents were well tolerated. One patient (2 %) in the iodixanol group and two patients (4 %) in the iohexol group experienced a sensation of warmth (discomfort) in connection with the injection. No difference between the two contrast media were noted radiographically. This comparison between iodixanol and iohexol showed both contrast media to be safe, well-tolerated and efficacious for use in cerebral CT. (orig.)

  16. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial.

    Science.gov (United States)

    Posner, M R; Lorch, J H; Goloubeva, O; Tan, M; Schumaker, L M; Sarlis, N J; Haddad, R I; Cullen, K J

    2011-05-01

    The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.

  17. "cART intensification by the HIV-1 Tat B clade vaccine: progress to phase III efficacy studies".

    Science.gov (United States)

    Cafaro, Aurelio; Sgadari, Cecilia; Picconi, Orietta; Tripiciano, Antonella; Moretti, Sonia; Francavilla, Vittorio; Pavone Cossut, Maria Rosaria; Buttò, Stefano; Cozzone, Giovanni; Ensoli, Fabrizio; Monini, Paolo; Ensoli, Barbara

    2018-02-01

    In spite of its success at suppressing HIV replication, combination antiretroviral therapy (cART) only partially reduces immune dysregulation and loss of immune functions. These cART-unmet needs appear to be due to persistent virus replication and cell-to-cell transmission in reservoirs, and are causes of increased patients' morbidity and mortality. Up to now, therapeutic interventions aimed at cART-intensification by attacking the virus reservoir have failed. Areas covered: We briefly review the rationale and clinical development of Tat therapeutic vaccine in cART-treated subjects in Italy and South Africa (SA). Vaccination with clade-B Tat induced cross-clade neutralizing antibodies, immune restoration, including CD4 + T cell increase particularly in low immunological responders, and reduction of proviral DNA. Phase III efficacy trials in SA are planned both in adult and pediatric populations. Expert commentary: We propose the Tat therapeutic vaccine as a pathogenesis-driven intervention that effectively intensifies cART and may lead to a functional cure and provide new perspectives for prevention and virus eradication strategies.

  18. Disclosure of funding sources and conflicts of interest in phase III surgical trials: survey of ten general surgery journals.

    Science.gov (United States)

    Bridoux, Valérie; Moutel, Grégoire; Schwarz, Lilian; Michot, Francis; Herve, Christian; Tuech, Jean-Jacques

    2014-10-01

    Discussions regarding disclosure of funding sources and conflicts of interest (COI) in published peer-reviewed journal articles are becoming increasingly more common and intense. The aim of the present study was to examine whether randomized controlled trials (RCTs) published in leading surgery journals report funding sources and COI. All articles reporting randomized controlled phase III trials published January 2005 through December 2010 were chosen for review from ten international journals. We evaluated the number of disclosed funding sources and COI, and the factors associated with such disclosures. From a review of 657 RCT from the ten journals, we discovered that presence or absence of a funding source and COI was disclosed by 47 % (309) and 25.1 % (165), respectively. Most articles in "International Committee of Medical Journal Editors (ICMJE)-affiliated journals" did not disclose COI. Disclosure of funding was associated with a journal impact factor >3 (51.7 vs 41.6 %; p funding sources (i.e., whether or not there was a funding source), and almost three quarters did not disclose whether COI existed. Our findings suggest the need to adopt best current practices regarding disclosure of competing interests to fulfill responsibilities to readers and, ultimately, to patients.

  19. Nature of the Blue-Phase-III endash isotropic critical point: An analogy with the liquid-gas transition

    International Nuclear Information System (INIS)

    Anisimov, M.A.; Agayan, V.A.; Collings, P.J.

    1998-01-01

    The analogy with the liquid-gas critical point is analyzed to clarify the nature of the pretransitional behavior of physical properties in the vicinity of the Blue-Phase-III endash isotropic transition in chiral liquid crystalline systems. The analogy is unusual: temperature serves as the ordering field and entropy plays the role of the order parameter. Both mean field and parametric equations of state are formulated in terms of scaling fields. The scaling fields are linear combinations of the physical fields, which are temperature and chirality. It is shown that mixing of the physical field variables naturally leads to a strong asymmetry with respect to the transition temperature in the behavior of the physical properties that cannot be described by simple power laws. While the mean field theory gives a good description of the experimental data, the scaling theory, if one incorporates mixing of the field variables, gives even better agreement with the experimental data, placing this transition in the same universality class as the three-dimensional Ising model. copyright 1998 The American Physical Society

  20. Acoustic Detection of Faults and Degradation in a High-Bypass Turbofan Engine during VIPR Phase III Testing

    Science.gov (United States)

    Boyle, Devin K.

    2017-01-01

    The Vehicle Integrated Propulsion Research (VIPR) Phase III project was executed at Edwards Air Force Base, California, by the National Aeronautics and Space Administration and several industry, academic, and government partners in the summer of 2015. One of the research objectives was to use external radial acoustic microphone arrays to detect changes in the noise characteristics produced by the research engine during volcanic ash ingestion and seeded fault insertion scenarios involving bleed air valves. Preliminary results indicate the successful acoustic detection of suspected degradation as a result of cumulative exposure to volcanic ash. This detection is shown through progressive changes, particularly in the high-frequency content, as a function of exposure to greater cumulative quantities of ash. Additionally, detection of the simulated failure of the 14th stage stability bleed valve and, to a lesser extent, the station 2.5 stability bleed valve, to their fully-open fail-safe positions was achieved by means of spectral comparisons between nominal (normal valve operation) and seeded fault scenarios.

  1. Myocardial perfusion imaging with Technetium-99m Sestamibi and Thallium-201. Results of the phase III clinical trial

    International Nuclear Information System (INIS)

    Giering, L.; Haber, S.; Joseph, J.L.; Neacy, W.

    1998-01-01

    Full text: Technetium-99m-Sestamibi (MIBI) has been compared to 201 TI and coronary angiography in a large Phase III clinical trial to assess diagnostic accuracy. Exercise and rest planar (P) and SPECT (S) MIBI, and exercise and redistribution thallium-201 studies were performed in 150 healthy volunteers and 396 patients (379 males; mean age 51.3 years). Prior myocardial infarction was present in 50% of the patients. Sensitivity and specificity for angiographically defined cardiovascular diseases - CAD (>70% stenosis) for planar imaging was 90.3% and 81.3% for MIBI and 91.6% and 50.0% for 201 TI. Agreement was 88.7% MIBI and 84.0% for 201 TI. For SPECT imaging, sensitivity and specificity were 95.1% and 46.0% for MIBI and 92.3% and 39.7% for 201 TI. Agreement was 80.0% for MIBI and 76.1% for 201 TI. Tomographic normality rates were 91.4% and 92.9% for MIBI and 201 TI. Agreement for characterisation of defect type by MIBI and 201 TI SPECT was 82.5%. In females, sensitivity was comparable for both agents. Specificity of MIBI planar and SPECT imaging was higher then for 201 TI (P: 90.9% v. 66.7%; S: 76.2% v. 61.9%). The improved imaging characteristics of MIBI results in better diagnostic confidence when interpreting myocardial perfusion studies especially in women and obese patients

  2. Tank vapor sampling and analysis data package for tank 241-C-106 waste retrieval sluicing system process test phase III

    Energy Technology Data Exchange (ETDEWEB)

    LOCKREM, L.L.

    1999-08-13

    This data package presents sampling data and analytical results from the March 28, 1999, vapor sampling of Hanford Site single-shell tank 241-C-106 during active sluicing. Samples were obtained from the 296-C-006 ventilation system stack and ambient air at several locations. Characterization Project Operations (CPO) was responsible for the collection of all SUMMATM canister samples. The Special Analytical Support (SAS) vapor team was responsible for the collection of all triple sorbent trap (TST), sorbent tube train (STT), polyurethane foam (PUF), and particulate filter samples collected at the 296-C-006 stack. The SAS vapor team used the non-electrical vapor sampling (NEVS) system to collect samples of the air, gases, and vapors from the 296-C-006 stack. The SAS vapor team collected and analyzed these samples for Lockheed Martin Hanford Corporation (LMHC) and Tank Waste Remediation System (TWRS) in accordance with the sampling and analytical requirements specified in the Waste Retrieval Sluicing System Vapor Sampling and Analysis Plan (SAP) for Evaluation of Organic Emissions, Process Test Phase III, HNF-4212, Rev. 0-A, (LMHC, 1999). All samples were stored in a secured Radioactive Materials Area (RMA) until the samples were radiologically released and received by SAS for analysis. The Waste Sampling and Characterization Facility (WSCF) performed the radiological analyses. The samples were received on April 5, 1999.

  3. Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer.

    Science.gov (United States)

    Katakami, Nobuyuki; Harada, Toshiyuki; Murata, Toru; Shinozaki, Katsunori; Tsutsumi, Masakazu; Yokota, Takaaki; Arai, Masatsugu; Tada, Yukio; Narabayashi, Masaru; Boku, Narikazu

    2017-12-01

    Purpose Opioid-induced constipation (OIC) is a frequent and debilitating adverse effect (AE) of opioids-common analgesics for cancer pain. We investigated the efficacy and safety of a peripherally acting μ-opioid receptor antagonist, naldemedine (S-297995), for OIC, specifically in patients with cancer. Patients and Methods This phase III trial consisted of a 2-week, randomized, double-blind, placebo-controlled study (COMPOSE-4) and an open-label, 12-week extension study (COMPOSE-5). In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned on a 1:1 basis to receive once-daily oral naldemedine 0.2 mg or placebo. The primary end point was the proportion of spontaneous bowel movement (SBM) responders (≥ 3 SBMs/week and an increase of ≥ 1 SBM/week from baseline). The primary end point of COMPOSE-5 was safety. Results In COMPOSE-4, 193 eligible patients were randomly assigned to naldemedine (n = 97) or placebo (n = 96). The proportion of SBM responders in COMPOSE-4 was significantly greater with naldemedine than with placebo (71.1% [69 of 97 patients] v 34.4% [33 of 96 patients]; P opioid withdrawal and had no notable impact on opioid-mediated analgesia. Conclusion Once-daily oral naldemedine 0.2 mg effectively treated OIC and was generally well tolerated in patients with OIC and cancer.

  4. Classification of criticality calculations with correlation coefficient method and its application to OECD/NEA burnup credit benchmarks phase III-A and II-A

    International Nuclear Information System (INIS)

    Okuno, Hiroshi

    2003-01-01

    A method for classifying benchmark results of criticality calculations according to similarity was proposed in this paper. After formulation of the method utilizing correlation coefficients, it was applied to burnup credit criticality benchmarks Phase III-A and II-A, which were conducted by the Expert Group on Burnup Credit Criticality Safety under auspices of the Nuclear Energy Agency of the Organisation for Economic Cooperation and Development (OECD/NEA). Phase III-A benchmark was a series of criticality calculations for irradiated Boiling Water Reactor (BWR) fuel assemblies, whereas Phase II-A benchmark was a suite of criticality calculations for irradiated Pressurized Water Reactor (PWR) fuel pins. These benchmark problems and their results were summarized. The correlation coefficients were calculated and sets of benchmark calculation results were classified according to the criterion that the values of the correlation coefficients were no less than 0.15 for Phase III-A and 0.10 for Phase II-A benchmarks. When a couple of benchmark calculation results belonged to the same group, one calculation result was found predictable from the other. An example was shown for each of the Benchmarks. While the evaluated nuclear data seemed the main factor for the classification, further investigations were required for finding other factors. (author)

  5. Novel solid phase extraction procedure for gold(III) on Dowex M 4195 prior to its flame atomic absorption spectrometric determination

    Energy Technology Data Exchange (ETDEWEB)

    Tuzen, Mustafa [Gaziosmanpasa University, Faculty of Science and Arts, Chemistry Department, 60250 Tokat (Turkey)], E-mail: mtuzen@gop.edu.tr; Saygi, Kadriye O. [Gaziosmanpasa University, Faculty of Science and Arts, Chemistry Department, 60250 Tokat (Turkey); Soylak, Mustafa [Erciyes University, Faculty of Science and Arts, Chemistry Department, 38039 Kayseri (Turkey)

    2008-08-15

    A method for solid phase extraction (SPE) of gold(III) using Dowex M 4195 chelating resin has been developed. The optimum experimental conditions for the quantitative sorption of gold(III), pH, effect of flow rates, eluent types, sorption capacity and the effect of diverse ions on the sorption of gold(III) have been investigated. The chelating resin can be reused for more than 100 cycles of sorption-desorption without any significant change in sorption of gold(III) ions. The recovery values for gold(III) and detection limit (LOD) of gold were greater than 95% and 1.61 {mu}g L{sup -1}, respectively. The preconcentration factor was 31. The relative standard deviation of the method was <5%. The adsorption capacity of the resin was 8.1 mg g{sup -1}. The proposed method has been applied for the determination of gold(III) in some real samples including water, soil and sediment samples.

  6. Tolerance and Acceptance Results of a Palladium-103 Permanent Breast Seed Implant Phase I/II Study

    International Nuclear Information System (INIS)

    Pignol, Jean-Philippe; Rakovitch, Eileen; Keller, Brian M.; Sankreacha, Raxa; Chartier, Carole

    2009-01-01

    Purpose: To test, in a prospective Phase I/II trial, a partial breast irradiation technique using a 103 Pd permanent breast seed implant (PBSI) realized in a single 1-h procedure under sedation and local freezing. Methods and Materials: Eligible patients had infiltrating ductal carcinoma ≤3 cm in diameter, surgical margin ≥2 mm, no extensive intraductal component, no lymphovascular invasion, and negative lymph nodes. Patients received a permanent seed implant, and a minimal peripheral dose of 90 Gy was prescribed to the clinical target volume, with a margin of 1.5 cm. Results: From May 2004 to April 2007, 67 patients received the PBSI treatment. The procedure was well tolerated, with 17% of patients having significant pain after the procedure. Only 1 patient (1.5%) had an acute skin reaction (Grade 3 according to the National Cancer Institute Common Toxicity Criteria). The rates of acute moist desquamation, erythema, and indurations were 10.4%, 42%, and 27%, respectively. At 1 year the rate of Grade 1 telangiectasia was 14%. The rate of skin reaction decreased from 65% to 28% when skin received less than the 85% isodose. According to a Radiation Therapy Oncology Group questionnaire, 80-90% of patients were very satisfied with their treatment, and the remainder were satisfied. One patient (1.5%) developed an abscess, which resolved after the use of antibiotics. There was no recurrence after a median follow-up of 32 months (range, 11-49 months). Conclusions: The feasibility, safety, and tolerability of PBSI compares favorably with that of external beam and other partial breast irradiation techniques.

  7. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    Energy Technology Data Exchange (ETDEWEB)

    Mimura, Hidefumi, E-mail: mimura@marianna-u.ac.jp [St. Marianna University School of Medicine, Department of Radiology (Japan); Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp [Mie University School of Medicine, Department of Interventional Radiology (Japan); Sone, Miyuki, E-mail: msone@me.com; Takeuchi, Yoshito, E-mail: yotake62@qg8.so-net.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Miki, Tsuneharu, E-mail: tmiki@koto.kpu-m.ac.jp [Kyoto Prefectural University of Medicine, Department of Urology (Japan); Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan); Sakuhara, Yusuke, E-mail: yusaku@med.hokudai.ac.jp [Hokkaido University School of Medicine, Department of Diagnostic and Interventional Radiology (Japan); Yamamoto, Takanobu, E-mail: tyamamot@tcc.pref.tochigi.lg.jp [Tochigi Cancer Center, Department of Radiology (Japan); Sato, Yozo, E-mail: ysato@aichi-cc.jp [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kanazawa, Susumu, E-mail: susumu@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan)

    2016-05-15

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  8. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    International Nuclear Information System (INIS)

    Mimura, Hidefumi; Arai, Yasuaki; Yamakado, Koichiro; Sone, Miyuki; Takeuchi, Yoshito; Miki, Tsuneharu; Gobara, Hideo; Sakuhara, Yusuke; Yamamoto, Takanobu; Sato, Yozo; Kanazawa, Susumu

    2016-01-01

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  9. PREVENTION OF CONVERSION TO ABNORMAL TCD WITH HYDROXYUREA IN SICKLE CELL ANEMIA: A PHASE III INTERNATIONAL RANDOMIZED CLINICAL TRIAL

    Science.gov (United States)

    Hankins, Jane S.; McCarville, M. Beth; Rankine-Mullings, Angela; Reid, Marvin E.; Lobo, Clarisse L.C.; Moura, Patricia G.; Ali, Susanna; Soares, Deanne; Aldred, Karen; Jay, Dennis W.; Aygun, Banu; Bennett, John; Kang, Guolian; Goldsmith, Jonathan C.; Smeltzer, Matthew P.; Boyett, James M.; Ware, Russell E.

    2015-01-01

    Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was an NHLBI-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ0-thalassemia (1), and HbSD (1), median age 5.4 years (range, 2.7-9.8)]. Due to slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI 0 to 35%) in the hydroxyurea arm and 47% (95% CI 6 to 81%) in observation arm at 15 months (p=0.16). In post-hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities, compared to observation (0% versus 50%, p=0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (−15.5 versus +10.2 cm/sec, p=0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. PMID:26414435

  10. Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial.

    Science.gov (United States)

    Hankins, Jane S; McCarville, Mary Beth; Rankine-Mullings, Angela; Reid, Marvin E; Lobo, Clarisse L C; Moura, Patricia G; Ali, Susanna; Soares, Deanne P; Aldred, Karen; Jay, Dennis W; Aygun, Banu; Bennett, John; Kang, Guolian; Goldsmith, Jonathan C; Smeltzer, Matthew P; Boyett, James M; Ware, Russell E

    2015-12-01

    Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ(0) -thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0-35%) in the hydroxyurea arm and 47% (95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. © 2015 Wiley Periodicals, Inc.

  11. Safety and tolerability of tegaserod in patients with chronic constipation: pooled data from two phase III studies.

    LENUS (Irish Health Repository)

    Quigley, Eamonn M M

    2012-02-03

    BACKGROUND & AIMS: Studies show that tegaserod effectively relieves the symptoms of chronic constipation\\/idiopathic constipation (CC). This pooled analysis assessed the safety and tolerability of tegaserod in a large dataset of CC patients. METHODS: Adverse event (AE) data were pooled from 2 double-blind, placebo-controlled phase III trials of 12 weeks\\' duration. Post hoc analysis was conducted for the most frequent AEs (incidence, >or=3%). RESULTS: Eight hundred eighty-one, 861, and 861 patients received tegaserod 6 mg twice a day, 2 mg twice a day, or placebo, respectively. Most AEs were mild\\/moderately severe. AE incidence was similar for the tegaserod 6 mg and 2 mg twice a day (57.1% and 56.3%, respectively) and placebo groups (59.6%) and most frequent in the gastrointestinal system (tegaserod 6 mg twice a day, 25.8%; 2 mg twice a day, 22.5%; placebo, 24.6%). Headache, the most common AE, was slightly more frequent in the placebo group (tegaserod 6 mg twice a day, 11.0%; 2 mg twice a day, 10.1%; placebo, 13.2%). Diarrhea (generally transient and resolved with continued treatment) was the only AE with a statistically significant difference between groups (tegaserod 6 mg twice a day 6.6% vs placebo 3.0%, P=.0005). Serious AE incidence (1.4% overall) was comparable across treatment groups, although abdominal surgery was less common in the combined tegaserod (0.5%) than the placebo group (1.0%). Discontinuation as a result of AEs was slightly higher in tegaserod 6 mg twice a day patients (5.7%; 2 mg twice a day, 3.3%; placebo, 3.7%), mainly because of diarrhea. Laboratory and electrocardiogram parameters were comparable across groups. CONCLUSIONS: Tegaserod is well tolerated by patients with CC during 12 weeks of treatment.

  12. Dosimetric explanations of fatigue in head and neck radiotherapy: An analysis from the PARSPORT Phase III trial

    International Nuclear Information System (INIS)

    Gulliford, Sarah L.; Miah, Aisha B.; Brennan, Sinead; McQuaid, Dualta; Clark, Catharine H.; Partridge, Mike; Harrington, Kevin J.; Morden, James P.; Hall, Emma; Nutting, Christopher M.

    2012-01-01

    Background: An unexpected finding from the phase III parotid sparing radiotherapy trial, PARSPORT (ISRCTN48243537, CRUK/03/005), was a statistically significant increase in acute fatigue for those patients who were treated with intensity-modulated radiotherapy (IMRT) compared to standard conventional radiotherapy (CRT). One possible explanation was the difference in dose to central nervous system (CNS) structures due to differing beam portals. Using data from the trial, a dosimetric analysis of individual CNS structures was performed. Method: Dosimetric and toxicity data were available for 67 patients (27 CRT, 40 IMRT). Retrospective delineation of the posterior fossa, brainstem, cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia was performed. Dosimetry was reviewed using summary statistics and dose–volume atlases. Results: A statistically significant increase in maximum and mean doses to each structure was observed for patients who received IMRT compared to those who received CRT. Both maximum and mean doses were significantly higher for the posterior fossa, brainstem and cerebellum for the 42 patients who reported acute fatigue of Grade 2 or higher (p ⩽ 0.01) compared to the 25 who did not. Dose–volume atlases of the same structures indicated that regions representing larger volumes and higher doses to each structure were consistent with a higher incidence of acute fatigue. There was no association between the dose distribution and acute fatigue for the other structures tested. Conclusions: The excess fatigue reported in the IMRT arm of the trial may, at least in part, be attributed to the dose distribution to the posterior fossa, cerebellum and brainstem. Future studies that modify dose delivery to these structures may allow us to test the hypothesis that radiation-induced fatigue is avoidable.

  13. A phase I/II study of Docetaxel/TS-1 with radiation for esophageal cancer patients. Step 1

    International Nuclear Information System (INIS)

    Matsumoto, Hideo; Hirai, Toshihiro; Hirabayashi, Youko

    2006-01-01

    The therapy 5-fluorouracil (FU) and cisplatin (CDDP) with radiation is thought to be the standard therapy for esophageal cancer patients by now. However, the therapy is associated with a comparatively high incidence of gastrointestinal disorders and requires hospitalization. We have proposed a new regimen of Docetaxel and TS-1 with radiation for maintaining of QOL and improving outcome. Step 1 of the clinical phase I/II study was conducted for 10 cases from May 2004 to March 2006. Treatment could be accomplished in all cases, and no treatment-related deaths or adverse events of grade 4 were observed in any case. As for hematotoxicity, one case had leucopenia of grade 3 and neutropenia of grade 2. As for non-hematotoxic adverse events, anorexia of grade 3 was recognized in one case of level 3. The response rate evaluated by RECIST was 66% (CR in 2 cases, PR in 4 cases,) and the rate based on the Guide Lines for the Clinical and Pathologic Studies on Carcinoma of Esophagus by the Japanese Society for Esophageal Cancer was 70% (CR in 3 cases, PR in 4 cases). We assumed that the recommended dosage of TXT was 30 mg/m 2 and that of TS-1 was 60 mg/m 2 with radiotherapy of 60 Gy. This combination therapy may be recommended because of fewer adverse events and a higher responsive rate than the standard therapies. We intend to continue this study to step 2 and 3, and to reveal the response rate and adverse events for more esophageal cancer patients. (author)

  14. A Multicenter Phase I/II Study of the BCNU Implant (Gliadel ® Wafer) for Japanese Patients with Malignant Gliomas

    Science.gov (United States)

    AOKI, Tomokazu; NISHIKAWA, Ryo; SUGIYAMA, Kazuhiko; NONOGUCHI, Naosuke; KAWABATA, Noriyuki; MISHIMA, Kazuhiko; ADACHI, Jun-ichi; KURISU, Kaoru; YAMASAKI, Fumiyuki; TOMINAGA, Teiji; KUMABE, Toshihiro; UEKI, Keisuke; HIGUCHI, Fumi; YAMAMOTO, Tetsuya; ISHIKAWA, Eiichi; TAKESHIMA, Hideo; YAMASHITA, Shinji; ARITA, Kazunori; HIRANO, Hirofumi; YAMADA, Shinobu; MATSUTANI, Masao

    2014-01-01

    Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe. PMID:24739422

  15. Bitopertin in Negative Symptoms of Schizophrenia-Results From the Phase III FlashLyte and DayLyte Studies.

    Science.gov (United States)

    Bugarski-Kirola, Dragana; Blaettler, Thomas; Arango, Celso; Fleischhacker, Wolfgang W; Garibaldi, George; Wang, Alice; Dixon, Mark; Bressan, Rodrigo A; Nasrallah, Henry; Lawrie, Stephen; Napieralski, Julie; Ochi-Lohmann, Tania; Reid, Carol; Marder, Stephen R

    2017-07-01

    There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising. Three (SunLyte [WN25308], DayLyte [WN25309], and FlashLyte [NN25310]) phase III, multicenter, randomized, 24-week, double-blind, parallel-group, placebo-controlled studies evaluated the efficacy and safety of adjunctive bitopertin in stable patients with persistent predominant negative symptoms of schizophrenia treated with antipsychotics. SunLyte met the prespecified criteria for lack of efficacy and was declared futile. Key inclusion criteria were age ≥18 years, DSM-IV-TR diagnosis of schizophrenia, score ≥40 on the sum of the 14 Positive and Negative Syndrome Scale negative symptoms and disorganized thought factors, unaltered antipsychotic treatment, and clinical stability. Following a 4-week prospective stabilization period, patients were randomly assigned 1:1:1 to bitopertin (5 mg and 10 mg [DayLyte] and 10 mg and 20 mg [FlashLyte]) or placebo once daily for 24 weeks. The primary efficacy end point was mean change from baseline in Positive and Negative Syndrome Scale negative symptom factor score at week 24. The intent-to-treat population in DayLyte and FlashLyte included 605 and 594 patients, respectively. At week 24, mean change from baseline showed improvement in all treatment arms but no statistically significant separation from placebo in Positive and Negative Syndrome Scale negative symptom factor score and all other end points. Bitopertin was well tolerated. These studies provide no evidence for superior efficacy of adjunctive bitopertin in any of the doses tested over placebo in patients with persistent predominant negative symptoms of schizophrenia. Copyright © 2017. Published by Elsevier Inc.

  16. Effectiveness of cellulose sulfate vaginal gel for the prevention of HIV infection: results of a Phase III trial in Nigeria.

    Directory of Open Access Journals (Sweden)

    Vera Halpern

    Full Text Available This trial evaluated the safety and effectiveness of 6% cellulose sulfate vaginal gel in preventing male-to-female vaginal transmission of HIV, gonorrhea and chlamydial infection.This Phase III, double-blind, randomized, placebo-controlled trial was conducted between November 2004 and March 2007 in Lagos and Port Harcourt, Nigeria. We enrolled 1644 HIV-antibody negative women at high risk of HIV acquisition. Study participants were randomized 1:1 to cellulose sulfate or placebo and asked to use gel plus a condom for each act of vaginal intercourse over one year of follow-up. The participants were evaluated monthly for HIV, gonorrhea and chlamydial infection, and for adverse events.The trial was stopped prematurely after the data safety monitoring board of a parallel trial concluded that cellulose sulfate might be increasing the risk of HIV. In contrast, we observed fewer infections in the active arm (10 than on placebo (13, a difference that was nonetheless not statistically significant (HR = 0.8, 95% CI 0.3-1.8; p = 0.56. Rates of gonorrhea and chlamydial infection were lower in the CS group but the difference was likewise not statistically significant (HR = 0.8, 95% CI 0.5-1.1; p = 0.19 for the combined STI outcome. Rates of adverse events were similar across study arms. No serious adverse events related to cellulose sulfate use were reported.Cellulose sulfate gel appeared to be safe in the evaluated study population but we found insufficient evidence that it prevented male-to-female vaginal transmission of HIV, gonorrhea or chlamydial infection. The early closure of the trial compromised the ability to draw definitive conclusions about the effectiveness of cellulose sulfate against HIV.ClinicalTrials.gov NCT00120770.

  17. 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.

  18. Implementation of a Novel Adherence Monitoring Strategy in a Phase III, Blinded, Placebo-Controlled, HIV-1 Prevention Clinical Trial.

    Science.gov (United States)

    Husnik, Marla J; Brown, Elizabeth R; Marzinke, Mark; Livant, Edward; Palanee-Phillips, Thesla; Hendrix, Craig W; Matovu Kiweewa, Flavia; Nair, Gonasagrie; Soto-Torres, Lydia E; Schwartz, Katie; Hillier, Sharon L; Baeten, Jared M

    2017-11-01

    Placebo-controlled HIV-1 prevention trials of pre-exposure prophylaxis (PrEP) have not generally used concurrent measurement of adherence because of the potential risk of unblinding. However, several pre-exposure prophylaxis trials for HIV-1 prevention among women failed to show effectiveness because of low product adherence. Evaluation of product adherence objectively during a study provides the opportunity for strengthening adherence activities at sites having low adherence. During MTN-020/ASPIRE, a phase III, placebo-controlled trial of the dapivirine intravaginal ring, we implemented an adherence monitoring system. Monitoring began in quarter 1 (Q1) 2013 and continued through the conclusion of the trial. Blood plasma was collected quarterly and tested for dapivirine concentrations while maintaining blinding among study team members involved in participant management. Dapivirine concentrations >95 pg/mL, reflecting >8 hours of continuous use, were assessed as signaling product use. Study leadership monitored results on a monthly basis and provided feedback to site investigators. Experiences were shared across sites to motivate staff and counsel participants to strive toward higher adherence levels. An upward trend in adherence was observed (P dapivirine >95 pg/mL increased from 63% in Q1 2013 to 84% by Q1 2015. Ongoing drug level testing as a marker of adherence in MTN-020/ASPIRE demonstrates the feasibility of real-time adherence monitoring while maintaining study blinding at the level of participants, sites, and study leadership. This approach is novel for large-scale effectiveness studies for HIV-1 prevention.

  19. Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial

    Science.gov (United States)

    Hacker, Ulrich T; Escalona-Espinosa, Laura; Consalvo, Nicola; Goede, Valentin; Schiffmann, Lars; Scherer, Stefan J; Hedge, Priti; Van Cutsem, Eric; Coutelle, Oliver; Büning, Hildegard

    2016-01-01

    Background: In the phase III AVAGAST trial, the addition of bevacizumab to chemotherapy improved progression-free survival (PFS) but not overall survival (OS) in patients with advanced gastric cancer. We studied the role of Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and resistance to antiangiogenic treatment, as a biomarker. Methods: Previously untreated, advanced gastric cancer patients were randomly assigned to receive bevacizumab (n=387) or placebo (n=387) in combination with chemotherapy. Plasma collected at baseline and at progression was analysed by ELISA. The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model. Logistic regression analysis was applied for correlations with metastasis. Results: Median baseline plasma Ang-2 levels were lower in Asian (2143 pg ml−1) vs non-Asian patients (3193 pg ml−1), P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver metastasis (LM) at any time: Odds ratio per 1000 pg ml−1 increase: 1.19; 95% CI 1.10–1.29; P<0.0001 (non-Asians) and 1.37; 95% CI 1.13–1.64; P=0.0010 (Asians). Conclusions: Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM. Differences in Ang-2 mediated vascular response may, in part, account for outcome differences between Asian and non-Asian patients; however, data have to be further validated. Ang-2 is a promising drug target in gastric cancer. PMID:27031850

  20. Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study.

    Science.gov (United States)

    Cukras, Catherine A; Petrou, Philip; Chew, Emily Y; Meyerle, Catherine B; Wong, Wai T

    2012-06-22

    Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME. A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA). Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors. In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.).

  1. Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India.

    Science.gov (United States)

    John, Jacob; Kawade, Anand; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; Bhandari, Nita; Taneja, Sunita; Antony, Kalpana; Bhatnagar, Veereshwar; Gupta, Arun; Kabra, Madhulika; Kang, Gagandeep

    2014-08-11

    Post licensure studies have identified an increased risk of intussusception following vaccination with currently licensed rotavirus vaccines, raising safety concerns generic to all rotavirus vaccines. We describe the surveillance for intussusception in a phase III clinical trial with an oral monovalent rotavirus vaccine developed from the neonatal 116E strain. Using broad screening criteria and active surveillance, the incidence of intussusception between 6 weeks and 2 years of age was measured in 4532 children who received three doses of vaccine and 2267 children who received a placebo in the clinical trial. Possible intussusceptions were evaluated with a screening ultrasonogram. An independent intussusception case adjudication committee reviewed all intussusceptions and graded them on Brighton Collaboration criteria for diagnostic certainty. We identified twenty-three intussusceptions on ultrasound from 1361 evaluated sentinel events. Eleven were of level 1 diagnostic certainty as determined by the independent intussusception case adjudication committee. None required surgical intervention, and the earliest identified intussusception was at 36 days following the third dose in a placebo recipient. Among vaccine recipients the first event of intussusception occurred 112 days after the third dose. The incidence of ultrasound-diagnosed intussusception was 200/100,000 child-years (95% CI, 120, 320) among those receiving the vaccine and 141/100,000 child-years (95% CI, 50, 310) among those receiving the placebo. The incidence rate of confirmed intussusception among vaccine recipients was 94/100,000 child-years (95% CI, 41, 185) and 71/100,000 child-years (95% CI, 15, 206) among those receiving the placebo. In this licensure study, 23 cases of intussusception were identified through an active surveillance system, but there was no temporal association with rotavirus vaccination. The use of active surveillance with broad criteria intended for ensuring safety of children

  2. Phase II/III Study of Radiofrequency Ablation Combined with Cytokine-Induced Killer Cells Treating Colorectal Liver Metastases

    Directory of Open Access Journals (Sweden)

    Xiaodong Li

    2016-11-01

    Full Text Available Purpose: This phase II/III, non-randomized clinical trial aimed to determine the efficacy and safety of the combination of radiofrequency ablation (RFA and cytokine-induced killer (CIK cells transfusion for patients with colorectal liver metastases (CRLMs. Experimental Design: A total of 60 eligible patients with CRLMs were enrolled and divided into Group A (RFA alone, n = 30 and Group B (RFA plus CIK, n = 30, and following enzyme-linked immunosorbent spot assay was performed in 8 patients with CEA > 50 ng/mL pre-RFA and 7 days post-RFA and CIK treatment, respectively. Results: The median progression-free survival (PFS times of Group A and Group B were 18.5 months and 23 months, respectively (P = 0.0336. The 3-year progression-free rates were 13.3% in Group A and 20.3% in Group B, respectively. The median overall survival time was 43 months in Group A, and not reached in Group B. The 3-year survival rates were 64.6% in Group A and 81.0% in Group B, respectively (P = 0.1187. Among the 8 patients with CEA > 50ng/mL, 6 had increase of circulating CEA-specific T cells after RFA (P = 0.010. After CIK cell therapy, the number of CEA-specific T cells increased in all the 8 patients comparing with that pre-treatment (P = 0.001 and in 7 patients comparing with that post-RFA (P = 0.028. Conclusions: We firstly confirm that the combination of RFA and CIK cells boosts CEA-specific T cell response and shows to be an efficacious and safe treatment modality for patients with CRLMs.

  3. An overview of the MIZ-1 borehole investigations during phase I/II. MIZ-1 progress report 03-01

    International Nuclear Information System (INIS)

    Ota, Kunio; Takeuchi, Shinji; Ikeda, Koki

    2004-05-01

    Surface-based investigations have now been carried out, in a step-by-step fashion, with the main aims of the development of conceptual models of the geological environment and the enhancement of the understanding of the undisturbed deep geological environment before excavation of the shafts and experimental drifts. The MIZ-1 borehole investigation programme was launched in December 2002, as a step of the field investigations at the MIU Construction Site. The overall goals of the MIZ-1 borehole investigations are to characterise the geological environment from the surface to over 1,000 m depth in the crystalline basement, to establish baseline conditions before excavation of the shafts and experimental drifts, and to provide a deep borehole for observing hydraulic responses during the shaft and drift excavation and experiments in the drifts during the Construction and the Operation Phases. The borehole is planned to be drilled in an overall south-westerly direction from the north-eastern area of the MIU Site. The planned inclination varies from vertical at shallower depths to 12deg from vertical at greater depths down to 1,350 m along the borehole length, which will be achieved by controlled directional drilling. In MIZ-1 Phase I/II (from March to May 2003), the borehole was drilled vertically, through the entire sedimentary formations, down to 123.00 m in the uppermost part of the Toki granite at the MIU Construction Site. The new method of wireline core drilling with a downhole motor was introduced for the drilling. Planned geological, geophysical and hydrochemical investigations and complementary hydraulic and hydrochemical monitoring were performed. In addition, as a complete loss of drilling fluid was encountered at 115.85 m along the borehole length, modified work procedures resulted in the execution of hydraulic tests with groundwater sampling, from necessity, in that section and of further drilling work. The local QC system was applied to all the

  4. Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT).

    Science.gov (United States)

    Carvajal, Richard D; Piperno-Neumann, Sophie; Kapiteijn, Ellen; Chapman, Paul B; Frank, Stephen; Joshua, Anthony M; Piulats, Josep M; Wolter, Pascal; Cocquyt, Veronique; Chmielowski, Bartosz; Evans, T R Jeffry; Gastaud, Lauris; Linette, Gerald; Berking, Carola; Schachter, Jacob; Rodrigues, Manuel J; Shoushtari, Alexander N; Clemett, Delyth; Ghiorghiu, Dana; Mariani, Gabriella; Spratt, Shirley; Lovick, Susan; Barker, Peter; Kilgour, Elaine; Lai, Zhongwu; Schwartz, Gary K; Nathan, Paul

    2018-04-20

    Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial ( ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m 2 intravenously on day 1 of every 21-day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by blinded independent central radiologic review. Secondary end points included overall survival and objective response rate. Results A total of 129 patients were randomly assigned to receive selumetinib plus dacarbazine (n = 97) or placebo plus dacarbazine (n = 32). In the selumetinib plus dacarbazine group, 82 patients (85%) experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine group (median, 2.8 v 1.8 months); the hazard ratio for PFS was 0.78 (95% CI, 0.48 to 1.27; two-sided P = .32). The objective response rate was 3% with selumetinib plus dacarbazine and 0% with placebo plus dacarbazine (two-sided P = .36). At 37% maturity (n = 48 deaths), analysis of overall survival gave a hazard ratio of 0.75 (95% CI, 0.39 to 1.46; two-sided P = .40). The most frequently reported adverse events (selumetinib plus dacarbazine v placebo plus dacarbazine) were nausea (62% v 19%), rash (57% v 6%), fatigue (44% v 47%), diarrhea (44% v 22%), and peripheral edema (43% v 6%). Conclusion In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had a tolerable safety

  5. Time to Angiographic Reperfusion and Clinical Outcome after Acute Ischemic Stroke in the Interventional Management of Stroke Phase III (IMS III) Trial: A Validation Study

    Science.gov (United States)

    Khatri, Pooja; Yeatts, Sharon D.; Mazighi, Mikael; Broderick, Joseph P.; Liebeskind, David S.; Demchuk, Andrew M.; Amarenco, Pierre; Carrozzella, Janice; Spilker, Judith; Foster, Lydia D.; Goyal, Mayank; Hill, Michael D.; Palesch, Yuko Y.; Jauch, Edward C.; Haley, E. Clarke; Vagal, Achala; Tomsick, Thomas A.

    2014-01-01

    BACKGROUND The IMS III Trial did not demonstrate clinical benefit of the endovascular approach compared to IV rt-PA alone for moderate or severe ischemic strokes (NIHSS≥8) enrolled within three hours of stroke onset. Late reperfusion of tissue that is no longer salvageable may be one explanation, as suggested by prior exploratory studies showing an association between time to reperfusion and good clinical outcome. We sought to validate this relationship in the large-scale IMS III trial, and consider its implications for future endovascular trials. METHODS The analysis consisted of the endovascular cohort with proximal arterial occlusions in the anterior circulation that achieved angiographic reperfusion (TICI 2–3) during the endovascular procedure (within 7 hours from the onset of symptoms). Logistic regression was used to model good clinical outcome (90-day modified Rankin 0–2) as a function of the time to reperfusion, and prespecified variables were considered for adjustment. FINDINGS Among 240 proximal vessel occlusions, angiographic reperfusion (TICI 2–3) was achieved in 182 (76%). Mean time to reperfusion was 325 minutes (range 180–418 minutes). Longer time for reperfusion was associated with a decreased likelihood of good clinical outcome (RR [95% CI] for every 30 minute delay: unadjusted 0·85 [0·77–0·94]; adjusted 0·88 [0·80–0·98]). INTERPRETATION We confirm that delay in time to angiographic reperfusion leads to a decreased likelihood of good clinical outcome. Achieving rapid reperfusion may be critical for the successes of future acute endovascular trials. FUNDING: NIH/NINDS (study sponsor), Genentech Inc. (study drug - intra-arterial t-PA), EKOS Corp. (device), Concentric Inc. (device), Cordis Neurovascular, Inc. (device), and Boehringer Ingelheim (European Investigator Meeting support). PMID:24784550

  6. Repair and fixation of potentially lethal damage (PLD) as demonstrated by delayed plating or incubation with araA in contact inhibited refed plateau-phase C3H mouse embryo 10T1/2 cells grown in the presence of BrdUrd

    International Nuclear Information System (INIS)

    Iliakis, G.; Wright, E.; Ngo, F.Q.H.

    1987-01-01

    CH3 mouse 10 T 1/2 cells showing strong inhibition of growth at confluency were grown under daily refeeding in the presence of BrdUrd (from 0 to 1 μM) and exposed to γ-rays either while exponentially growing or in the plateau phase. An increase in radiosensitivity was observed in both growth conditions mainly reflected by a reduction in Dq. Greater radiosensitization was observed in exponentially growing than in plateau-phase cells, and 3-4 times higher BrdUrd concentrations were required in plateau-phase cells for similar potentiation in killing. This effect could not be entirely attributed to a reduction in BrdUrd incorporation since measurements with 3 H-BrdUrd showed reductions in incorporation between only 17-47% in plateau-phase cells. The rate of repair of potentially lethal damage (PLD) as demonstrated by delayed plating was not affected by the incorporation of BrdUrd, but the amount of repair (measured as the relative increase in cell survival) was higher for BrdUrd containing cells. Post-irradiation treatment of cells in the plateau-phase (no BrdUrd) with 9-β-D-arabinofuranosyladenine (araA) caused fixation of radiation-induced PLD. AraA treatment of cells grown in the presence of various amounts of BrdUrd also caused fixation of PLD, but resulted in survival levels similar to those observed with cells growing in BrdUrd-free medium. This result indicates that BrdUrd mediated radiosensitization cannot be observed when cells are prevented from repairing PLD by postirradiation incubation with araA. Based on these findings we propose that the mechanism of radiosensitization by BrdUrd incorporation might be, by increasing probability of fixation, mediated by the postirrdiation progression of cells through the cycle, of a sector of PLD also sensitive to post-irradiation treatment with araA. For this sector of PLD the term α-PLD has been proposed. (orig.)

  7. Structural systematics of rare earth complexes. III. Structural characterization of lanthanoid (III) picrate hydrates: gadolinium picrate dodecahydrate - an x-ray-induced phase modifications? - and some general aspects of structural chemistry of lanthanoid picrates

    International Nuclear Information System (INIS)

    Harrowfield, J.M.; Weimin, Lu; Brian, W.S.; White, A.H.

    1994-01-01

    In the course of the previous studies (Parts I and II), an unusual result was observed in the case of the structure determination of hydrated gadolinium(III) picrate. Midway through data collection, the monoclinic P2 1 /c phase modification (X-ray-induced?) to a similar cell more nearly resembling that of the La→Pr structure type recorded previously, with no loss of crystal integrity, and with useful data sets being obtained on both forms. Redetermination of the structure with a fresh sample yielded no reproduction of the anomaly. These results are recorded and discussed, together with an overview of the consequences of the data of Parts I-III in relation to those of other literature in the field. 13 refs., 4 tabs., 1 fig

  8. Adjuvant whole abdominal intensity modulated radiotherapy (IMRT) for high risk stage FIGO III patients with ovarian cancer (OVAR-IMRT-01) – Pilot trial of a phase I/II study: study protocol

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Jensen, Alexandra D; Sterzing, Florian; Munter, Marc W; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

    2007-01-01

    The prognosis for patients with advanced epithelial ovarian cancer remains poor despite aggressive surgical resection and platinum-based chemotherapy. More than 60% of patients will develop recurrent disease, principally intraperitoneal, and die within 5 years. The use of whole abdominal irradiation (WAI) as consolidation therapy would appear to be a logical strategy given its ability to sterilize small tumour volumes. Despite the clinically proven efficacy of whole abdominal irradiation, the use of radiotherapy in ovarian cancer has profoundly decreased mainly due to high treatment-related toxicity. Modern intensity-modulated radiation therapy (IMRT) could allow to spare kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. The OVAR-IMRT-01 study is a single center pilot trial of a phase I/II study. Patients with advanced ovarian cancer stage FIGO III (R1 or R2< 1 cm) after surgical resection and platinum-based chemotherapy will be treated with whole abdomen irradiation as consolidation therapy using intensity modulated radiation therapy (IMRT) to a total dose of 30 Gy in 1.5 Gy fractions. A total of 8 patients will be included in this trial. For treatment planning bone marrow, kidneys, liver, spinal cord, vertebral bodies and pelvic bones are defined as organs at risk. The planning target volume includes the entire peritoneal cavity plus pelvic and para-aortic node regions. The primary endpoint of the study is the evaluation of the feasibility of intensity-modulated WAI and the evaluation of the study protocol. Secondary endpoint is evaluation of the toxicity of intensity modulated WAI before continuing with the phase I/II study. The aim is to explore the potential of IMRT as a new method for WAI to decrease the dose to kidneys, liver, bone marrow while covering the peritoneal cavity with a homogenous dose, and to implement whole abdominal intensity-modulated radiotherapy into the adjuvant multimodal

  9. Zwitterion-functionalized polymer microspheres as a sorbent for solid phase extraction of trace levels of V(V), Cr(III), As(III), Sn(IV), Sb(III) and Hg(II) prior to their determination by ICP-MS.

    Science.gov (United States)

    Jia, Xiaoyu; Gong, Dirong; Zhao, Junyi; Ren, Hongyun; Wang, Jiani; Zhang, Xian

    2018-03-19

    This paper describes the preparation of zwitterion-functionalized polymer microspheres (ZPMs) and their application to simultaneous enrichment of V(V), Cr(III), As(III), Sn(IV), Sb(III) and Hg(II) from environmental water samples. The ZPMs were prepared by emulsion copolymerization of ethyl methacrylate, 2-diethylaminoethyl methacrylate and triethylene glycol dimethyl acrylate followed by modification with 1,3-propanesultone. The components were analyzed by elemental analyses as well as Fourier transform infrared spectroscopy, and the structures were characterized by scanning electron microscopy and transmission electron microscopy. The ZPMs were packed into a mini-column for on-line solid-phase extraction (SPE) of the above metal ions. Following extraction with 40 mM NH 4 NO 3 and 0.5 M HNO 3 solution, the ions were quantified by ICP-MS. Under the optimized conditions, the enrichment factors (from a 40 mL sample) are up to 60 for the ions V(V), As(III), Sb(III) and Hg(II), and 55 for Cr(III) and Sn(IV). The detection limits are 1.2, 3.4, 1.0, 3.7, 2.1 and 1.6 ng L -1 for V(V), Cr(III), As(III), Sn(IV), Sb(III) and Hg(II), respectively, and the relative standard deviations (RSDs) are below 5.2%. The feasibility and accuracy of the method were validated by successfully analyzing six certified reference materials as well as lake, well and river waters. Graphical abstract Zwitterion-functionalized polymer microspheres (ZPMs) were prepared and packed into a mini-column for on-line solid-phase extraction (SPE) via pump 1. Then V(V), Cr(III), As(III), Sn(IV), Sb(III) and Hg(II) ions in environmental waters were eluted and submitted to ICP-MS via pump 2.

  10. Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial.

    Science.gov (United States)

    Dey, Mahua; Stadnik, Agnieszka; Riad, Fady; Zhang, Lingjiao; McBee, Nichol; Kase, Carlos; Carhuapoma, J Ricardo; Ram, Malathi; Lane, Karen; Ostapkovich, Noeleen; Aldrich, Francois; Aldrich, Charlene; Jallo, Jack; Butcher, Ken; Snider, Ryan; Hanley, Daniel; Ziai, Wendy; Awad, Issam A

    2015-03-01

    Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication. To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature. Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software. Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis. Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to >60 trial sites.

  11. Impact of baseline covariates on the immunogenicity of the 9-valent HPV vaccine - A combined analysis of five phase III clinical trials

    DEFF Research Database (Denmark)

    Petersen, Lone K; Restrepo, Jaime; Moreira, Edson D

    2017-01-01

    BACKGROUND: The immunogenicity profile of the 9-valent HPV (9vHPV) vaccine was evaluated across five phase III clinical studies conducted in girls and boys 9-15 years of age and young women 16-26 years of age. The effect of baseline characteristics of subjects on vaccine-induced HPV antibody...... responses was assessed. METHODS: Immunogenicity data from 11,304 subjects who received ≥1 dose of 9vHPV vaccine in five Phase III studies were analyzed. Vaccine was administered as a 3-dose regimen. HPV antibody titers were assessed 1 month after dose 3 using a competitive Luminex immunoassay and summarized...... as geometric mean titers (GMTs). Covariates examined were age, gender, race, region of residence, and HPV serostatus and PCR status at day 1. RESULTS: GMTs to all 9 vaccine HPV types decreased with age at vaccination initiation, and were otherwise generally similar among the demographic subgroups defined...

  12. 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....

  13. 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

  14. Preliminary results of a phase I/II study of HDR brachytherapy alone for T1/T2 breast cancer

    International Nuclear Information System (INIS)

    Wazer, David E.; Berle, Lisa; Graham, Roger; Chung, Maureen; Rothschild, Janice; Graves, Theresa; Cady, Blake; Ulin, Kenneth; Ruthazer, Robin; DiPetrillo, Thomas A.

    2002-01-01

    Purpose: To investigate the feasibility, toxicity, cosmetic outcome, and local control of high-dose-rate (HDR) brachytherapy alone without whole breast external beam irradiation for early-stage breast carcinoma. Methods and Materials: Between June 1997 and August 1999, 32 women diagnosed with a total of 33 AJCC Stage I/II breast carcinomas underwent surgical breast excision and postoperative irradiation using HDR brachytherapy interstitial implantation as part of a multi-institutional clinical Phase I/II protocol. Eligible patients included those with T1, T2, N0, N1 (≤3 nodes positive), and M0 tumors of nonlobular histologic features with negative surgical margins, no extracapsular lymph node extension, and a negative postexcision mammogram. Brachytherapy catheters were placed at the initial excision, reexcision, or either sentinel or full-axillary sampling. Direct visualization, surgical clips, and ultrasound and/or CT scan assisted in the delineation of the target volume, defined as the excision cavity plus a 2-cm margin. High-activity 192 Ir (3-10 Ci) was used to deliver 340 cGy/fraction, 2 fractions/d, for 5 consecutive days, to a total dose of 34 Gy to the target volume. Source position and dwell times were calculated using standard volume optimization techniques. Results: The median follow-up of all patients was 33 months, and the mean patient age was 63 years. The mean tumor size was 1.3 cm, and 55% had an extensive intraductal component. Three patients had positive axillary nodes. Two patients experienced moderate perioperative pain that required narcotic analgesics. No peri- or postoperative infections occurred. No wound healing problems and no significant skin reactions related to the implant developed. The Radiation Therapy Oncology Group late radiation morbidity scoring scheme was applied to the entire 33-case cohort. In the assessment of the skin, 30 cases were Grade 0-1 and 3 cases were Grade 2. Subcutaneous toxicity was scored as 11 patients with

  15. Effect of silodosin on specific urinary symptoms associated with benign prostatic hyperplasia: analysis of international prostate symptom scores in 2 phase III clinical studies

    OpenAIRE

    Gittelman, Marc C; Marks, Leonard S; Hill, Lawrence A; Volinn, Weining; Hoel, Gary

    2010-01-01

    Marc C Gittelman1, Leonard S Marks2, Lawrence A Hill3, Weining Volinn3, Gary Hoel31South Florida Medical Research, Aventura, Florida, USA; 2University of California at Los Angeles and Urological Sciences Research Foundation, Los Angeles, California, USA; 3Watson Laboratories, Salt Lake City, Utah, USAPurpose: Pooled results from 2 randomized, placebo-controlled, US phase III studies (NCT00224107, NCT00224120) showed that silodosin, a uroselective α-blocker, significantly improved In...

  16. Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

    Science.gov (United States)

    Zhang, Sheng; Liang, Fei; Li, Wenfeng

    2017-11-01

    The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The Combination Process for Preparative Separation and Purification of Paclitaxel and 10-Deacetylbaccatin III Using Diaion® Hp-20 Followed by Hydrophilic Interaction Based Solid Phase Extraction

    Science.gov (United States)

    Shirshekanb, Mahsa; Rezadoost, Hassan; Javanbakht, Mehran; Ghassempour, Ali Reza

    2017-01-01

    There is no other naturally occurring defense agent against cancer that has a stronger effect than paclitaxel, commonly known under the brand name of Taxol®. The major drawback for the more widespread use of paclitaxel and its precious precursor, 10-deacetylbaccatin III (10-DAB III), is that they require large-scale extraction from different parts of yew trees (Taxus species), cell cultures, taxane-producing endophytic fungi, and Corylus species. In our previous work, a novel online two-dimensional heart-cut liquid chromatography process using hydrophilic interaction/ reversed-phase chromatography was used to introduce a semi-preparative treatment for the separation of polar (10-deacetylbaccatin III) and non-polar (paclitaxel) taxanes from Taxus baccata L. In this work, a combination of the absorbent (Diaion® HP-20) and a silica based solid phase extraction is utilized as a new, efficient, and cost effective method for large-scale production of taxanes. This process avoids the technical problem of two-dimensional preparative liquid chromatography. The first stage of the process involves discarding co-extractive polar compounds including chlorophylls and pigments using a non-polar synthetic hydrophobic absorbent, Diaion® HP-20. Extract was then loaded on to a silica based hydrophilic interaction solid phase extraction (silica 40-60 micron). Taxanes was eluted using a mixture of water and methanol at the optimized ratio of 70:30. Finally, the fraction containing taxanes was applied to semi-preparative reversed phase HPLC. The results revealed that using this procedure, paclitaxel and 10-DAB III could be obtained at 8 and 3 times more, respectively than by the traditional method of extraction. PMID:29552048

  18. The Combination Process for Preparative Separation and Purification of Paclitaxel and 10-Deacetylbaccatin III Using Diaion® Hp-20 Followed by Hydrophilic Interaction Based Solid Phase Extraction.

    Science.gov (United States)

    Shirshekanb, Mahsa; Rezadoost, Hassan; Javanbakht, Mehran; Ghassempour, Ali Reza

    2017-01-01

    There is no other naturally occurring defense agent against cancer that has a stronger effect than paclitaxel, commonly known under the brand name of Taxol ® . The major drawback for the more widespread use of paclitaxel and its precious precursor, 10-deacetylbaccatin III (10-DAB III), is that they require large-scale extraction from different parts of yew trees ( Taxus species), cell cultures, taxane-producing endophytic fungi, and Corylus species. In our previous work, a novel online two-dimensional heart-cut liquid chromatography process using hydrophilic interaction/ reversed-phase chromatography was used to introduce a semi-preparative treatment for the separation of polar (10-deacetylbaccatin III) and non-polar (paclitaxel) taxanes from Taxus baccata L. In this work, a combination of the absorbent (Diaion ®  HP-20) and a silica based solid phase extraction is utilized as a new, efficient, and cost effective method for large-scale production of taxanes. This process avoids the technical problem of two-dimensional preparative liquid chromatography. The first stage of the process involves discarding co-extractive polar compounds including chlorophylls and pigments using a non-polar synthetic hydrophobic absorbent, Diaion ®  HP-20. Extract was then loaded on to a silica based hydrophilic interaction solid phase extraction (silica 40-60 micron). Taxanes was eluted using a mixture of water and methanol at the optimized ratio of 70:30. Finally, the fraction containing taxanes was applied to semi-preparative reversed phase HPLC. The results revealed that using this procedure, paclitaxel and 10-DAB III could be obtained at 8 and 3 times more, respectively than by the traditional method of extraction.

  19. Analysis of Regional Timelines To Set Up a Global Phase III Clinical Trial in Breast Cancer: the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Experience

    OpenAIRE

    Metzger-Filho, Otto; Azambuja, Evandro de; Bradbury, Ian; Saini, Kamal S.; Bines, Jose; Simon, Sergio D. [UNIFESP; Van Dooren, Veerle; Aktan, Gursel; Pritchard, Kathleen I.; Wolff, Antonio C.; Smith, Ian; Jackisch, Christian; Lang, Istvan; Untch, Michael; Boyle, Frances

    2013-01-01

    Purpose. This study measured the time taken for setting up the different facets of Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), an international phase III study being conducted in 44 participating countries.Methods. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected i...

  20. Opioid Patient Controlled Analgesia (PCA) use during the Initial Experience with the IMPROVE PCA Trial: A Phase III Analgesic Trial for Hospitalized Sickle Cell Patients with Painful Episodes

    OpenAIRE

    Dampier, Carlton D.; Smith, Wally R.; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C.; Minniti, Caterina P.; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A. Kyle; McClish, Donna; McKinlay, Sonja M.; Miller, Scott T.; Osunkwo, Ifeyinwa; Seaman, Phillip

    2011-01-01

    Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher const...

  1. CENTRAL PLATEAU REMEDIATION OPTIMIZATION STUDY

    Energy Technology Data Exchange (ETDEWEB)

    BERGMAN, T. B.; STEFANSKI, L. D.; SEELEY, P. N.; ZINSLI, L. C.; CUSACK, L. J.

    2012-09-19

    THE CENTRAL PLATEAU REMEDIATION OPTIMIZATION STUDY WAS CONDUCTED TO DEVELOP AN OPTIMAL SEQUENCE OF REMEDIATION ACTIVITIES IMPLEMENTING THE CERCLA DECISION ON THE CENTRAL PLATEAU. THE STUDY DEFINES A SEQUENCE OF ACTIVITIES THAT RESULT IN AN EFFECTIVE USE OF RESOURCES FROM A STRATEGIC PERSPECTIVE WHEN CONSIDERING EQUIPMENT PROCUREMENT AND STAGING, WORKFORCE MOBILIZATION/DEMOBILIZATION, WORKFORCE LEVELING, WORKFORCE SKILL-MIX, AND OTHER REMEDIATION/DISPOSITION PROJECT EXECUTION PARAMETERS.

  2. Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

    Directory of Open Access Journals (Sweden)

    Nativ Ofer

    2012-11-01

    Full Text Available Abstract Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10, and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC-controlled Phase I/II study (N = 7 in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10: All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7: Hemostatic success at 10 min (primary endpoint was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial

  3. Project 8, Phase III Design: Placing an eV-Scale Limit on the Neutrino Mass using Cyclotron Radiation Emission Spectroscopy

    Science.gov (United States)

    Oblath, Noah; Project 8 Collaboration

    2016-09-01

    We report on the design concept for Phase III of the Project 8 experiment. In the third phase of Project 8 we aim to place a limit on the neutrino mass that is similar to the current limits set by tritium beta-decay experiments, mν radioastronomy will be employed to search for and track electron signals in the fiducial volume. This talk will present the quantitative design concept for the phased-array receiver, and illustrate how we are progressing towards the Phase IV experiment, which will have sensitivity to the neutrino mass scale allowed by the inverted mass hierarchy. This work is supported by the DOE Office of Science Early Career Research Program, and the Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory.

  4. Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial

    International Nuclear Information System (INIS)

    Fogarty, Gerald; Shivalingam, Brindha; Dhillon, Haryana; Thompson, John F; Morton, Rachael L; Vardy, Janette; Nowak, Anna K; Mandel, Catherine; Forder, Peta M; Hong, Angela; Hruby, George; Burmeister, Bryan

    2011-01-01

    Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete. This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function. Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain

  5. A phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer

    International Nuclear Information System (INIS)

    Newton, Robert U; Taaffe, Dennis R; Spry, Nigel; Gardiner, Robert A; Levin, Gregory; Wall, Bradley; Joseph, David; Chambers, Suzanne K; Galvão, Daniel A

    2009-01-01

    targeting bone density, cardiovascular function, lean and fat mass, physical function and falls risk as primary study endpoints. In terms of advancement of prostate cancer care, we expect dissemination of the knowledge gained from this project to reduce fracture risk, improve physical and functional ability, quality of life and ultimately survival rate in this population. A Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer; ACTRN12609000200280

  6. Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hamstra, Daniel A., E-mail: Daniel.Hamstra@gmail.com [Texas Oncology, Texas Center for Proton Therapy, Irving, Texas (United States); Mariados, Neil [Associated Medical Professionals of NY, PLLC, Syracuse, New York (United States); Sylvester, John [21st Century Oncology, Inc, Lakewood Ranch, East Bradenton, Florida (United States); Shah, Dhiren [Western New York Urology Associates, LLC, Doing Business as Cancer Care of WNY, Cheektowaga, New York (United States); Karsh, Lawrence [The Urology Center of Colorado, Denver, Colorado (United States); Hudes, Richard [Chesapeake Urology Associates, Doing Business as Chesapeake Urology Research Associates (The Prostate Center), Owings Mills, Maryland (United States); Beyer, David [Arizona Oncology Services Foundation, Phoenix, Arizona (United States); Kurtzman, Steven [Urological Surgeons of Northern California Inc, Campbell, California (United States); Bogart, Jeffrey [The Research Foundation of State University of New York/State University of New York Upstate Medical University, Syracuse, New York (United States); Hsi, R. Alex [Peninsula Cancer Center, Poulsbo, Washington (United States); Kos, Michael [Urology Nevada, Reno, Nevada (United States); Ellis, Rodney [University Hospitals Case Medical Center, Cleveland, Ohio (United States); Logsdon, Mark [Sutter Health Sacramento Sierra Region, Doing Business as Sutter Institute for Medical Research, Sacramento, California (United States); Zimberg, Shawn [Advanced Radiation Centers of New York, Lake Success, New York (United States); Forsythe, Kevin [Oregon Urology Institute, Springfield, Oregon (United States); Zhang, Hong [University of Rochester, Rochester, New York (United States); Soffen, Edward [CentraState Medical Center, Freehold, New Jersey (United States); Francke, Patrick [Carolina Regional Cancer Center, LLC, 21st Century Oncology, Inc, Myrtle Beach, South Carolina (United States); Mantz, Constantine [21st Century Oncology, Inc, Fort Meyers, Florida (United States); and others

    2017-04-01

    Purpose: SpaceOAR, a Food and Drug Administration–approved hydrogel intended to create a rectal–prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. Methods and Materials: Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. Results: The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02). Conclusions: The benefit of a hydrogel spacer in

  7. Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA).

    Science.gov (United States)

    Nguyen, Quan Dong; Merrill, Pauline T; Clark, W Lloyd; Banker, Alay S; Fardeau, Christine; Franco, Pablo; LeHoang, Phuc; Ohno, Shigeaki; Rathinam, Sivakumar R; Thurau, Stephan; Abraham, Abu; Wilson, Laura; Yang, Yang; Shams, Naveed

    2016-11-01

    To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Intravitreal sirolimus 440 μg demonstrated a significant

  8. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE: the IEO phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M.; Baio, Silvia M.; Lombardo, Dario; Chinol, Marco; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta; Ferrari, Mahila E. [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Fazio, Nicola [European Institute of Oncology, Division of Medical Oncology, Milan (Italy); Iodice, Simona [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Bartolomei, Mirco [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); M. Bufalini Hospital, Division of Nuclear Medicine, Cesena, FC (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Unit of Radiometabolic Medicine, Meldola, FC (Italy)

    2011-12-15

    Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst{sub 2}), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of {sup 177}Lu-DOTATATE in multiple cycles. Fifty-one consecutive patients with unresectable/metastatic sst{sub 2}-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of {sup 177}Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. {sup 177}Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. (orig.)

  9. Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial

    International Nuclear Information System (INIS)

    Hamstra, Daniel A.; Mariados, Neil; Sylvester, John; Shah, Dhiren; Karsh, Lawrence; Hudes, Richard; Beyer, David; Kurtzman, Steven; Bogart, Jeffrey; Hsi, R. Alex; Kos, Michael; Ellis, Rodney; Logsdon, Mark; Zimberg, Shawn; Forsythe, Kevin; Zhang, Hong; Soffen, Edward; Francke, Patrick; Mantz, Constantine

    2017-01-01

    Purpose: SpaceOAR, a Food and Drug Administration–approved hydrogel intended to create a rectal–prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. Methods and Materials: Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds. Results: The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P<.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P<.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02). Conclusions: The benefit of a hydrogel spacer in

  10. Efficacy and tolerability of lodenafil carbonate for oral therapy of erectile dysfunction: a phase III clinical trial.

    Science.gov (United States)

    Glina, Sidney; Fonseca, Gilvan N; Bertero, Eduardo B; Damião, Ronaldo; Rocha, Luíz C A; Jardim, Carlos R F; Cairoli, Carlos E; Teloken, Cláudio; Torres, Luiz O; Faria, Geraldo E; da Silva, Marcelo B; Pagani, Eduardo

    2010-05-01

    This is a phase III, prospective, randomized, double-blind, placebo-controlled clinical trial on lodenafil carbonate (LC), a novel phosphodiesterase 5 inhibitor developed in Brazil. Expanding information on LC efficacy and safety. International Index of Erectile Function (IIEF) erectile domain, positive answers to the sexual encounter profile (SEP)-2 and SEP-3 questions and incidence of adverse events (AEs). A total of 350 men with erectile dysfunction (ED) of all degrees were randomized to placebo, LC 40 mg or LC 80 mg and followed for 4 weeks. They completed the IIEF and answered the SEP questions 2 and 3 after each intercourse without and with the use of LC. IIEF Erectile Domain scores without and with the use of medication were the following (mean [M] +/- standard deviation [SD]): placebo = 13.9 +/- 5.2 and 14.8 +/- 7.8; LC 40 mg = 13.6 +/- 5.3 and 18.6 +/- 8.0; LC 80 mg = 13.4 +/- 4.9 and 20.6 +/- 7.7 (analysis of variance [ANOVA] P < 0.01). Positive answers to SEP-2 without and with the use of medication were the following (M +/- SD): placebo = 55.3 +/- 43.2% and 52.1 +/- 41.4%; LC 40 mg = 46.4 +/- 44.3% and 63.5 +/- 42.0%; LC 80 mg = 50.2 +/- 40.9% and 80.8 +/- 32.3% (ANOVA P < 0.01). Positive answers to SEP-3 were the following: placebo = 20.2 +/- 32.3% and 29.7 +/- 38.1%; LC 40 mg = 19.6 +/- 34.3% and 50.8 +/- 44.4%; LC 80 mg = 20.8 +/- 33.2% and 66.0 +/- 39.3% (ANOVA P < 0.01). The patients with at least one AE were placebo = 28.7%, LC 40 mg = 40.9%, and LC 80 mg = 49.5%. AEs whose incidence was significantly higher with LC than with placebo included rhinitis, headache, flushing, visual disorder, and dizziness. LC showed a satisfactory efficacy-safety profile for oral therapy of ED.

  11. Greenland plateau jets

    Directory of Open Access Journals (Sweden)

    George William Kent Moore

    2013-08-01

    Full Text Available The high ice-covered topography of Greenland represents a significant barrier to atmospheric flow and, as a direct and indirect result, it plays a crucial role in the coupled climate system. The wind field over Greenland is important in diagnosing regional weather and climate, thereby providing information on the mass balance of the ice sheet as well as assisting in the interpretation of ice core data. Here, we identify a number of hitherto unrecognised features of the three-dimensional wind field over Greenland; including a 2500-km-long jet along the central ice sheet's western margin that extends from the surface into the middle-troposphere, as well as a similar but smaller scale and less intense feature along its eastern margin. We refer to these features as Greenland Plateau Jets. The jets are coupled to the downslope katabatic flow and we argue that they are maintained by the zonal temperature gradients associated with the strong temperature inversion over the central ice sheet. Their importance for Greenland's regional climate is discussed.

  12. The Systems Approach to Functional Job Analysis. Task Analysis of the Physician's Assistant: Volume II--Curriculum and Phase I Basic Core Courses and Volume III--Phases II and III--Clinical Clerkships and Assignments.

    Science.gov (United States)

    Wake Forest Univ., Winston Salem, NC. Bowman Gray School of Medicine.

    This publication contains a curriculum developed through functional job analyses for a 24-month physician's assistant training program. Phase 1 of the 3-phase program is a 6-month basic course program in clinical and bioscience principles and is required of all students regardless of their specialty interest. Phase 2 is a 6 to 10 month period of…

  13. A phase I study of postoperative concurrent radiotherapy and oral doxifluridine and leucovorin for II/III stage rectal cancer

    International Nuclear Information System (INIS)

    Jin Jing; Li Yexiong; Tang Yuan; Wang Weihu; Wang Shulian; Song Yongwen; Liu Yueping; Yu Zihao; Liu Xinfan

    2008-01-01

    Objective: A phase I study was conducted to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity (DLT) of chemotherapy of oral doxifluridine (5-dFUR) and leucovorin with concurrent standard radiotherapy(RT) as adjuvant treatment in patients with rectal cancer. Methods: Patients aged 18-75 years old, Kamofsky scored ≥70%, stage II/III rectal cancer after curative surgery were eligible. Total RT dose was delivered as DT 50 Gy in the fraction of 2.0 Gy per day for 5 weeks to the pelvic area. 5-dFUR was administered concurrently with radiotherapy in escalating doses, and oral leucovorin was administered in a fixed dose of 30 mg/(m 2 ·d), both 3 times daily, from the 1 st day of RT to the last day. The DLTs included grade 3 or grade 4 hematologic and nonhematologie toxicity. Results: From Aug. 2005 to Mar. 2007, 16 patients were enrolled at the following dose levels: 450 mg/(m 2 ·d) (3 patients), 550 mg/(m 2 ·d) (6 patients) and 650 mg/(m 2 ·d) (7 patients). Diarrhea, neutropenia and nausea/vomit were the most common side effects although all neutropenia was less grade 3. The DLT was observed in 1 patient at 550 mg/(m 2 ·d) (grade 4 diarrhea), but none in the following 3 patients at the same dose level. At 650 mg/(m 2 ·d) level, the first patient quitted the study due to a severe abdominal cramp pain in the 3rd week of RT. In the following 3 enrolled patients, one suffered grade 3 abdominal cramp pain, diarrhea, fatigue, nausea/vomit and grade 2 neutropenia and fever. Grade 3 diarrhea was also observed in all the additional 3 patients at 650 mg/(m 2 ·d) dose level. So the dose escalation was ended up to 650 mg/(m 2 ·d). Four of 16 patients didn't complete the scheduled concurrent chemoradiotherapy due to severe side effects, including 1 at 550 mg/(m 2 ·d) dose level, and 3 at 650 mg/(m 2 ·d). The DLTs were observed as grade 3/4 diarrhea, grade 3 abdominal cramp pain, fatigue and nausea/vomit. Conclusions: Diarrhea is the most common and

  14. Interfacial Area and Interfacial Transfer in Two-Phase Flow Systems (Volume III. Chapters 11-14)

    Energy Technology Data Exchange (ETDEWEB)

    Guo, T.; Park, J.; Kojasoy, G.

    2003-03-15

    Experiments were performed on horizontal air-water bubbly two-phase flow, axial flow, stratified wavy flow, and annular flow. Theoretical studies were also undertaken on interfacial parameters for a horizontal two-phase flow.

  15. SCOPE1: a randomised phase II/III multicentre clinical trial of definitive chemoradiation, with or without cetuximab, in carcinoma of the oesophagus

    International Nuclear Information System (INIS)

    Hurt, Christopher N; Nixon, Lisette S; Griffiths, Gareth O; Al-Mokhtar, Ruby; Gollins, Simon; Staffurth, John N; Phillips, Ceri J; Blazeby, Jane M; Crosby, Tom D

    2011-01-01

    Chemoradiotherapy is the standard of care for patients with oesophageal cancer unsuitable for surgery due to the presence of co-morbidity or extent of disease, and is a standard treatment option for patients with squamous cell carcinoma of the oesophagus. Modern regimens of chemoradiotherapy can lead to significant long-term survival. However the majority of patients will die of their disease, most commonly with local progression/recurrence of their tumours. Cetuximab may overcome one of the principal mechanisms of tumour radio-resistance, namely tumour repopulation, in patients treated with chemoradiotherapy. The purpose of this research is first to determine whether the addition of cetuximab to definitive chemoradiotherapy for treatment of patients with non-metastatic carcinoma of the oesophagus is active (in terms of failure-free rate), safe, and feasible within the context of a multi-centre randomised controlled trial in the UK. If the first stage is successful then the trial will continue to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival. SCOPE1 is a two arm, open, randomised multicentre Phase II/III trial. Eligible patients will have histologically confirmed carcinoma of the oesophagus and have been chosen to receive definitive chemoradiotherapy by an accredited multidisciplinary team including a specialist Upper GI surgeon. 420 patients will be randomised to receive definitive chemoradiotherapy with or without cetuximab using a 1:1 allocation ratio. During Phase II of the study, the trial will assess safety (toxicity), activity (failure-free rate) and feasibility (recruitment rate and protocol dose modifications/delays) in 90 patients in the experimental arm. If the experimental arm is found to be active, safe, and feasible by the Independent Data Monitoring Committee then recruitment will continue into Phase III. This second stage will recruit a further 120 patients into each arm

  16. SCOPE1: a randomised phase II/III multicentre clinical trial of definitive chemoradiation, with or without cetuximab, in carcinoma of the oesophagus

    Directory of Open Access Journals (Sweden)

    Staffurth John N

    2011-10-01

    Full Text Available Abstract Background Chemoradiotherapy is the standard of care for patients with oesophageal cancer unsuitable for surgery due to the presence of co-morbidity or extent of disease, and is a standard treatment option for patients with squamous cell carcinoma of the oesophagus. Modern regimens of chemoradiotherapy can lead to significant long-term survival. However the majority of patients will die of their disease, most commonly with local progression/recurrence of their tumours. Cetuximab may overcome one of the principal mechanisms of tumour radio-resistance, namely tumour repopulation, in patients treated with chemoradiotherapy. The purpose of this research is first to determine whether the addition of cetuximab to definitive chemoradiotherapy for treatment of patients with non-metastatic carcinoma of the oesophagus is active (in terms of failure-free rate, safe, and feasible within the context of a multi-centre randomised controlled trial in the UK. If the first stage is successful then the trial will continue to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival. Methods/Design SCOPE1 is a two arm, open, randomised multicentre Phase II/III trial. Eligible patients will have histologically confirmed carcinoma of the oesophagus and have been chosen to receive definitive chemoradiotherapy by an accredited multidisciplinary team including a specialist Upper GI surgeon. 420 patients will be randomised to receive definitive chemoradiotherapy with or without cetuximab using a 1:1 allocation ratio. During Phase II of the study, the trial will assess safety (toxicity, activity (failure-free rate and feasibility (recruitment rate and protocol dose modifications/delays in 90 patients in the experimental arm. If the experimental arm is found to be active, safe, and feasible by the Independent Data Monitoring Committee then recruitment will continue into Phase III. This second

  17. A novel solid phase extraction procedure on Amberlite XAD-1180 for speciation of Cr(III), Cr(VI) and total chromium in environmental and pharmaceutical samples

    International Nuclear Information System (INIS)

    Narin, Ibrahim; Kars, Ayse; Soylak, Mustafa

    2008-01-01

    Due to the toxicity of chromium, species depend on their chemical properties and bioavailabilities, speciation of chromium is very important in environmental samples. A speciation procedure for chromium(III), chromium(VI) and total chromium in environmental samples is presented in this work, prior to flame atomic absorption spectrometric determination of chromium. The procedure is based on the adsorption of Cr(III)-diphenylcarbazone complex on Amberlite XAD-1180 resin. After oxidation of Cr(III), the developed solid phase extraction system was applied to determinate the total chromium. Cr(III) was calculated as the difference between the total Cr content and the Cr(VI) content. The analytical conditions for the quantitative recoveries of Cr(VI) on Amberlite XAD-1180 resin were investigated. The effects of some alkaline, earth alkaline, metal ions and also some anions were also examined. Preconcentration factor was found to be 75. The detection limits (LOD) based on three times sigma of the blank (N: 21) for Cr(VI) and total chromium were 7.7 and 8.6 μg/L, respectively. Satisfactory results for the analysis of total chromium in the stream sediment (GBW7310) certified reference material for the validation of the presented method was obtained. The procedure was applied to food, water and pharmaceutical samples successfully

  18. Phase-coherent transport and spin-orbit-coupling in III/V-semiconductor nanowires; Phasenkohaerenter Transport und Spin-Bahn-Wechselwirkung in III/V-Halbleiternanodraehten

    Energy Technology Data Exchange (ETDEWEB)

    Estevez Hernandez, Sergio

    2009-10-16

    Semiconductor nanowires fabricated by a bottom-up approach are not only interesting for the realization of future nanoscaled devices but also appear to be very attractive model systems to tackle fundamental questions concerning the transport in strongly confined systems. In order to avoid the problem connected with carrier depletion, narrowband gap semiconductors, i.e., InAs or InN, or core-shell Nanowires, i.e., GaAs/AlGaAs, are preferred. The underlying reason is that in InAs or InN the Fermi-level pinning in the conduction band results in a carrier accumulation at the surface. In fact, the tubular topology of the surface electron gas opens up the possibility to observe unconventional quantum transport phenomena. When the phase-coherence length in the nanowire is comparable to its dimensions the conductance fluctuates if a magnetic field is applied or if the electron concentration is changed by means of a gate electrode. These so-called universal conductance fluctuations being in the order of e{sup 2}/h originate from the fact that in small disordered samples, electron interference effects are not averaged out. In this work are analyzed universal conductance fluctuations to study the quantum transport properties in InN, InAs and GaAs/AlGaAs nanowires. With the use of a magnetic field and a back-gate electrode the universal conductance fluctuations and localizations effects were analyzed. Since InN and InAs are narrow band gap semiconductors, one naturally expects spin-orbit coupling effects. Because this phenomena is of importance for spin electronic applications. However, owing to the cylindrical symmetry of the InN and InAs nanowires, the latter effect was observable and actually be used to determine the strength of spin-orbit coupling. In order to clearly separate the weak antilocalization effect from the conductance fluctuations, the averaging of the magnetoconductance at different gate voltages was essential. The low-temperature quantum transport properties

  19. Postoperative opioid sparing with injectable hydroxypropyl-β-cyclodextrin-diclofenac: pooled analysis of data from two Phase III clinical trials

    Directory of Open Access Journals (Sweden)

    Gan TJ

    2016-12-01

    Full Text Available Tong J Gan,1 Neil Singla,2 Stephen E Daniels,3 Douglas A Hamilton,4,5 Peter G Lacouture,6,7 Christian RD Reyes,8 Daniel B Carr4,9 1Department of Anesthesiology, Stony Brook University, NY, 2Lotus Clinical Research, LLC, Pasadena, CA, 3Premier Research, Austin, TX, 4Javelin Pharmaceuticals, Inc., Cambridge, MA, 5New Biology Ventures, LLC, San Mateo, CA, 6Magidom Discovery, LLC, St Augustine, FL, 7Department of Emergency Medicine, Brown University School of Medicine, Providence, RI, 8Hospira Inc., Lake Forest, IL, 9Department of Anesthesiology, Tufts Medical Center, Boston, MA, USA Purpose: Use of nonopioid analgesics (including nonsteroidal anti-inflammatory drugs for postoperative pain management can reduce opioid consumption and potentially prevent opioid-related adverse events. This study examined the postoperative opioid-sparing effect of repeated-dose injectable diclofenac formulated with hydroxypropyl-β-cyclodextrin (HPβCD-diclofenac. Patients and methods: Pooled data from two double-blind, randomized, placebo- and active comparator-controlled Phase III trials were analyzed. Patients received HPβCD-diclofenac, placebo, or ketorolac by intravenous injection every 6 hours for up to 5 days following abdominal/pelvic or orthopedic surgery. Rescue opioid use was evaluated from the time of first study drug administration to up to 120 hours following the first dose in the overall study population and in subgroups defined by baseline pain severity, age, and HPβCD-diclofenac dose. Results: Overall, 608 patients received ≥1 dose of study medication and were included in the analysis. While 93.2% of patients receiving placebo required opioids, the proportion of patients requiring opioids was significantly lower for patients receiving HPβCD-diclofenac (18.75, 37.5, or 50 mg or ketorolac (P<0.005 for all comparisons. Mean cumulative opioid dose and number of doses were significantly lower among patients receiving HPβCD-diclofenac versus placebo

  20. The PACOVAR-trial: A phase I/II study of pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant recurrent, pre-treated ovarian cancer

    International Nuclear Information System (INIS)

    Eichbaum, Michael; Fersis, Nikos; Schmidt, Marcus; Wallwiener, Markus; Schneeweiss, Andreas; Sohn, Christof; Mayer, Christine; Eickhoff, Regina; Bischofs, Esther; Gebauer, Gerhard; Fehm, Tanja; Lenz, Florian; Fricke, Hans-Christian; Solomayer, Erich

    2011-01-01

    The prognosis of patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC) is poor. There is no standard treatment available. Emerging evidence suggests a major role for antiangiogenic treatment modalities in EOC, in particular in combination with the metronomic application of low dose chemotherapy. The novel, investigational oral antiangiogenic agent pazopanib targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit is currently being studied in different tumour types and is already used as first line therapy in recurrent renal cell carcinoma. A combined therapy consisting of pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, pretreated EOC. This study is designed as a multicenter phase I/II trial evaluating the optimal dose for pazopanib (phase I) as well as activity and tolerability of a combination regimen consisting of pazopanib and metronomic cyclophosphamide in the palliative treatment of patients with recurrent, platinum-resistant, pre-treated ovarian cancer (phase II). The patient population includes patients with histologically or cytologically confirmed diagnosis of EOC, cancer of the fallopian tube or peritoneal cancer which is platinumresistant or -refractory. Patients must have measurable disease according to RECIST criteria and must have failed available standard chemotherapy. Primary objectives are determination of the optimal doses for pazopanib (phase I) and the overall response rate according to RECIST criteria (phase II). Secondary objectives are time to progression, overall survival, safety and tolerability. The treatment duration is until disease progression or intolerability of study drug regimen (with a maximum of 13 cycles up to 52 weeks per subject). The current phase I/II trial shall clarify the potential of the multitargeting antiangiogenic tyrosinkinaseinhibitor GW 786034 (pazopanib) in

  1. Room temperature ionic liquids enhanced the speciation of Cr(VI) and Cr(III) by hollow fiber liquid phase microextraction combined with flame atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Zeng, Chujie; Lin, Yao; Zhou, Neng; Zheng, Jiaoting; Zhang, Wei

    2012-01-01

    Highlights: ► First reported enhancement effect of RTILs in HF-LPME for the speciation of chromium. ► The addition of RTILs led to 3.5 times improvement of the sensitivity of Cr(VI). ► The proposed method is a simplicity, sensitivity, low cost, green method. - Abstract: A new method for the speciation of Cr(VI) and Cr(III) based on enhancement effect of room temperature ionic liquids (RTILs) for hollow fiber liquid phase microextraction (HF-LPME) combined with flame atomic absorption spectrometry (FAAS) was developed. Room temperature ionic liquids (RTILs) and diethyldithiocarbamate (DDTC) were used enhancement reagents and chelating reagent, respectively. The addition of room temperature ionic liquids led to 3.5 times improvement in the determination of Cr(VI). In this method, Cr(VI) reacts with DDTC yielding a hydrophobic complex, which is subsequently extracted into the lumen of hollow fiber, whereas Cr(III) is remained in aqueous solutions. The extraction organic phase was injected into FAAS for the determination of Cr(VI). Total Cr concentration was determined after oxidizing Cr(III) to Cr(VI) in the presence of KMnO 4 and using the extraction procedure mentioned above. Cr(III) was calculated by subtracting of Cr(VI) from the total Cr. Under optimized conditions, a detection limit of 0.7 ng mL −1 and an enrichment factor of 175 were achieved. The relative standard deviation (RSD) was 4.9% for Cr(VI) (40 ng mL −1 , n = 5). The proposed method was successfully applied to the speciation of chromium in natural water samples with satisfactory results.

  2. Room temperature ionic liquids enhanced the speciation of Cr(VI) and Cr(III) by hollow fiber liquid phase microextraction combined with flame atomic absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Chujie, E-mail: cjzeng@126.com [Department of Chemistry and Material, Yulin Normal College, Yulin, Guangxi 537000 (China); Lin, Yao; Zhou, Neng; Zheng, Jiaoting; Zhang, Wei [Department of Chemistry and Material, Yulin Normal College, Yulin, Guangxi 537000 (China)

    2012-10-30

    Highlights: Black-Right-Pointing-Pointer First reported enhancement effect of RTILs in HF-LPME for the speciation of chromium. Black-Right-Pointing-Pointer The addition of RTILs led to 3.5 times improvement of the sensitivity of Cr(VI). Black-Right-Pointing-Pointer The proposed method is a simplicity, sensitivity, low cost, green method. - Abstract: A new method for the speciation of Cr(VI) and Cr(III) based on enhancement effect of room temperature ionic liquids (RTILs) for hollow fiber liquid phase microextraction (HF-LPME) combined with flame atomic absorption spectrometry (FAAS) was developed. Room temperature ionic liquids (RTILs) and diethyldithiocarbamate (DDTC) were used enhancement reagents and chelating reagent, respectively. The addition of room temperature ionic liquids led to 3.5 times improvement in the determination of Cr(VI). In this method, Cr(VI) reacts with DDTC yielding a hydrophobic complex, which is subsequently extracted into the lumen of hollow fiber, whereas Cr(III) is remained in aqueous solutions. The extraction organic phase was injected into FAAS for the determination of Cr(VI). Total Cr concentration was determined after oxidizing Cr(III) to Cr(VI) in the presence of KMnO{sub 4} and using the extraction procedure mentioned above. Cr(III) was calculated by subtracting of Cr(VI) from the total Cr. Under optimized conditions, a detection limit of 0.7 ng mL{sup -1} and an enrichment factor of 175 were achieved. The relative standard deviation (RSD) was 4.9% for Cr(VI) (40 ng mL{sup -1}, n = 5). The proposed method was successfully applied to the speciation of chromium in natural water samples with satisfactory results.

  3. Adsorption of As(III), As(V) and Cu(II) on zirconium oxide immobilized alginate beads in aqueous phase.

    Science.gov (United States)

    Kwon, Oh-Hun; Kim, Jong-Oh; Cho, Dong-Wan; Kumar, Rahul; Baek, Seung Han; Kurade, Mayur B; Jeon, Byong-Hun

    2016-10-01

    A composite adsorbent to remove arsenite [As(III)], arsenate [As(V)], and copper [Cu(II)] from aqueous phase was synthesized by immobilizing zirconium oxide on alginate beads (ZOAB). The composition (wt%) of ZOAB (Zr-34.0; O-32.7; C-21.3; Ca-1.0) was confirmed by energy dispersive X-ray (EDX) analysis. Sorption studies were conducted on single and binary sorbate systems, and the effects of contact time, initial adsorbate concentration, and pH on the adsorption performance of ZOAB (pHPZC = 4.3) were monitored. The sorption process for As(III)/As(V) and Cu(II) reached an equilibrium state within 240 h and 24 h, respectively, with maximum sorption capacities of 32.3, 28.5, and 69.9 mg g(-1), respectively. The addition of Cu(II) was favorable for As(V) sorption in contrast to As(III). In the presence of 48.6 mg L(-1) Cu(II), the sorption capacity of As(V) increased from 1.5 to 3.8 mg g(-1) after 240 h. The sorption data for As(III)/As(V) and Cu(II) conformed the Freundlich and Langmuir isotherm models, respectively. The adsorption of As(III), As(V), and Cu(II) followed pseudo second order kinetics. The effect of arsenic species on Cu(II) sorption was insignificant. The results of present study demonstrated that the synthesized sorbent could be useful for the simultaneous removal of both anionic and cationic contaminants from wastewaters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Magnetic solid-phase extraction combined with graphite furnace atomic absorption spectrometry for speciation of Cr(III) and Cr(VI) in environmental waters.

    Science.gov (United States)

    Jiang, Hong-mei; Yang, Ting; Wang, Yan-hong; Lian, Hong-zhen; Hu, Xin

    2013-11-15

    A new approach of magnetic solid phase extraction (MSPE) coupled with graphite furnace atomic absorption spectrometry (GFAAS) has been developed for the speciation of Cr(III) and Cr(VI) using zincon-immobilized silica-coated magnetic Fe3O4 nanoparticles (Zincon-Si-MNPs) as the MSPE absorbent. Cr(III) was quantitatively reserved on the absorbent at pH 9.1 while total Cr was reserved at pH 6.5. The absorbed Cr species were eluted by using 2 mol/L HCl and detected by GFAAS. The concentration of Cr(VI) could be calculated by subtracting Cr(III) from total Cr. All the parameters affecting the separation and extraction efficiency of Cr species such as pH, extraction time, concentration and volume of eluent, sample volume and influence of co-existing ions were systematically examined and the optimized conditions were established accordingly. The detection limit (LOD) of the method was 0.016 and 0.011 ng mL(-1) for Cr(III) and Cr(VI), respectively, with the enrichment factor of 100 and 150. The precisions of this method (Relative standard deviation, RSD, n=7) for Cr(III) and Cr(VI) at 0.1 ng mL(-1) were 6.0% and 6.2%, respectively. In order to validate the proposed method, a certified reference material of environmental water was analyzed, and the result of Cr speciation was in good agreement with the certified value. This MSPE-GFAAS method has been successfully applied for the speciation of Cr(III) and Cr(VI) in lake and tap waters with the recoveries of 88-109% for the spiked samples. Moreover, the MSPE separation mechanism of Cr(III) and Cr(VI) based on their adsorption-desorption on Zincon-Si-MNPs has been explained through various spectroscopic characterization. © 2013 Elsevier B.V. All rights reserved.

  5. Obtaining valid laboratory data in clinical trials conducted in resource diverse settings: lessons learned from a microbicide phase III clinical trial.

    Directory of Open Access Journals (Sweden)

    Tania Crucitti

    2010-10-01

    Full Text Available Over the last decade several phase III microbicides trials have been conducted in developing countries. However, laboratories in resource constrained settings do not always have the experience, infrastructure, and the capacity to deliver laboratory data meeting the high standards of clinical trials. This paper describes the design and outcomes of a laboratory quality assurance program which was implemented during a phase III clinical trial evaluating the efficacy of the candidate microbicide Cellulose Sulfate 6% (CS [1].In order to assess the effectiveness of CS for HIV and STI prevention, a phase III clinical trial was conducted in 5 sites: 3 in Africa and 2 in India. The trial sponsor identified an International Central Reference Laboratory (ICRL, responsible for the design and management of a quality assurance program, which would guarantee the reliability of laboratory data. The ICRL provided advice on the tests, assessed local laboratories, organized trainings, conducted supervision visits, performed re-tests, and prepared control panels. Local laboratories were provided with control panels for HIV rapid tests and Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG amplification technique. Aliquots from respective control panels were tested by local laboratories and were compared with results obtained at the ICRL.Overall, good results were observed. However, discordances between the ICRL and site laboratories were identified for HIV and CT/NG results. One particular site experienced difficulties with HIV rapid testing shortly after study initiation. At all sites, DNA contamination was identified as a cause of invalid CT/NG results. Both problems were timely detected and solved. Through immediate feedback, guidance and repeated training of laboratory staff, additional inaccuracies were prevented.Quality control guidelines when applied in field laboratories ensured the reliability and validity of final study data. It is essential that sponsors

  6. Alterations in the Rate of Limb Movement Using a Lower Body Positive Pressure Treadmill Do Not Influence Respiratory Rate or Phase III Ventilation

    OpenAIRE

    Michael J. Buono; Marissa Burnsed-Torres; Bethany Hess; Kristine Lopez; Catherine Ortiz; Ariel Girodo; Karen Lolli; Brett Bloom; David Bailey; Fred W. Kolkhorst

    2015-01-01

    The purpose of this study was to determine the effect of alterations in rate of limb movement on Phase III ventilation during exercise, independent of metabolic rate, gait style, and treadmill incline. Subjects completed five submaximal exercise bouts on a lower body positive pressure treadmill (AlterG P 200). The percent body weight for the five exercise bouts was 100, 87, 75, 63, and 50% and each was matched for carbon dioxide production (V CO2 ). Naturally, to match the V CO2 while reducin...

  7. Phase III Randomized Study of SB5, an Adalimumab Biosimilar, Versus Reference Adalimumab in Patients With Moderate‐to‐Severe Rheumatoid Arthritis

    OpenAIRE

    Weinblatt, Michael E.; Baranauskaite, Asta; Niebrzydowski, Jaroslaw; Dokoupilova, Eva; Zielinska, Agnieszka; Jaworski, Janusz; Racewicz, Artur; Pileckyte, Margarita; Jedrychowicz‐Rosiak, Krystyna; Cheong, Soo Yeon; Ghil, Jeehoon; Sokolovic, S.; Mekic, M.; Prodanovic, N.; Gajic, B.

    2017-01-01

    Objective SB5 is a biosimilar agent for adalimumab (ADA). The aim of this study was to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of SB5 in comparison with reference ADA in patients with rheumatoid arthritis (RA). Methods In this phase III, randomized, double‐blind, parallel‐group study, patients with moderately to severely active RA despite treatment with methotrexate were randomized 1:1 to receive SB5 or reference ADA at a dosage of 40 mg subcutaneously every o...

  8. Pre-Preliminary results from the phase III of the IAEA CRP: optimizing of reactor pressure vessel surveillance programmes and their analysis

    Energy Technology Data Exchange (ETDEWEB)

    Brumovsky, M; Gillemot, F; Kryukov, A; Levit, V

    1994-12-31

    This paper gives preliminary results and some conclusions from Phase III of the IAEA Coordinated Research Programme on ``Optimizing the Reactor Pressure Vessel Surveillance Programmes and their Analyses`` carried out during the last seven years in 15 member states. First analysis concerned: comparison of results from initial, un-irradiated materials condition, comparison of transition temperature shifts (from notch toughness testing) with respect to content of residual (P, Cu) and alloying (Ni) elements, type of material (base and weld metal), irradiation temperature (288 and 265 C), and type of fluence dependence. Special effort has been taken to the analysis of the behaviour of a chosen reference steel. (JRQ). 6 figs., 4 tabs.

  9. Parameters for calculation of nuclear reactions of relevance to non-energy nuclear applications (Reference Input Parameter Library: Phase III). Summary report of the first research coordination meeting

    International Nuclear Information System (INIS)

    Capote Noy, R.

    2004-08-01

    A summary is given of the First Research Coordination Meeting on Parameters for Calculation of Nuclear Reactions of Relevance to Non-Energy Nuclear Applications (Reference Input Parameter Library: Phase III), including a critical review of the RIPL-2 file. The new library should serve as input for theoretical calculations of nuclear reaction data at incident energies up to 200 MeV, as needed for energy and non-energy modern applications of nuclear data. Technical discussions and the resulting work plan of the Coordinated Research Programme are summarized, along with actions and deadlines. Participants' contributions to the RCM are also attached. (author)

  10. Solution and gas phase evidence of anion binding through the secondary bonding interactions of a bidentate bis-antimony(iii) anion receptor.

    Science.gov (United States)

    Qiu, J; Song, B; Li, X; Cozzolino, A F

    2017-12-20

    The solution and gas phase halide binding to a bis-antimony(iii) anion receptor was studied. This new class of anion receptors utilizes the strong Sb-centered secondary bonding interactions (SBIs) that are formed opposite to the polar Sb-O primary bond. 1 H NMR titration data were fitted statistically to binding models and solution-phase binding energetics were extracted, while the formation of anion-to-receptor complexes was observed using ESI-MS. Density functional theory calculations suggest that their affinity towards binding halide anions is mitigated by the strong explicit solvation effect in DMSO, which gives insights into future designs that circumvent direct solvent binding and are anticipated to yield tighter and perhaps more selectivity in anion binding.

  11. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

    Science.gov (United States)

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

    2016-02-01

    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

  12. Comprehensive analysis of published phase I/II clinical trials between 1990-2010 in osteosarcoma and Ewing sarcoma confirms limited outcomes and need for translational investment

    Directory of Open Access Journals (Sweden)

    van Maldegem Annemiek M

    2012-01-01

    Full Text Available Abstract Background High grade primary bone sarcomas are rare cancers that affect mostly children and young adults. Osteosarcoma and Ewing sarcoma are the most common histological subtypes in this age group, with current multimodality treatment strategies achieving 55-70% overall survival. As there remains an urgent need to develop new therapeutic interventions, we have reviewed published phase I/II trials that have been reported for osteosarcoma and Ewing sarcoma in the last twenty years. Results We conducted a literature search for clinical trials between 1990 and 2010, either for trials enrolling bone sarcoma patients as part of a general sarcoma indication or trials specifically in osteosarcoma and Ewing sarcoma. We identified 42 clinical trials that fulfilled our search criteria for general sarcoma that enrolled these patient groups, and eight and twenty specific trials for Ewing and osteosarcoma patients, respectively. For the phase I trials which enrolled different tumour types our results were incomplete, because the sarcoma patients were not mentioned in the PubMed abstract. A total of 3,736 sarcoma patients were included in these trials over this period, 1,114 for osteosarcoma and 1,263 for Ewing sarcoma. As a proportion of the worldwide disease burden over this period, these numbers reflect a very small percentage of the potential patient recruitment, approximately 0.6% for Ewing sarcoma and 0.2% for osteosarcoma. However, these data show an increase in recent activity overall and suggest there is still much room for improvement in the current trial development structures. Conclusion Lack of resources and commercial investment will inevitably limit opportunity to develop sufficiently rapid improvements in clinical outcomes. International collaboration exists in many well founded co-operative groups for phase III trials, but progress may be more effective if there were also more investment of molecular and translational research into

  13. 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

  14. Organizational restructuring and career plateauing

    NARCIS (Netherlands)

    P. Paffen; Hans Timmermans

    2009-01-01

    This article describes a flexibility program for plateaued professionals in a technical Dutch firm operating in the consultancy sector we will refer to with the pseudonym Greentree Corp. First, we will discuss the impact reorganization had on job-requirements and career opportunities for technical

  15. The structure of the blue luminescent delta-phase of tris(8-hydroxyquinoline)aluminium(III) (Alq3).

    Science.gov (United States)

    Cölle, Michael; Dinnebier, Robert E; Brütting, Wolfgang

    2002-12-07

    The existence of the facial isomer in the delta-phase of Alq3 is proven by X-ray structural analysis, revealing that both the different molecular structure and the weaker overlap of the pi-orbitals of hydroxyquinoline ligands belonging to neighboring Alq3 molecules as compared to other phases (alpha, beta) are likely to be the origin of the significantly different optical properties of delta-Alq3.

  16. Determination of As(III) and total inorganic As in water samples using an on-line solid phase extraction and flow injection hydride generation atomic absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Sigrist, Mirna, E-mail: msigrist@fiq.unl.edu.ar [Laboratorio Central, Facultad de Ingenieria Quimica, Universidad Nacional del Litoral, Santiago del Estero 2654-Piso 6, (3000) Santa Fe (Argentina); Albertengo, Antonela; Beldomenico, Horacio [Laboratorio Central, Facultad de Ingenieria Quimica, Universidad Nacional del Litoral, Santiago del Estero 2654-Piso 6, (3000) Santa Fe (Argentina); Tudino, Mabel [Laboratorio de Analisis de Trazas, Departamento de Quimica Inorganica, Analitica y Quimica Fisica/INQUIMAE, Facultad de Ciencias Exactas y Naturales, Pabellon II, Ciudad Universitaria (1428), Buenos Aires (Argentina)

    2011-04-15

    A simple and robust on-line sequential injection system based on solid phase extraction (SPE) coupled to a flow injection hydride generation atomic absorption spectrometer (FI-HGAAS) with a heated quartz tube atomizer (QTA) was developed and optimized for the determination of As(III) in groundwater without any kind of sample pretreatment. The method was based on the selective retention of inorganic As(V) that was carried out by passing the filtered original sample through a cartridge containing a chloride-form strong anion exchanger. Thus the most toxic form, inorganic As(III), was determined fast and directly by AsH{sub 3} generation using 3.5 mol L{sup -1} HCl as carrier solution and 0.35% (m/v) NaBH{sub 4} in 0.025% NaOH as the reductant. Since the uptake of As(V) should be interfered by several anions of natural occurrence in waters, the effect of Cl{sup -}, SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, HPO{sub 4}{sup 2-}, HCO{sub 3}{sup -} on retention was evaluated and discussed. The total soluble inorganic arsenic concentration was determined on aliquots of filtered samples acidified with concentrated HCl and pre-reduced with 5% KI-5% C{sub 6}H{sub 8}O{sub 6} solution. The concentration of As(V) was calculated by difference between the total soluble inorganic arsenic and As(III) concentrations. Detection limits (LODs) of 0.5 {mu}g L{sup -1} and 0.6 {mu}g L{sup -1} for As(III) and inorganic total As, respectively, were obtained for a 500 {mu}L sample volume. The obtained limits of detection allowed testing the water quality according to the national and international regulations. The analytical recovery for water samples spiked with As(III) ranged between 98% and 106%. The sampling throughput for As(III) determination was 60 samples h{sup -1}. The device for groundwater sampling was especially designed for the authors. Metallic components were avoided and the contact between the sample and the atmospheric oxygen was carried to a minimum. On-field arsenic species

  17. Determination of As(III) and total inorganic As in water samples using an on-line solid phase extraction and flow injection hydride generation atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Sigrist, Mirna; Albertengo, Antonela; Beldomenico, Horacio; Tudino, Mabel

    2011-01-01

    A simple and robust on-line sequential injection system based on solid phase extraction (SPE) coupled to a flow injection hydride generation atomic absorption spectrometer (FI-HGAAS) with a heated quartz tube atomizer (QTA) was developed and optimized for the determination of As(III) in groundwater without any kind of sample pretreatment. The method was based on the selective retention of inorganic As(V) that was carried out by passing the filtered original sample through a cartridge containing a chloride-form strong anion exchanger. Thus the most toxic form, inorganic As(III), was determined fast and directly by AsH 3 generation using 3.5 mol L -1 HCl as carrier solution and 0.35% (m/v) NaBH 4 in 0.025% NaOH as the reductant. Since the uptake of As(V) should be interfered by several anions of natural occurrence in waters, the effect of Cl - , SO 4 2- , NO 3 - , HPO 4 2- , HCO 3 - on retention was evaluated and discussed. The total soluble inorganic arsenic concentration was determined on aliquots of filtered samples acidified with concentrated HCl and pre-reduced with 5% KI-5% C 6 H 8 O 6 solution. The concentration of As(V) was calculated by difference between the total soluble inorganic arsenic and As(III) concentrations. Detection limits (LODs) of 0.5 μg L -1 and 0.6 μg L -1 for As(III) and inorganic total As, respectively, were obtained for a 500 μL sample volume. The obtained limits of detection allowed testing the water quality according to the national and international regulations. The analytical recovery for water samples spiked with As(III) ranged between 98% and 106%. The sampling throughput for As(III) determination was 60 samples h -1 . The device for groundwater sampling was especially designed for the authors. Metallic components were avoided and the contact between the sample and the atmospheric oxygen was carried to a minimum. On-field arsenic species separation was performed through the employ of a serial connection of membrane filters and

  18. Flow injection microfluidic device with on-line fluorescent derivatization for the determination of Cr(III) and Cr(VI) in water samples after solid phase extraction

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Guilong [Key Laboratory of Eco-Environment of Three Gorges Region of Ministry of Education, Chongqing University, Chongqing, 400045 (China); Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University, Beijing, 100084 (China); He, Qiang, E-mail: heqiang0980@163.com [Key Laboratory of Eco-Environment of Three Gorges Region of Ministry of Education, Chongqing University, Chongqing, 400045 (China); Lu, Ying [Department of Mathematics and Physics, Armed Police College, Chengdu, 610213 (China); Huang, Jing [Research Center for Advanced Computation, College of Science, Xihua University, Chengdu, 610039 (China); Lin, Jin-Ming, E-mail: jmlin@mail.tsinghua.edu.cn [Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University, Beijing, 100084 (China)

    2017-02-22

    In this paper, a rapid and simple method using magnetic multi-walled carbon nanotubes (MWCNTS), as a solid-phase extraction (SPE) sorbent, was successfully developed for extraction and preconcentration trace amounts of Cr(III) in water samples. The synthesized magnetic-MWCNTs nanocomposite was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). A rhodamine derivative (R1) was synthesized and characterized as a highly selective and sensitive fluorescent derivatizing agent for Cr(III). After SPE procedure, Cr(III) analysis was performed by flow injection microfluidic chip with on-line fluorescent derivatization and laser-induced fluorescence (LIF) spectroscopy detection. The parameters, which affected the efficiency of the developed method were investigated and optimized. Under the optimized conditions, the method exhibited a linear dynamic range of 0–10.0 nM, with a detection limit of 0.094 nM and an enrichment factor of 38. Furthermore, real water samples were analyzed and good recoveries were obtained from 91.0 to 101.6%. - Graphical abstract: Flow injection microfluidic device with on-line fluorescent derivatization and detection coupled to LIF. - Highlights: • A highly selective and sensitive derivatizing reagent for Cr(III) was synthesized and characterized. • The magnetic-MWCNTs nanocomposite as a SPE sorbent was successfully synthesized and characterized. • A new portable detection system was developed for microfluidic chip FIA platform.

  19. Alterations in the rate of limb movement using a lower body positive pressure treadmill do not influence respiratory rate or phase III ventilation.

    Science.gov (United States)

    Buono, Michael J; Burnsed-Torres, Marissa; Hess, Bethany; Lopez, Kristine; Ortiz, Catherine; Girodo, Ariel; Lolli, Karen; Bloom, Brett; Bailey, David; Kolkhorst, Fred W

    2015-01-01

    The purpose of this study was to determine the effect of alterations in rate of limb movement on Phase III ventilation during exercise, independent of metabolic rate, gait style, and treadmill incline. Subjects completed five submaximal exercise bouts on a lower body positive pressure treadmill (AlterG P 200). The percent body weight for the five exercise bouts was 100, 87, 75, 63, and 50% and each was matched for carbon dioxide production (V CO2 ). Naturally, to match the V CO2 while reducing the body weight up to 50% of normal required a significant increase in the treadmill speed from 3.0 ± 0.1 to 4.1 ± 0.2 mph, which resulted in a significant (P body weight) to 133 ± 6 at 4.1 mph (i.e., 50% of body weight). The most important finding was that significant increases in step frequency did not significantly alter minute ventilation or respiratory rate. Such results do not support an important role for the rate of limb movement in Phase III ventilation during submaximal exercise, when metabolic rate, gait style, and treadmill incline are controlled.

  20. Facilitating the implementation of the American College of Surgeons/Association of Program Directors in Surgery phase III skills curriculum: training faculty in the assessment of team skills.

    Science.gov (United States)

    Hull, Louise; Arora, Sonal; Stefanidis, Dimitrios; Sevdalis, Nick

    2015-11-01

    Effective teamwork is critical to safety in the operating room; however, implementation of phase III of the American College of Surgeons (ACS) and Association of Program Directors in Surgery (APDS) Curriculum that focuses on team-based skills remains worryingly low. Training and assessing the complexities of teamwork is challenging. The objective of this study was to establish guidelines and recommendations for training faculty in assessing/debriefing team skills. A multistage survey-based consensus study was completed by 108 experts responsible for training and assessing surgical residents from the ACS Accredited Educational Institutes. Experts agreed that a program to teach faculty to assess team-based skills should include training in the recognition of teamwork skills, practice rating these skills, and training in the provision of feedback/debriefing. Agreement was reached that faculty responsible for conducting team-based skills assessment should be revalidated every 2 years and stringent proficiency criteria should be met. Faculty development is critical to ensure high-quality, standardized training and assessment. Training faculty to assess team-based skills has the potential to facilitate the effective implementation of phase III of the ACS and APDS Curriculum. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Alterations in the Rate of Limb Movement Using a Lower Body Positive Pressure Treadmill Do Not Influence Respiratory Rate or Phase III Ventilation

    Directory of Open Access Journals (Sweden)

    Michael J. Buono

    2015-01-01

    Full Text Available The purpose of this study was to determine the effect of alterations in rate of limb movement on Phase III ventilation during exercise, independent of metabolic rate, gait style, and treadmill incline. Subjects completed five submaximal exercise bouts on a lower body positive pressure treadmill (AlterG P 200. The percent body weight for the five exercise bouts was 100, 87, 75, 63, and 50% and each was matched for carbon dioxide production (VCO2. Naturally, to match the VCO2 while reducing the body weight up to 50% of normal required a significant increase in the treadmill speed from 3.0±0.1 to 4.1±0.2 mph, which resulted in a significant (P<0.05 increase in the mean step frequency (steps per minute from 118±10 at 3 mph (i.e., 100% of body weight to 133±6 at 4.1 mph (i.e., 50% of body weight. The most important finding was that significant increases in step frequency did not significantly alter minute ventilation or respiratory rate. Such results do not support an important role for the rate of limb movement in Phase III ventilation during submaximal exercise, when metabolic rate, gait style, and treadmill incline are controlled.

  2. Clinical Signatures of Mucinous and Poorly Differentiated Subtypes of Colorectal Adenocarcinomas by a Propensity Score Analysis of an Independent Patient Database from Three Phase III Trials.

    Science.gov (United States)

    Kanda, Mitsuro; Oba, Koji; Aoyama, Toru; Kashiwabara, Kosuke; Mayanagi, Shuhei; Maeda, Hiromichi; Honda, Michitaka; Hamada, Chikuma; Sadahiro, Sotaro; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

    2018-04-01

    Although colorectal cancer comprises several histological subtypes, the influences of histological subtypes on disease progression and treatment responses remain controversial. We sought to evaluate the prognostic relevance of mucinous and poorly differentiated histological subtypes of colorectal cancer by the propensity score weighting analysis of prospectively collected data from multi-institute phase III trials. Independent patient data analysis of a pooled database from 3 phase III trials was performed. An integrated database of 3 multicenter prospective clinical trials (the Japanese Foundation for Multidisciplinary Treatment of Cancer 7, 15, and 33) was the source of study data. Surgery alone or postoperative adjuvant chemotherapy was offered in patients with resectable colorectal cancer. To balance essential variables more strictly for the comparison analyses, propensity score weighting was conducted with the use of a multinomial logistic regression model. We evaluated the clinical signatures of mucinous and poorly differentiated subtypes with regard to postoperative survival, recurrence, and chemosensitivity. Of 5489 patients, 136 (2.5%) and 155 (2.8%) were pathologically diagnosed with poorly differentiated and mucinous subtypes. The poorly differentiated subtypes were associated with a poorer prognosis than the "others" group (HR, 1.69; 95% CI, 1.00-2.87; p = 0.051), particularly in the patient subgroup of adjuvant chemotherapy (HR, 2.16). Although the mucinous subtype had a marginal prognostic impact among patients with stage I to III colorectal cancer (HR, 1.33; 95% CI, 0.90-1.96), it was found to be an independent prognostic factor in the subpopulation of patients with stage II disease, being associated with a higher prevalence of peritoneal recurrence. The treatment regimens of postoperative chemotherapy are now somewhat outdated. Both mucinous and poorly differentiated subtypes have distinct clinical characteristics. Patients with the mucinous subtype

  3. Simultaneous determination of Cr(iii) and Cr(vi) using reversed-phased ion-pairing liquid chromatography with dynamic reaction cell inductively coupled plasma mass spectrometry

    Science.gov (United States)

    Wolf, R.E.; Morrison, J.M.; Goldhaber, M.B.

    2007-01-01

    A method for the simultaneous determination of Cr(iii) and Cr(vi) species in waters, soil leachates and synthetic bio-fluids is described. The method uses reversed-phase ion-pairing liquid chromatography to separate the chromium species and a dynamic reaction cell (DRC??) equipped ICP-MS for detection of chromium. Separation of the chromium species is carried out in less than 2 min. Cr(iii) is complexed with ethylenediaminetetraacetic acid (EDTA) prior to separation by mixing samples with the mobile phase containing 2.0 mM tetrabutylammonium hydroxide (TBAOH), 0.5 mM EDTA (dipotassium salt), and 5% (vol/vol) methanol, adjusted to pH 7.6. The interfering 40Ar 12C+ background peak at mass 52 was reduced by over four orders of magnitude to less than 200 cps by using 0.65 mL min-1 ammonia as a reaction gas and an RPq setting on the DRC of 0.75. Method detection limits (MDLs) of 0.09 ??g L-1 for Cr(iii) and 0.06 ??g L-1 for Cr(vi) were obtained based on peak areas at mass 52 for 50 ??L injections of low level spikes. Reproducibility at 2 ??g L-1 was 3% RSD for 5 replicate injections. The tolerance of the method to various levels of common cations and anions found in natural waters and to matrix constituents found in soil leachates and simulated gastric and lung fluids was tested by performing spike recovery calculations for a variety of samples. ?? The Royal Society of Chemistry.

  4. 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...

  5. Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin.

    Science.gov (United States)

    Overman, Michael J; Morris, Van; Moinova, Helen; Manyam, Ganiraju; Ensor, Joe; Lee, Michael S; Eng, Cathy; Kee, Bryan; Fogelman, David; Shroff, Rachna T; LaFramboise, Thomas; Mazard, Thibault; Feng, Tian; Hamilton, Stanley; Broom, Bradley; Lutterbaugh, James; Issa, Jean-Pierre; Markowitz, Sanford D; Kopetz, Scott

    2016-10-11

    Hypermethylation of promoter CpG islands (CIMP) has been strongly implicated in chemotherapy resistance and is implicated in the pathogenesis of a subset of colorectal cancers (CRCs) termed CIMP-high. This phase I/II study in CRC (phase II portion restricted to CIMP-high CRC), treated fluoropyrimidine/oxaliplatin refractory patients with azacitidine (75 mg/m2/day subcutaneously D1-5) and CAPOX (capecitibine and oxaliplatin) every three weeks. Twenty-six patients (pts) were enrolled in this study: 15 pts (12 treated at MTD) in phase I and 11 pts in phase II. No dose limiting toxicities were observed. A total of 14 pts were CIMP-high. No responses were seen. CIMP-high status did not correlate with efficacy endpoints [stable disease (SD) or progression-free survival (PFS)] or baseline vimentin methylation level. Changes in vimentin methylation over time did not correlate with efficacy outcomes. Baseline methylated vimentin correlated with tumor volume (PCIMP-high pts, but no objective responses. Serum methylated vimentin may be associated with benefit from a regimen including a hypomethylation agent, although this study is not able to separate a potential prognostic or predictive role for the biomarker.

  6. Santé de l'écosystème urbain à Katmandou, au Népal - phase III ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les deux phases antérieures de ce projet (nos 003320 et 101277) ont permis la création et le renforcement de 18 groupes locaux ainsi que l'élaboration d'une nouvelle loi sur ... Assistance in synthesis and documentation of health, environment and development outcomes in urban eco-health project, Katmandu : report.

  7. "Brief Report: Increase in Production of Spoken Words in Some Children with Autism after PECS Teaching to Phase III"

    Science.gov (United States)

    Carr, Deborah; Felce, Janet

    2007-01-01

    The context for this work was an evaluation study [Carr, D., & Felce, J. A. (in press)] of the early phases of the Picture Exchange Communication System (PECS) [Frost, L. A., & Bondy, A. S. (1994). "The picture exchange communication system training manual." Cherry Hill, NJ: Pyramid Educational Consultants, Inc.; Frost, L. A., & Bondy, A. S.…

  8. Surface decoration of amine-rich carbon nitride with iron nanoparticles for arsenite (As{sup III}) uptake: The evolution of the Fe-phases under ambient conditions

    Energy Technology Data Exchange (ETDEWEB)

    Georgiou, Y., E-mail: yiannisgeorgiou@hotmail.com [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Mouzourakis, E., E-mail: emouzou@cc.uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Bourlinos, A.B., E-mail: bourlino@cc.uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Regional Centre of Advanced Technologies and Materials, Faculty of Science, Department of Physical Chemistry and Experimental Physics, Palacky University in Olomouc, 77146 (Czech Republic); Zboril, R., E-mail: radek.zboril@upol.cz [Regional Centre of Advanced Technologies and Materials, Faculty of Science, Department of Physical Chemistry and Experimental Physics, Palacky University in Olomouc, 77146 (Czech Republic); Karakassides, M.A., E-mail: mkarakas@cc.uoi.gr [Department of Materials Science and Engineering, University of Ioannina, Ioannina 45110 (Greece); Douvalis, A.P., E-mail: adouval@uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Bakas, Th., E-mail: tbakas@cc.uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Deligiannakis, Y., E-mail: ideligia@cc.uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece)

    2016-07-15

    Highlights: • Novel hybrid based on carbon nitride and iron nanoparticles (gC{sub 3}N{sub 4}-rFe). • gC{sub 3}N{sub 4}-rFe superior As{sup III} sorbent(76.5 mg g{sup −1}). • Surface complexation modeling of As{sup III} adsorption. • Dual mode EPR,monitoring of Fe{sup 2+} and Fe{sup 3+} evolution. - Abstract: A novel hybrid material (gC{sub 3}N{sub 4}-rFe) consisting of amine-rich graphitic carbon nitride (gC{sub 3}N{sub 4}), decorated with reduced iron nanoparticles (rFe) is presented. XRD and TEM show that gC{sub 3}N{sub 4}-rFe bears aggregation-free Fe-nanoparticles (10 nm) uniformly dispersed over the gC{sub 3}N{sub 4} surface. In contrast, non-supported iron nanoparticles are strongly aggregated, with non-uniform size distribution (20–100 nm). {sup 57}Fe-Mössbauer spectroscopy, dual-mode electron paramagnetic resonance (EPR) and magnetization measurements, allow a detailed mapping of the evolution of the Fe-phases after exposure to ambient O{sub 2}. The as-prepared gC{sub 3}N{sub 4}-rFe bears Fe{sup 2+} and Fe° phases, however only after long exposure to ambient O{sub 2}, a Fe-oxide layer is formed around the Fe° core. In this [Fe°/Fe-oxide] core-shell configuration, the gC{sub 3}N{sub 4}-rFe hybrid shows enhanced As{sup III} uptake capacity of 76.5 mg g{sup −1}, i.e., ca 90% higher than the unmodified carbonaceous support, and 300% higher than the non-supported Fe-nanoparticles. gC{sub 3}N{sub 4}-rFe is a superior As{sup III} sorbent i.e., compared to its single counterparts or vs. graphite/graphite oxide or activated carbon analogues (11–36 mg g{sup −1}). The present results demonstrate that the gC{sub 3}N{sub 4} matrix is not simply a net that holds the particles, but rather an active component that determines particle formation dynamics and ultimately their redox profile, size and surface dispersion homogeneity.

  9. The Pajarito Plateau: A bibliography

    Science.gov (United States)

    Mathien, Frances Joan; Steen, Charlie R.; Allen, Craig D.

    1993-01-01

    This bibliography is the result of two initially independent projects. As the consulting archaeologist at Los Alamos National Laboratory (LANL), Charlie R. Steen collected entries at the suggestion of the staff of the Environmental Surveillance Group of the Health, Safety, and Environmental Division, HSE-8. The primary purpose was to aid the staff in evaluating cultural resources on LANL lands. In addition to works that related to the archaeology and history of the area, Steen included notations of a few books and articles in other fields such as geology and natural history. It was hoped that they also would be of value to other organizations and to students of past human activities on the Pajarito Plateau.At the same time, the National Park Service (NPS) was planning a major survey of Bandelier National Monument (BNM). As part of this plan, the author was asked to prepare a background document that described research previously carried out in the area, including an annotated bibliography. Although the survey would be limited to the park boundaries, the larger Pajarito Plateau is a more logical study area from physiographic, environmental, and cultural perspectives; hence the focus was on this larger region. Mathien (1986) also included some references to natural resources studies, particularly those initiated by NPS within Bandelier National Monument.Both bibliographies were made available to Colleen Olinger and Beverly Larson of the Health and Environmental Services Group at Los Alamos. They realized that while neither was complete, each included entries missing from the other. Larson suggested the two bibliographies be combined. (At this time, Craig Allen was studying the landscape of the Jemez Mountains [Allen 1984c, 1989]. His investigations included much detailed information on natural resource studies and were added in 1991 and 1992.)To limit the scope of their work, Steen and Mathien had chosen their parameter: the Pajarito Plateau. Geographically, the

  10. Violent flows in aqueous foams III: physical multi-phase model comparison with aqueous foam shock tube experiments

    Science.gov (United States)

    Redford, J. A.; Ghidaglia, J.-M.; Faure, S.

    2018-06-01

    Mitigation of blast waves in aqueous foams is a problem that has a strong dependence on multi-phase effects. Here, a simplified model is developed from the previous articles treating violent flows (D'Alesio et al. in Eur J Mech B Fluids 54:105-124, 2015; Faure and Ghidaglia in Eur J Mech B Fluids 30:341-359, 2011) to capture the essential phenomena. The key is to have two fluids with separate velocities to represent the liquid and gas phases. This allows for the interaction between the two phases, which may include terms for drag, heat transfer, mass transfer due to phase change, added mass effects, to be included explicitly in the model. A good test for the proposed model is provided by two experimental data sets that use a specially designed shock tube. The first experiment has a test section filled with spray droplets, and the second has a range of aqueous foams in the test section. A substantial attenuation of the shock wave is seen in both cases, but a large difference is observed in the sound speeds. The droplets cause no observable change from the air sound speed, while the foams have a reduced sound speed of approximately 50-75 m/s . In the model given here, an added mass term is introduced in the governing equations to capture the low sound speed. The match between simulation and experiment is found to be satisfactory for both droplets and the foam. This is especially good when considering the complexity of the physics and the effects that are unaccounted for, such as three-dimensionality and droplet atomisation. The resulting statistics illuminate the processes occurring in such flows.

  11. Santé de l'écosystème urbain à Katmandou, au Népal - phase III ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les deux phases antérieures de ce projet (nos 003320 et 101277) ont permis la création et le renforcement de 18 groupes locaux ainsi que l'élaboration d'une nouvelle loi sur l'abattage des animaux et l'inspection des viandes, des amendements à la loi sur l'inspection des aliments et à la loi sur l'enlèvement des ordures ...

  12. A comparison of liquid and solid culture for determining relapse and durable cure in phase III TB trials for new regimens.

    Science.gov (United States)

    Phillips, Patrick P J; Mendel, Carl M; Nunn, Andrew J; McHugh, Timothy D; Crook, Angela M; Hunt, Robert; Bateson, Anna; Gillespie, Stephen H

    2017-11-24

    Tuberculosis kills more people than any other infectious disease, and new regimens are essential. The primary endpoint for confirmatory phase III trials for new regimens is a composite outcome that includes bacteriological treatment failure and relapse. Culture methodology is critical to the primary trial outcome. Patients in clinical trials can have positive cultures after treatment ends that may not necessarily indicate relapse, which was ascribed previously to laboratory cross-contamination or breakdown of old lesions. Löwenstein-Jensen (LJ) medium was the previous standard in clinical trials, but almost all current and future trials will use the Mycobacteria Growth Indicator Tube (MGIT) system due to its simplicity and consistency of use, which will affect phase III trial results. LJ was used for the definition of the primary endpoint in the REMoxTB trial, but every culture was also inoculated in parallel into the MGIT system. The data from this trial, therefore, provide a unique opportunity to investigate and compare the incidence of false 'isolated positives' in liquid and solid media and their potential impact on the primary efficacy results. All post-treatment positive cultures were reviewed in the REMoxTB clinical trial. Logistic regression models were used to model the incidence of isolated positive cultures on MGIT and LJ. A total of 12,209 sputum samples were available from 1652 patients; cultures were more often positive on MGIT than LJ. In 1322 patients with a favourable trial outcome, 126 (9.5%) had cultures that were positive in MGIT compared to 34 (2.6%) patients with positive cultures on LJ. Among patients with a favourable outcome, the incidence of isolated positives on MGIT differed by study laboratory (p cultures in some patients even after adjusting for laboratory, p cultures, positive MGIT cultures were more likely to be associated with higher grade TB symptoms reported within 7 days either side of sputum collection in patients with an

  13. Monuments of the Giza Plateau

    Science.gov (United States)

    Ruggles, Clive L. N.

    The colossal pyramids of the pharaohs Khufu (Cheops), Khafre (Chephren), and Menkaure (Mycerinus) have attracted a huge amount of astronomical interest over the years, both scholarly and popular. Less attention is usually given to the broader context of structures on the Giza Plateau. One of the most notorious ideas connecting the Giza Plateau with astronomy is that the three large pyramids are laid out on the ground so as to reflect the appearance of the three stars of Orion's Belt in the sky. This idea is unsupportable for several reasons but has succeeded in generating huge public interest. Of much greater serious interest is the fact that the three main pyramids were oriented cardinally to extraordinary precision, which raises the questions of why this was important and how it was achieved. Another idea that has attracted serious attention but also some confusion is that the orientations of some narrow shafts within Khufu's pyramid might have been deliberately aligned upon particular stars. The overall layout of monuments on the plateau may certainly have been designed so as to emphasize certain solar phenomena, for symbolic and ideological reasons relating to a dominant sun cult. It is also possible that it formed part of a wider cosmological "master plan" extending to other pyramids and temples up to 20 km distant.

  14. Microbial Mineral Transformations at the Fe(II)/Fe(III) Redox Boundary for Solid Phase Capture of Strontium and Other Metal/Radionuclide Contaminants

    International Nuclear Information System (INIS)

    Ferris, F.G.; Roden, E.E.

    2000-01-01

    The migration of 90 Sr in groundwater is a significant environmental concern at former nuclear weapons production sites in the US and abroad. Although retardation of 90 Sr transport relative to mean groundwater velocity is known to occur in contaminated aquifers, Sr 2+ does not sorb as strongly to iron oxides and other mineral phases as do other metal-radionuclides contaminants. Thus, some potential exists for extensive 90 Sr migration from sources of contamination. Chemical or biological processes capable of retarding or immobilizing Sr 2+ in groundwater environments are of interest from the standpoint of understanding controls on subsurface Sr 2+ migration. In addition, it may be possible to exploit such processes for remediation of subsurface Sr contamination. In this study the authors examined the potential for the solid phase sorption and incorporation of Sr 2+ into carbonate minerals formed during microbial Fe(III) oxide reduction as a first step toward evaluating whether this process could be used to promote retardation of 90 Sr migrations in anaerobic subsurface environments. The demonstration of Sr 2+ capture in carbonate mineral phases formed during bacterial HFO reduction and urea hydrolysis suggests that microbial carbonate mineral formation could contribute to Sr 2+ retardation in groundwater environments. This process may also provide a mechanism for subsurface remediation of Sr 2+ and other divalent metal contaminants that form insoluble carbonate precipitates

  15. Integrated Sensing & Controls for Coal Gasification - Development of Model-Based Controls for GE's Gasifier & Syngas Cooler. Topical Rerport for Phase III

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Aditya

    2011-02-17

    This Topical Report for the final Phase III of the program summarizes the results from the Task 3 of the program. In this task, the separately designed extended Kalman Filter (EKF) and model predictive controls (MPC) with ideal sensing, developed in Phase II, were integrated to achieve the overall sensing and control system for the gasification section of an IGCC plant. The EKF and MPC algorithms were updated and re-tuned to achieve closed-loop system stability as well as good steady-state and transient control response. In particular, the performance of the integrated EKF and MPC solution was tested extensively through multiple simulation studies to achieve improved steady-state as well as transient performance, with coal as well as coal-petcoke blended fuel, in the presence of unknown modeling errors as well as sensor errors (noise and bias). The simulation studies demonstrated significant improvements in steady state and transient operation performance, similar to that achieved by MPC with ideal sensors in Phase II of the program.

  16. A phase I/II exploratory clinical trial for intracordal injection of recombinant hepatocyte growth factor for vocal fold scar and sulcus.

    Science.gov (United States)

    Hirano, Shigeru; Kawamoto, Atsuhiko; Tateya, Ichiro; Mizuta, Masanobu; Kishimoto, Yo; Hiwatashi, Nao; Kawai, Yoshitaka; Tsuji, Takuya; Suzuki, Ryo; Kaneko, Mami; Naito, Yasushi; Kagimura, Tatsuo; Nakamura, Tatsuo; Kanemaru, Shin-Ichi

    2018-04-01

    Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 μg of HGF per vocal fold; Step II received 3 μg of HGF; and Step III received 10 μg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus. Copyright © 2017 John Wiley & Sons, Ltd.

  17. GILT - A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Flentje, Michael [University Hospital Wuerzburg, Dept. of Radiotherapy, Wuerzburg (Germany); Huber, Rudolf M. [University Hospital Munich, Member of the German Center for Lung Research (DZL CPC-M), Munich (Germany); Engel-Riedel, Walburga [University Hospital Merheim, Dept. of Pneumonology, Cologne (Germany); Andreas, Stefan [Dept. of Pneumonology, Immenhausen (Germany); Kollmeier, Jens [Helios Emil-von-Behring Hospital, Berlin (Germany); Staar, Susanne [Municipal Hospital Bremen-Mitte, Bremen (Germany); Dickgreber, Nicolas [University Hospital Hannover, Hannover (Germany); Vaissiere, Nathalie; Almeida, Cecilia de [Institut de Recherche Pierre Fabre, Boulogne (France); Edlich, Birgit [Pierre Fabre Pharma GmbH, Freiburg (Germany); Fietkau, Rainer [University Hospital Erlangen, Erlangen (Germany)

    2016-04-15

    Concurrent chemoradiotherapy (CRT) is considered standard for inoperable stage III non-small cell lung cancer (NSCLC). Consolidation chemotherapy (CC) following CRT is intended to further improve outcomes, yet studies have shown discordant results. This phase III study assessed CRT followed by best supportive care (BSC) or consolidation with oral vinorelbine and cisplatin. Patients received two cycles of oral vinorelbine (50 mg/m{sup 2} days 1, 8 and 15) + cisplatin (20 mg/m{sup 2} days 1-4) q4w + radiotherapy (RT; 66 Gy). Patients with at least stable disease (SD) were randomised to either two cycles oral vinorelbine (60-80 mg/m{sup 2} days 1 and 8) + cisplatin (80 mg/m{sup 2} day 1) q3w + BSC or BSC alone. Primary endpoint was progression-free survival (PFS). A total of 279 patients were enrolled for CRT and 201 patients were randomised to CC or BSC. Both CRT and CC were well tolerated, with limited radiation-mediated grade 3/4 toxicities (CRT/CC/BSC: oesophagitis-related events 12.9 %/3.1 %/0 %; grade 3 pneumonitis 0 %/0 %/2 %) and chemotherapy-mediated grade 3/4 toxicities (CRT/CC: neutropenia 11.2 %/22.1 %; leukopenia 18.3 %/26.7 %; grade 3 nausea 5.0 %/2.3 %, grade 3 vomiting 3.2 %/3.5 %). Median PFS from randomisation was 6.4 (5.0-8.7) and 5.5 (3.8-7.4) months in the CC and BSC arms (hazard ratio, HR = 0.93 [0.69-1.26]; p = 0.63), respectively; median overall survival (OS) 20.8 (13.5-25.3) and 18.5 (13.6-24.7) months, respectively. Consolidation chemotherapy after concurrent CRT did not prolong PFS or OS. Concurrent RT with oral vinorelbine and cisplatin demonstrated a favourable safety profile and represents a suitable treatment regimen for inoperable stage III NSCLC. (orig.) [German] Simultane Radiochemotherapie (CRT) wird als Standardtherapie beim inoperablen Stadium III des nicht-kleinzelligen Lungenkarzinoms (NSCLC) angesehen. Konsolidierende Chemotherapie (CC) nach der CRT zielt darauf ab, das Therapieergebnis zu verbessern, allerdings zeigen Studien

  18. Phase I-II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints.

    Science.gov (United States)

    Winqvist, Maria; Mozaffari, Fariba; Palma, Marzia; Eketorp Sylvan, Sandra; Hansson, Lotta; Mellstedt, Håkan; Österborg, Anders; Lundin, Jeanette

    2017-01-01

    This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3-4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67 + ) CD8 + T cells was increased at week 4, with further increase in both the CD4 + and CD8 + subsets (p cells increased at week 4 as the frequency of effector memory cells increased in the CD8 + subset (p cells decreased in both the CD8 + and CD4 + subsets (p regulatory T cells was reduced (p T cells decreased, and effector memory T cells increased (p T cells increased at 30-week follow-up (p T cells, including increased proliferative activity and cytotoxic potential.

  19. Novel corrosion experiments using the wire beam electrode: (III) Measuring electrochemical corrosion parameters from both the metallic and electrolytic phases

    International Nuclear Information System (INIS)

    Tan, Yong-Jun; Liu, Tie; Aung, Naing Naing

    2006-01-01

    The wire beam electrode (WBE) and the scanning reference electrode technique (SRET) have been applied in a novel combination to measure, for the first time, electrochemical parameters simultaneously from both the metallic and electrolytic phases of a corroding metal surface. The objective of this work is to demonstrate the application of this combined WBE-SRET method in obtaining unique information on localised corrosion mechanism, by investigating typical corrosion processes occurring over a mild steel WBE surface exposed to the classic Evans solution. The WBE method was used to map current and potential distributions in the metallic phase, and the SRET was used to map current or potential distribution in the electrolytic phase. It has been found that the combined WBE-SRET method is able to gain useful information on macro-cell electrochemical corrosion processes that involve macro-scale separation of anodes and cathodes. In such macro-cell corrosion systems, maps measured using WBE and SRET were found to correlate with each other and both methods were able to detect the locations of anodic sites. However the movement of the scanning probe during SRET measurements was found to affect the SRET detection of cathodic sites. In micro-cell corrosion systems where the separation of anodic and cathodic sites were less distinct, SRET measurement was found to be insensitive in detecting anodic and cathodic sites, while the WBE method was still able to produce results that correlated well with observed corrosion behaviour. Results obtained from this work suggest that the WBE-SRET method is applicable for understanding the initiation, propagation and electrochemical behaviour of localised corrosion anodes and cathodes, and also their dependence on externally controllable variables, such as solution pH changes and the existence of surface coatings

  20. On some derived compounds of fluorides of Cerium III or IV: defined compounds and non stoichiometric phases

    International Nuclear Information System (INIS)

    Besse, Jean-Pierre

    1968-01-01

    This research study addresses the study of rare earth fluorides. It reports the preparation and study of new fluoro-cerates (IV) in order to complete the set of already known compounds (ammonium fluoro-cerate, and alkaline earth compounds), the study of binary CeF 3 binary systems, monovalent and divalent fluorides, and CeF 3 -NF 2 -N'F ternary systems, and the study of non stoichiometric phases in CeF 3 oxides, sulphides and selenides [fr

  1. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations.

    LENUS (Irish Health Repository)

    Sequist, Lecia V

    2013-09-20

    The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR\\/ErbB1), human epidermal growth factor receptor 2 (HER2\\/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).

  2. Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.

    Science.gov (United States)

    Thomas, A L; Cox, G; Sharma, R A; Steward, W P; Shields, F; Jeyapalan, K; Muller, S; O'Byrne, K J

    2000-12-01

    The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.

  3. Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity

    International Nuclear Information System (INIS)

    Williams, Maureen S.; Burk, Mary; Loprinzi, Charles L.; Hill, Mary; Schomberg, Paula J.; Nearhood, Kim; O'Fallon, Judith R.; Laurie, John A.; Shanahan, Thomas G.; Moore, Randy L.; Urias, Rodolfo E.; Kuske, Robert R.; Engel, Roland E.; Eggleston, William D.

    1996-01-01

    Purpose: Considerable pilot data and clinical experience suggested that an aloe vera gel might help to prevent radiation therapy-induced dermatitis. Methods and Materials: Two Phase III randomized trials were conducted. The first one was double blinded, utilized a placebo gel, and involved 194 women receiving breast or chest wall irradiation. The second trial randomized 108 such patients to aloe vera gel vs. no treatment. Skin dermatitis was scored weekly during both trials both by patients and by health care providers. Results: Skin dermatitis scores were virtually identical on both treatment arms during both of the trials. The only toxicity from the gel was rare contact dermatitis. Conclusions: This dose and schedule of an aloe vera gel does not protect against radiation therapy-induced dermatitis

  4. 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)

  5. A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer

    International Nuclear Information System (INIS)

    Warde, Padraig; O'Sullivan, Brian; Aslanidis, Julie; Kroll, Barbaranne; Lockwood, Gina; Waldron, John; Payne, David; Bayley, Andrew; Ringash, Jolie; Kim, John; Liu, F.-F.; Maxymiw, Walter; Sprague, Shelley; Cummings, Bernard J.

    2002-01-01

    Purpose: To test the hypothesis that the use of oral pilocarpine during and after radiotherapy (RT) for head-and-neck cancer would reduce the symptoms of post-RT xerostomia. Methods and Materials: One hundred thirty patients were randomized in a double-blind method to receive either pilocarpine (5-mg tablets) or placebo three times daily starting on Day 1 of RT and continuing for 1 month after treatment. The eligibility criteria included a planned dose of >50 Gy as radical or postoperative RT for head-and-neck cancer, with at least 50% of both parotid glands included in the treatment fields. The primary outcome measure was the severity of xerostomia as assessed by a patient-completed linear analog scale 3 months after RT. Secondary outcome measures included quality of life during therapy (as assessed by the McMaster University Head-and-Neck Questionnaire) and severity of mucositis during RT (as assessed using Radiation Therapy Oncology Group scales). Results: No difference was observed between the pilocarpine-treated patients and the placebo group in the severity of xerostomia score as assessed by linear analog scale at baseline and 1, 3, and 6 months after treatment (repeated measures analysis, p=0.92). No difference was apparent in the severity of mucositis during RT; 56.3% of patients receiving pilocarpine had Grade III/IV mucositis compared with 50.8% treated with placebo. No difference in quality of life was noted between the treatment groups during or after RT. The questionnaire score at 3 months after RT was 5.0 (SD 1.0). in the pilocarpine group and 4.9 (SD 0.9) in the placebo group. Conclusion: We were unable to detect a beneficial effect of pilocarpine on RT-induced xerostomia when administered during RT for head-and-neck cancer

  6. A phase III multicenter trail of radiosensitizing effect and safety of sodium glycididazole in thoracic esophageal squamous carcinoma

    International Nuclear Information System (INIS)

    Qin Shangbin; Wang Yadi; Yang Junquan; Wang Xiaohu; Li Haibin; Yang Zhiyong; Yu Hong; Li Xueying; Gao Xianshu

    2012-01-01

    Objective: To evaluate the efficacy and clinical safety glycididazole (CMNa) in thoracic esophageal squamous carcinoma. Methods: From June 1, 2008 to October 13, 2009, 66 pathologically proved thoracic esophageal squamous carcinoma (stage II a -III, stage IV with metastases only in supraclavicular lymph nodes, by AJCC 6 th ed) were randomized into radiotherapy plus CMNa (A) or radiotherapy plus placebo (B) group. Radiotherapy was given by conventional schedule: 1.8-2.0 Gy per fraction, 5 times per week to a total dose of 66 Gy/6.6-7.2 w. CMNa was given intravenously 800 mg/m 2 3 times a week in solution of 100 ml saline within 30 minutes. Radiotherapy was started 30-60 minutes after completion of infusion. Patients of Group B received placebo in saline solution. A total of 66 patients were enrolled (Group A: 32; Group B: 34), and four patients were unanalyzable, remaining 31 patients in each Group. Baseline factors were balanced. Results: Follow-up rate was 97%. Group A vs. Group B: the overall response rate was 93.5% vs. 67.7% (χ 2 =6.61, P=0.01), 2-year overall survival was 39.9% vs. 29.9% (χ 2 = 0.62, P=0.433), 2-year cancer specific survival was 43.1% vs. 26.8% (χ 2 = 0.30, P=0.878), and 2-year progression-free survival was 30.1% vs. 27.9% (χ 2 = 0.02, P=0.586). No severe side effects observed. All patients tolerated CMNa infusion well. Conclusions: CMNa is tolerable and effective as a hypoxic radiosensitizer, and its combination with radiotherapy can improve short term effect. However, survival is not improved within our follow-up period. (authors)

  7. Pharmacokinetic monitoring and dose modification of etanidazole in the RTOG 85-27 phase III head and neck trial

    International Nuclear Information System (INIS)

    Riese, Nancy E.; Buswell, Lori; Noll, Lisa; Pajak, Thomas F.; Stetz, JoAnn; Lee, D.J.; Coleman, C. Norman

    1997-01-01

    Purpose: To prospectively evaluate the pharmacokinetic monitoring and drug dose adjustment of Etanidazole (Eta) in patients treated on the RTOG randomized trial for Stage III and IV head and neck cancer. Methods and Materials: From June, 1986 to October, 1991, 521 patients were randomized to conventional RT alone or RT plus Eta. The primary goal was to determine whether the addition of Eta to conventional radiation therapy improves local-regional control and tumor-free survival. Of the 264 patients who received Eta, 233 had their drug exposure calculated and the Eta dose and schedule adjusted accordingly to prevent the occurrence of serious peripheral neuropathy. Drug exposure was assessed using the area under the curve (AUC) for a single treatment that was calculated by the integral over time of the serum concentration of Eta. The total drug exposure (total-AUC) was estimated by multiplying the AUC by the number of drug administrations. Results: Eighteen percent of patients developed Grade I and 6% developed Grade II peripheral neuropathy. There was no Grade 3 or 4 peripheral neuropathy. There is a trend for an increased risk of neuropathy by single dose AUC. The minimal difference in incidence of neuropathy by single-dose AUC was due to the use of dose and schedule modification for patients with the higher values. Conclusions: The pharmacokinetics investigated in this study confirm previous work that monitoring Eta levels, with dose adjustment, allows it to be used safely in the clinic. In a subset analysis there was a statistically significant improvement in local-regional control and survival rates for patients with N0 and N1 disease, that will require confirmation (14). However, the clinical efficacy of Eta in this trial proved to be of little overall benefit

  8. Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine

    Directory of Open Access Journals (Sweden)

    Carter Terrell

    2011-08-01

    Full Text Available Abstract Background A pivotal phase III study of the RTS,S/AS01 malaria candidate vaccine is ongoing in several research centres across Africa. The development and establishment of quality systems was a requirement for trial conduct to meet international regulatory standards, as well as providing an important capacity strengthening opportunity for study centres. Methods Standardized laboratory methods and quality assurance processes were implemented at each of the study centres, facilitated by funding partners. Results A robust protocol for determination of parasite density based on actual blood cell counts was set up in accordance with World Health Organization recommendations. Automated equipment including haematology and biochemistry analyzers were put in place with standard methods for bedside testing of glycaemia, base excess and lactacidaemia. Facilities for X-rays and basic microbiology testing were also provided or upgraded alongside health care infrastructure in some centres. External quality assurance assessment of all major laboratory methods was established and method qualification by each laboratory demonstrated. The resulting capacity strengthening has ensured laboratory evaluations are conducted locally to the high standards required in clinical trials. Conclusion Major efforts by study centres, together with support from collaborating parties, have allowed standardized methods and robust quality assurance processes to be put in place for the phase III evaluation of the RTS, S/AS01 malaria candidate vaccine. Extensive training programmes, coupled with continuous commitment from research centre staff, have been the key elements behind the successful implementation of quality processes. It is expected these activities will culminate in healthcare benefits for the subjects and communities participating in these trials. Trial registration Clinicaltrials.gov NCT00866619

  9. Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

    Directory of Open Access Journals (Sweden)

    Smolich Beverly D

    2003-02-01

    Full Text Available Abstract Background Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Methods Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF receptor tyrosine kinase (RTK inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Results Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9 as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. Conclusions These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies.

  10. Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

    International Nuclear Information System (INIS)

    DePrimo, Samuel E; Wong, Lily M; Khatry, Deepak B; Nicholas, Susan L; Manning, William C; Smolich, Beverly D; O'Farrell, Anne-Marie; Cherrington, Julie M

    2003-01-01

    Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC) samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9) as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies

  11. The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

    International Nuclear Information System (INIS)

    Vuong, Te; Waschke, Kevin; Niazi, Tamim; Richard, Carole; Parent, Josee; Liberman, Sender; Mayrand, Serge; Loungnarath, Rasmy; Stein, Barry; Devic, Slobodan

    2011-01-01

    Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

  12. DAPPA grafted polymer: an efficient solid phase extractant for U(VI), Th(IV) and La(III) from acidic waste streams and environmental samples.

    Science.gov (United States)

    Raju, Ch Siva Kesava; Subramanian, M S

    2005-07-15

    A new class of polymeric resin has been synthesized by grafting Merrifield chloromethylated resin with (dimethyl amino-phosphono-methyl)-phosphonic acid (MCM-DAPPA), for the preconcentration of U(VI), Th(IV) and La(III) from both acidic wastes and environmental samples. The various chemical modification steps involved during grafting process are characterized by FT-IR spectroscopy, (31)P and (13)C-CPMAS (cross-polarized magic angle spin) NMR spectroscopy and CHNS/O elemental analysis. The water regain capacity data for the grafted polymer are obtained from thermo-gravimetric (TG) analysis. The influence of various physico-chemical parameters during the quantitative extraction of metal ions by the resin phase are studied and optimized by both static and dynamic methods. The significant feature of this grafted polymer is its ability to extract both actinides and lanthanides from high-level acidities as well as from near neutral conditions. The resin shows very high sorption capacity values of 2.02, 0.89 and 0.54mmolg(-1) for U(VI), 1.98, 0.63 and 0.42mmolg(-1) for Th(IV) and 1.22, 0.39 and 0.39mmolg(-1) for La(III) under optimum pH, HNO(3) and HCl concentration, respectively. The grafted polymer shows faster phase exchange kinetics (99.5% recovery using 1M (NH(4))(2)CO(3), as eluent. The developed grafted resin has been successfully applied in extracting Th(IV) from high matrix monazite sand, U(VI) from sea water and also U(VI) and Th(IV) from simulated nuclear spent fuel mixtures. The analytical data obtained from triplicate measurements are within 3.9% R.S.D. reflecting the reproducibility and reliability of the developed method.

  13. Clinical impact of tumor location on the colon cancer survival and recurrence: analyses of pooled data from three large phase III randomized clinical trials.

    Science.gov (United States)

    Aoyama, Toru; Kashiwabara, Kosuke; Oba, Koji; Honda, Michitaka; Sadahiro, Sotaro; Hamada, Chikuma; Maeda, Hiromichi; Mayanagi, Shuhei; Kanda, Mitsuro; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

    2017-11-01

    The aim of the present study was to determine whether or not the overall survival (OS) and disease-free survival (DFS) were affected by the tumor location in patients who underwent curative resection for colon cancer in a pooled analysis of three large phase III studies performed in Japan. In total, 4029 patients were included in the present study. Patients were classified as having right-side colon cancer (RC) if the primary tumor was located in the cecum, ascending colon, hepatic flexure or transverse colon, and left-side colon cancer (LCC) if the tumor site was within the splenic flexure, descending colon, sigmoid colon or recto sigmoid junction. The risk factors for the OS and DFS were analyzed. In the present study, 1449 patients were RC, and 2580 were LCC. The OS rates at 3 and 5 years after surgery were 87.6% and 81.6% in the RC group and 91.5% and 84.5% in the LCC group, respectively. Uni- and multivariate analyses showed that RRC increased the risk of death by 19.7% (adjusted hazard ratio = 1.197; 95% confidence interval, 1.020-1.408; P = 0.0272). In contrast, the DFS was similar between the two locations. The present study confirmed that the tumor location was a risk factor for the OS in patients who underwent curative treatment for colon cancer. Tumor location may, therefore, need to be considered a stratification factor in future phase III trials of colon cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Analysis of regional timelines to set up a global phase III clinical trial in breast cancer: the adjuvant lapatinib and/or trastuzumab treatment optimization experience.

    Science.gov (United States)

    Metzger-Filho, Otto; de Azambuja, Evandro; Bradbury, Ian; Saini, Kamal S; Bines, José; Simon, Sergio D; Dooren, Veerle Van; Aktan, Gursel; Pritchard, Kathleen I; Wolff, Antonio C; Smith, Ian; Jackisch, Christian; Lang, Istvan; Untch, Michael; Boyle, Frances; Xu, Binghe; Baselga, Jose; Perez, Edith A; Piccart-Gebhart, Martine

    2013-01-01

    This study measured the time taken for setting up the different facets of adjuvant lapatinib and/or trastuzumab treatment optimization (ALTTO), an nternational phase III study being conducted in 44 participating countries. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank's criteria. South America had a significantly longer time to RA approval (median: 236 days, range: 21-257 days) than Europe (median: 52 days, range: 0-151 days), North America (median: 26 days, range: 22-30 days), and Asia-Pacific (median: 62 days, range: 37-75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21-257 days) than high-income (median: 47 days, range: 0-112 days) and lower-middle income economies (median: 57 days, range: 37-62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0-174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26-412 days). This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research.

  15. Beaver Valley Unit 1, United States of America, 2007. Annex III. Description of Selected Open Phase Events

    International Nuclear Information System (INIS)

    2016-01-01

    On 27 Nov. 2007, during a non-routine walkdown of the off-site switchyard to investigate line voltage differences, the licensee discovered that the Phase A conductor of a 138 kV off-site power circuit of the Beaver Valley Power Station Unit 1 had broken off in the switchyard. This break occurred between the off-site feeder breaker and the line running on-site to the A train system station service transformer, located inside the site security fence. The terminal broke on the switchyard side of a revenue-metering current transformer/voltage transformer installed in 2006 to track the station’s power usage through this line. During normal power operation, no appreciable current goes through this 138 kV line because the unit generator normally powers the station buses (loads). The licensee determined that the break on the 138 kV Phase A had occurred 26 days earlier and, therefore, had not been restored within 72 h as required by technical specifications.

  16. Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

    Directory of Open Access Journals (Sweden)

    Eichbaum Michael H

    2011-01-01

    Full Text Available Abstract Background The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. Methods/design The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border, heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival. Discussion Intensity-modulated WAR provides

  17. Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT) in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

    International Nuclear Information System (INIS)

    Rochet, Nathalie; Debus, Juergen; Kieser, Meinhard; Sterzing, Florian; Krause, Sonja; Lindel, Katja; Harms, Wolfgang; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof

    2011-01-01

    The prognosis for patients with advanced FIGO stage III epithelial ovarian cancer remains poor despite the aggressive standard treatment, consisting of maximal cytoreductive surgery and platinum-based chemotherapy. The median time to recurrence is less than 2 years, with a 5-years survival rate of -20-25%. Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR) as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT) has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1 cm-outer border), heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival. Intensity-modulated WAR provides a new promising option in the consolidation treatment of

  18. PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer

    International Nuclear Information System (INIS)

    Owadally, Waheeda; Hurt, Chris; Timmins, Hayley; Parsons, Emma; Townsend, Sarah; Patterson, Joanne; Hutcheson, Katherine; Powell, Ned; Beasley, Matthew; Palaniappan, Nachi; Robinson, Max; Jones, Terence M.; Evans, Mererid

    2015-01-01

    Human papillomavirus-positive oropharyngeal squamous cell carcinoma is increasing in incidence worldwide. Current treatments are associated with high survival rates but often result in significant long-term toxicities. In particular, long-term dysphagia has a negative impact on patient quality of life and health. The aim of PATHOS is to determine whether reducing the intensity of adjuvant treatment after minimally invasive transoral surgery in this favourable prognosis disease will result in better long-term swallowing function whilst maintaining excellent disease-specific survival outcomes. The study is a multicentre phase II/III randomised controlled trial for patients with biopsy-proven Human papillomavirus-positive oropharyngeal squamous cell cancer staged T1-T3 N0-N2b with a primary tumour that is resectable via a transoral approach. Following transoral surgery and neck dissection, patients are allocated into three groups based on pathological risk factors for recurrence. Patients in the low-risk pathology group will receive no adjuvant treatment, as in standard practice. Patients in the intermediate-risk pathology group will be randomised to receive either standard dose post-operative radiotherapy (control) or reduced dose radiotherapy. Patients in the high-risk pathology group will be randomised to receive either post-operative chemoradiotherapy (control) or radiotherapy alone. The primary outcome of the phase II study is patient reported swallowing function measured using the MD Anderson Dysphagia Inventory score at 12 months post-treatment. If the phase II study is successful, PATHOS will proceed to a phase III non-inferiority trial with overall survival as the primary endpoint. PATHOS is a prospective, randomised trial for Human papillomavirus-positive oropharyngeal cancer, which represents a different disease entity compared with other head and neck cancers. The trial aims to demonstrate that long-term dysphagia can be lessened by reducing the intensity

  19. A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the radiation therapy oncology group (RTOG) 9104

    International Nuclear Information System (INIS)

    Murray, Kevin J.; Scott, Charles; Greenberg, Harvey M.; Emami, Bahman; Seider, Michael; Vora, Nayana L.; Olson, Craig; Whitton, Anthony; Movsas, Benjamin; Curran, Walter

    1997-01-01

    Purpose: To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. Methods and Materials: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. Results: The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary

  20. PLATEAU IRIS SYNDROME--CASE SERIES.

    Science.gov (United States)

    Feraru, Crenguta Ioana; Pantalon, Anca Delia; Chiselita, Dorin; Branisteanu, Daniel

    2015-01-01

    Plateau iris is characterized by closing the anterior chamber angle due to a large ciliary body or due to its anterior insertion that alters the position of iris periphery in respect to the trabecular meshwork. There are two aspects that need to be differentiated: plateau iris configuration and plateau iris syndrome. The first describes a situation when the iris root is flat and the anterior chamber is not shallow, the latter refers to a post laser iridotomy condition in which a patent iridotomy has removed the relative pupillary block, but goniscopically confirmed angle closure recurs without central shallowing of the anterior chamber. Isolated plateau iris syndrome is rare compared to plateau iris configuration. We hereby present two case reports of plateau iris syndrome in young patients who came to an ophthalmologic consult by chance.

  1. Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone.

    Science.gov (United States)

    Terra, Steven G; Focht, Kristen; Davies, Melanie; Frias, Juan; Derosa, Giuseppe; Darekar, Amanda; Golm, Gregory; Johnson, Jeremy; Saur, Didier; Lauring, Brett; Dagogo-Jack, Sam

    2017-05-01

    To conduct a phase III study to evaluate the efficacy and safety of ertugliflozin monotherapy in people with type 2 diabetes. This was a 52-week, double-blind, multicentre, randomized, parallel-group study with a 26-week, placebo-controlled treatment period (phase A), followed by a 26-week active-controlled treatment period (phase B) in 461 men and women, aged ≥18 years with inadequate glycaemic control (glycated haemoglobin [HbA1c] concentration 7.0% to 10.5% [53-91 mmol/mol], inclusive) despite diet and exercise. Results from phase A are reported in the present paper. The primary endpoint was the change in HbA1c from baseline to week 26. At week 26, the placebo-adjusted least squares mean HbA1c changes from baseline were -0.99% and -1.16% for the ertugliflozin 5 and 15 mg doses, respectively ( P  < .001 for both doses). The odds of having HbA1c <7.0% (53 mmol/mol) were significantly greater in the ertugliflozin 5 and 15 mg groups compared with the placebo group. Both doses of ertugliflozin significantly lowered fasting plasma glucose and 2-hour postprandial glucose levels and body weight. The placebo-adjusted differences in changes from baseline in systolic blood pressure were not statistically significant. A higher incidence of genital mycotic infections occurred in men and women treated with ertugliflozin compared with placebo. There was no significant difference between treatments in the proportion of participants with symptomatic hypoglycaemia or adverse events associated with urinary tract infection or hypovolaemia. Ertugliflozin 5 and 15 mg treatment for 26 weeks provides effective glycaemic control, reduces body weight and is generally well tolerated, when used as monotherapy. © 2017 John Wiley & Sons Ltd.

  2. Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Han, Ji-Youn; Lee, Soo Hyun; Lee, Geon Kook; Yun, Tak; Lee, Young Joo; Hwang, Kum Hui; Kim, Jin Young; Kim, Heung Tae

    2015-03-01

    Vorinostat has been shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated non-small cell lung cancer (NSCLC). A 3 + 3 dose-escalation design was used to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Three dose levels were tested: 250 mg/day gefitinib on days 1-28 and 200, 300 or 400 mg/day vorinostat on days 1-7, and 15-21 out of every 28 days. The primary endpoint was median progression-free survival (PFS). Fifty-two patients were enrolled and treated (43 in phase II). The median age was 59 years, 28 patients were male, 44 had adenocarcinoma, 29 had never smoked, and 36 had undergone one prior treatment. Twenty-two patients exhibited sensitive EGFR mutations. Planned dose escalation was completed without reaching the MTD. The RP2D was 250 mg gefitinib and 400 mg vorinostat. In 43 assessable patients in phase II, the median PFS was 3.2 months; the overall survival (OS) was 19.0 months. There were 16 partial responses and six cases of stable disease. In EGFR-mutant NSCLC, response rate was 77 %, median PFS was 9.1 months, and median OS was 24.1 months. The most common adverse events were anorexia and diarrhea. Treatment with 250 mg gefitinib daily with biweekly 400 mg/day vorinostat was feasible and well tolerated. In an unselected patient population, this combination dose did not improve PFS. However, this combination showed a potential for improving efficacy of gefitinib in EGFR-mutant NSCLC (NCT01027676).

  3. Quantum dynamics calculations using symmetrized, orthogonal Weyl-Heisenberg wavelets with a phase space truncation scheme. III. Representations and calculations.

    Science.gov (United States)

    Poirier, Bill; Salam, A

    2004-07-22

    In a previous paper [J. Theo. Comput. Chem. 2, 65 (2003)], one of the authors (B.P.) presented a method for solving the multidimensional Schrodinger equation, using modified Wilson-Daubechies wavelets, and a simple phase space truncation scheme. Unprecedented numerical efficiency was achieved, enabling a ten-dimensional calculation of nearly 600 eigenvalues to be performed using direct matrix diagonalization techniques. In a second paper [J. Chem. Phys. 121, 1690 (2004)], and in this paper, we extend and elaborate upon the previous work in several important ways. The second paper focuses on construction and optimization of the wavelength functions, from theoretical and numerical viewpoints, and also examines their localization. This paper deals with their use in representations and eigenproblem calculations, which are extended to 15-dimensional systems. Even higher dimensionalities are possible using more sophisticated linear algebra techniques. This approach is ideally suited to rovibrational spectroscopy applications, but can be used in any context where differential equations are involved.

  4. Solid-phase synthesis of polynucleotides. III. Synthesis of polynucleotides with defined sequences by the block coupling phosphotriester method.

    OpenAIRE

    Miyoshi, K; Huang, T; Itakura, K

    1980-01-01

    Preparation of the three hexadecanucleotides, dGpTpApTpCpApCpGpApGpGpCpCpCpTpT, dCpGpApCpGpApGpCpGpTpGpApCpApCpC and cTpGpCpCpGpGpCpCpApCpGpApTpGpCpG, is described by a rapid and simple solid-phase method on polyacrylamide supports. The synthesis were performed by the extension of the method described in the previous paper using di and trinucleotides of defined sequences as an incoming 3'-phosphodiester unit. Although the coupling yields to form phosphotriester bonds are slightly lower than t...

  5. Phase I/II Multi-Institutional Study of Percutaneous Radiofrequency Ablation for Painful Osteoid Osteoma (JIVROSG-0704)

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Masaya, E-mail: mmiyazak@gunma-u.ac.jp [Gunma University Hospital, Department of Interventional Radiology and Clinical Ultrasound Center (Japan); Arai, Yasuaki [National Center Hospital, Division of Diagnostic Radiology (Japan); Myoui, Akira [Osaka University Hospital, Medical Center for Translational Research (Japan); Gobara, Hideo [Okayama University Medical School, Department of Radiology (Japan); Sone, Miyuki [National Center Hospital, Division of Diagnostic Radiology (Japan); Rosenthal, Daniel I. [Harvard Medical School, Department of Radiology, Massachusetts General Hospital (United States); Tsushima, Yoshito [Gunma University Hospital, Department of Interventional Radiology and Clinical Ultrasound Center (Japan); Kanazawa, Susumu [Okayama University Medical School, Department of Radiology (Japan); Ehara, Shigeru [Iwate Medical University School of Medicine, Department of Radiology (Japan); Endo, Keigo [Gunma University Hospital, Department of Interventional Radiology and Clinical Ultrasound Center (Japan)

    2016-10-15

    PurposeThis multicenter prospective study was conducted to evaluate the safety and efficacy of percutaneous radiofrequency ablation (RFA) for painful osteoid osteoma (OO).Materials and MethodsPatients with OO (femur: n = 17, tibia: n = 2, humerus: n = 1, rib: n = 1) were enrolled and treated with RFA. In phase I, nine patients were evaluated for safety. In phase II, 12 patients were accrued, and an intent-to-treat analysis was performed on all patients. The primary endpoint was to evaluate the treatment safety. The secondary endpoint was to evaluate the efficacy for pain relief by the visual analogue scale (VAS) at 4 weeks after RFA. Treatment efficacy was classified as significantly effective (SE) when VAS score decreased by ≥5 or score was <2, moderately effective when VAS score decreased by <5–≥2 and score was ≥2, and not effective (NE) when VAS score decreased by <2 or score was increased. Cases where the need for analgesics increased after treatment were also NE.ResultsRFA procedures were completed in all patients. Minor adverse effects (AEs) were observed as 4.8–14.3 % in 12 patients, and no major AEs were observed. Mean VAS score was 7.1 before treatment, 1.6 at 1 week, 0.3 at 4 weeks, and 0.2 at 3 months. All procedures were classified as SE. Pain recurrence was not noted in any patient during follow-up (mean: 15.1 months).ConclusionRFA is a safe, highly effective, and fast-acting treatment for painful extraspinal OO. Future studies with a greater number of patients are needed.

  6. Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study

    International Nuclear Information System (INIS)

    Junius, Sara; Haustermans, Karin; Bussels, Barbara; Oyen, Raymond; Vanstraelen, Bianca; Depuydt, Tom; Verstraete, Jan; Joniau, Steven; Van Poppel, Hendrik

    2007-01-01

    To assess acute (primary endpoint) and late toxicity, quality of life (QOL), biochemical or clinical failure (secondary endpoints) of a hypofractionated IMRT schedule for prostate cancer (PC). 38 men with localized PC received 66 Gy (2.64 Gy) to prostate,2 Gy to seminal vesicles (50 Gy total) using IMRT. Acute toxicity was evaluated weekly during radiotherapy (RT), at 1–3 months afterwards using RTOG acute scoring system. Late side effects were scored at 6, 9, 12, 16, 20, 24 and 36 months after RT using RTOG/EORTC criteria. Quality of life was assessed by EORTC-C30 questionnaire and PR25 prostate module. Biochemical failure was defined using ASTRO consensus and nadir+2 definition, clinical failure as local, regional or distant relapse. None experienced grade III-IV toxicity. 10% had no acute genito-urinary (GU) toxicity, 63% grade I; 26% grade II. Maximum acute gastrointestinal (GI) scores 0, I, II were 37%, 47% and 16%. Maximal acute toxicity was reached weeks 4–5 and resolved within 4 weeks after RT in 82%. Grade II rectal bleeding needing coagulation had a peak incidence of 18% at 16 months after RT but is 0% at 24–36 months. One developed a urethral stricture at 2 years (grade II late GU toxicity) successfully dilated until now. QOL urinary symptom scores reached a peak incidence 1 month after RT but normalized 6 months later. Bowel symptom scores before, at 1–6 months showed similar values but rose slowly 2–3 years after RT. Nadir of sexual symptom scores was reached 1–6 months after RT but improved 2–3 years later as well as physical, cognitive and role functional scales. Emotional, social functional scales were lowest before RT when diagnosis was given but improved later. Two years after RT global health status normalized. This hypofractionated IMRT schedule for PC using 25 fractions of 2.64 Gy did not result in severe acute side effects. Until now late urethral, rectal toxicities seemed acceptable as well as failure rates. Detailed analysis of

  7. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

    Science.gov (United States)

    Hoskins, P; Vergote, I; Cervantes, A; Tu, D; Stuart, G; Zola, P; Poveda, A; Provencher, D; Katsaros, D; Ojeda, B; Ghatage, P; Grimshaw, R; Casado, A; Elit, L; Mendiola, C; Sugimoto, A; D'Hondt, V; Oza, A; Germa, J R; Roy, M; Brotto, L; Chen, D; Eisenhauer, E A

    2010-10-20

    Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and

  8. Air quality and climate change, Topic 3 of the Model Inter-Comparison Study for Asia Phase III (MICS-Asia III – Part 1: Overview and model evaluation

    Directory of Open Access Journals (Sweden)

    M. Gao

    2018-04-01

    Full Text Available Topic 3 of the Model Inter-Comparison Study for Asia (MICS-Asia Phase III examines how online coupled air quality models perform in simulating high aerosol pollution in the North China Plain region during wintertime haze events and evaluates the importance of aerosol radiative and microphysical feedbacks. A comprehensive overview of the MICS-Asia III Topic 3 study design, including descriptions of participating models and model inputs, the experimental designs, and results of model evaluation, are presented. Six modeling groups from China, Korea and the United States submitted results from seven applications of online coupled chemistry–meteorology models. Results are compared to meteorology and air quality measurements, including data from the Campaign on Atmospheric Aerosol Research Network of China (CARE-China and the Acid Deposition Monitoring Network in East Asia (EANET. The correlation coefficients between the multi-model ensemble mean and the CARE-China observed near-surface air pollutants range from 0.51 to 0.94 (0.51 for ozone and 0.94 for PM2.5 for January 2010. However, large discrepancies exist between simulated aerosol chemical compositions from different models. The coefficient of variation (SD divided by the mean can reach above 1.3 for sulfate in Beijing and above 1.6 for nitrate and organic aerosols in coastal regions, indicating that these compositions are less consistent from different models. During clean periods, simulated aerosol optical depths (AODs from different models are similar, but peak values differ during severe haze events, which can be explained by the differences in simulated inorganic aerosol concentrations and the hygroscopic growth efficiency (affected by varied relative humidity. These differences in composition and AOD suggest that future models can be improved by including new heterogeneous or aqueous pathways for sulfate and nitrate formation under hazy conditions, a secondary organic aerosol (SOA

  9. Phase II Results of RTOG 0537: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

    Science.gov (United States)

    Wong, Raimond K. W.; James, Jennifer L.; Sagar, Stephen; Wyatt, Gwen; Nguyen-Tân, Phuc Felix; Singh, Anurag K.; Lukaszczyk, Barbara; Cardinale, Francis; Yeh, Alexander M.; Berk, Lawrence

    2011-01-01

    Purpose This phase II component of a multi-institutional phase II/III randomized trial assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Methods Head and neck cancer patients who were 3–24 months from completing radiotherapy ± chemotherapy (RT±C) and experiencing xerostomia symptoms with basal whole saliva production ≥0.1 ml/min and without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 over 12 weeks) using a Codetron™ unit. The primary objective assessed the feasibility of ALTENS treatment. A patient was considered compliant if 19/24 ALTENS were delivered, with a targeted 85% compliance rate. Secondary objectives measured treatment-related toxicities and ALTENS effect on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Results Of 48 accrued patients, 47 were evaluable. Median age was 60 years; 84% were male, 70% completed RT±C for > 12 months and 21% had received prior pilocarpine. All ALTENS sessions were completed in 34 patients, but 9 and 1 completed 20–23 and 19 sessions respectively, representing a 94% total compliance rate. 6-month XeQOLS scores were available for 35 patients; 30 (86%) achieved a positive treatment response with a mean reduction of 35.9% (SD 36.1). Five patients developed grade 1–2 gastrointestinal toxicity and one had grade 1 pain event. Conclusions ALTENS treatment for radiation-induced xerostomia can be uniformly delivered in a cooperative multicenter setting and has possible beneficial treatment response. Given these results, the phase III component of this study was initiated. PMID:22252927

  10. Effects of Mg/Ga and V/III source ratios on hole concentration of N-polar (000\\bar{1}) p-type GaN grown by metalorganic vapor phase epitaxy

    Science.gov (United States)

    Nonoda, Ryohei; Shojiki, Kanako; Tanikawa, Tomoyuki; Kuboya, Shigeyuki; Katayama, Ryuji; Matsuoka, Takashi

    2016-05-01

    The effects of growth conditions such as Mg/Ga and V/III ratios on the properties of N-polar (000\\bar{1}) p-type GaN grown by metalorganic vapor phase epitaxy were studied. Photoluminescence spectra from Mg-doped GaN depended on Mg/Ga and V/III ratios. For the lightly doped samples, the band-to-acceptor emission was observed at 3.3 eV and its relative intensity decreased with increasing V/III ratio. For the heavily doped samples, the donor-acceptor pair emission was observed at 2.8 eV and its peak intensity monotonically decreased with V/III ratio. The hole concentration was maximum for the Mg/Ga ratio. This is the same tendency as in group-III polar (0001) growth. The V/III ratio also reduced the hole concentration. The higher V/III ratio reduced the concentration of residual donors such as oxygen by substituting nitrogen atoms. The surface became rougher with increasing V/III ratio and the hillock density increased.

  11. Results of tests and studies of American materials in the channel of the MHD facility U-02 (Phase III)

    International Nuclear Information System (INIS)

    Burenkov, D.K.; Borodina, T.I.; Vysotsky, D.A.; Zalkind, V.I.; Kirillov, V.V.; Romanov, A.I.; Telegin, G.P.; Strekalov, N.V.

    1978-10-01

    In accordance with the US--USSR Cooperative Program in MHD joint US--USSR tests were conducted in May 1978 at the U-02 facility of an MHD generator section consisting of U.S.-built electrode blocks and USSR-built insulating walls. The main purpose of the experiment was to conduct continuous 100-hour duration tests of materials and structures of electrode blocks; in particular, to study the behavior of ceramic electrodes and insulators in operating conditions of an MHD generator, the electro-physical and thermal characteristics of the working section as a whole and electrodes in particular, and to analyze the change in the phase composition and structure of materials during the test. The main thrust of the experiment was a study of electrode material behavior. Six varieties of electrodes based on doped lanthanum chromite were tested and investigated. The electrodes were made of fine grained, hot-pressed mass (the porosity of the ceramic was 2 to 3%). The interelectrode insulators were made of magnesial and magnesial-spinel ceramic also manufactured by the hot pressing method. Results are presented and discussed

  12. Kryptonate-based instrumentation development for automobile exhaust pollutants. Phase III report: design and construction of four (4) experimental models

    International Nuclear Information System (INIS)

    Goodman, P.; Donaghue, T.

    This phase of the program encompasses the design, construction and evaluation of four (4) prototype instruments for the detection of automobile exhaust pollutant. These instruments employ the radio release mechanism utilized by Panametrics in detection of various trace gases. The prototype instruments are of two (2) designs. One design is operable from a power source supplied by an automobile battery. The second design is operable from 110 volts AC power. Successful evaluation in the laboratory as well as with various automobiles were performed with both type instruments. Scale-up of the quantity of sensor material prepared introduced unexpected problems with respect to detection lifetime which were not satisfactorily resolved within the time and funds available to the program. Nevertheless, a Kryptonate-based instrument using a single detection method for the measurement of hydrocarbons, CO and NO/sub x/ as pollutants by automobile exhausts was shown to be operable with actual automobile exhausts, to provide more than adequate sensitivity for inspection purposes, and to provide response and recovery times for full scale reading in the range 10-15 secs. (auth)

  13. Treatment-related death in patients with small-cell lung cancer in phase III trials over the last two decades.

    Directory of Open Access Journals (Sweden)

    Nobuaki Ochi

    Full Text Available INTRODUCTION: Treatment-related death (TRD remains a serious problem in small-cell lung cancer (SCLC, despite recent improvements in supportive care. However, few studies have formally assessed time trends in the proportion of TRD over the past two decades. The aim of this study was to determine the frequency and pattern of TRD over time. METHODS: We examined phase 3 trials conducted between 1990 and 2010 to address the role of systemic treatment for SCLC. The time trend was assessed using linear regression analysis. RESULTS: In total, 97 trials including nearly 25,000 enrolled patients were analyzed. The overall TRD proportion was 2.95%. Regarding the time trend, while it was not statistically significant, it tended to decrease, with a 0.138% decrease per year and 2.76% decrease per two decades. The most common cause of death was febrile neutropenia without any significant time trend in its incidence over the years examined (p = 0.139. However, deaths due to febrile neutropenia as well as all causes in patients treated with non-platinum chemotherapy increased significantly (p = 0.033. CONCLUSIONS: The overall TRD rate has been low, but not negligible, in phase III trials for SCLC over the past two decades.

  14. Heterogeneous FDG-guided dose-escalation for locally advanced NSCLC (the NARLAL2 trial): Design and early dosimetric results of a randomized, multi-centre phase-III study

    DEFF Research Database (Denmark)

    Møller, Ditte Sloth; Nielsen, Tine Bjørn; Brink, Carsten

    2017-01-01

    Background and purpose: Local recurrence is frequent in locally advanced NSCLC and is primarily located in FDG-avid parts of tumour and lymph nodes. Aiming at improving local control without increasing toxicity, we designed a multi-centre phase-III trial delivering inhomogeneous dose-escalation d......Background and purpose: Local recurrence is frequent in locally advanced NSCLC and is primarily located in FDG-avid parts of tumour and lymph nodes. Aiming at improving local control without increasing toxicity, we designed a multi-centre phase-III trial delivering inhomogeneous dose...

  15. Iceberg incursions across Campbell Plateau

    International Nuclear Information System (INIS)

    Northcote, L.; Neil, H.; Carter, L.

    1999-01-01

    The last reported sighting of icebergs off eastern New Zealand was on 28th October, 1892, at the Chatham Islands. Prior to that time, the SW Pacific Ocean periodically hosted flotillas of icebergs, as revealed by a palaeoceanographic analysis of 8 cores from the Campbell Plateau. Stable isotope stratigraphy, coupled with down-core measurements of magnetic susceptibility, grain size, calcium carbonate and ice-rafted debris, highlight climate-related fluctuations in iceberg activity back to at least marine isotope stage (MIS) 6 - our longest complete record. (author)

  16. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.

    Science.gov (United States)

    Talley, N J; Tack, J; Ptak, T; Gupta, R; Giguère, M

    2008-06-01

    Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). In this population with FD, itopride did not show a difference in symptom response from placebo.

  17. Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Bazarbashi, Shouki; Aljubran, Ali; Alzahrani, Ahmad; Mohieldin, Ahmed; Soudy, Hussein; Shoukri, Mohammed

    2015-01-01

    Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m 2 . Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity

  18. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

    Science.gov (United States)

    Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

    2014-08-21

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

  19. Observation of the Zero Hall Plateau in a Quantum Anomalous Hall Insulator

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Yang; Feng, Xiao; Ou, Yunbo; Wang, Jing; Liu, Chang; Zhang, Liguo; Zhao, Dongyang; Jiang, Gaoyuan; Zhang, Shou-Cheng; He, Ke; Ma, Xucun; Xue, Qi-Kun; Wang, Yayu

    2015-09-16

    We report experimental investigations on the quantum phase transition between the two opposite Hall plateaus of a quantum anomalous Hall insulator. We observe a well-defined plateau with zero Hall conductivity over a range of magnetic field around coercivity when the magnetization reverses. The features of the zero Hall plateau are shown to be closely related to that of the quantum anomalous Hall effect, but its temperature evolution exhibits a significant difference from the network model for a conventional quantum Hall plateau transition. We propose that the chiral edge states residing at the magnetic domain boundaries, which are unique to a quantum anomalous Hall insulator, are responsible for the novel features of the zero Hall plateau.

  20. Does Concurrent Radiochemotherapy Affect Cosmetic Results in the Adjuvant Setting After Breast-Conserving Surgery? Results of the ARCOSEIN Multicenter, Phase III Study: Patients' and Doctors' Views

    International Nuclear Information System (INIS)

    Toledano, Alain H.; Bollet, Marc A.; Fourquet, Alain; Azria, David; Gligorov, Joseph; Garaud, Pascal; Serin, Daniel; Bosset, Jean-Francois; Miny-Buffet, Joelle; Favre, Anne; Le Foch, Olivier; Calais, Gilles

    2007-01-01

    Purpose: To evaluate the cosmetic results of sequential vs. concurrent adjuvant chemotherapy with radiotherapy after breast-conserving surgery for breast cancer, and to compare ratings by patients and physicians. Methods and Materials: From 1996 to 2000, 716 patients with Stage I-II breast cancers were included in a multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast-conserving surgery with axillary dissection, sequential treatment with chemotherapy first followed by radiotherapy vs. chemotherapy administered concurrently with radiotherapy. Cosmetic results with regard to both the overall aspect of the breast and specific changes (color, scar) were evaluated in a total of 214 patients (107 in each arm) by means of questionnaires to both the patient and a physician whose rating was blinded to treatment allocation. Results: Patients' overall satisfaction with cosmesis was not statistically different between the two arms, with approximately 92% with at least satisfactory results (p = 0.72), although differences between the treated and untreated breasts were greater after the concurrent regimen (29% vs. 14% with more than moderate differences; p 0.0015). Physician assessment of overall cosmesis was less favorable, with lower rates of at least satisfactory results in the concurrent arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall satisfaction with cosmesis between patients and doctors was only fair (κ = 0.62). Conclusion: After breast-conserving surgery, the concurrent use of chemotherapy with radiotherapy is significantly associated with greater differences between the breasts. These differences do not translate into patients' lessened satisfaction with cosmesis

  1. A phase ii study of concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide for elderly patients with stage iii non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Shibamoto, Yuta; Milicic, Biljana; Milisavljevic, Slobodan; Nikolic, Nebojsa; Dagovic, Aleksandar; Aleksandrovic, Jasna; Radosavljevic-Asic, Gordana

    1999-01-01

    Purpose: To investigate feasibility, toxicity, and efficacy of accelerated hyperfractionated radiation therapy and concurrent carboplatin/oral etoposide in elderly (> 70 years) patients with stage III non-small-cell lung cancer. Methods and Materials: Between January 1988 and June 1993, a total of 58 patients entered a phase II study. Carboplatin (400 mg/m 2 ) was given intravenously on days 1 and 29, and etoposide (50 mg/m 2 ) was given orally on days 1-21 and 29-42. Accelerated hyperfractionated radiotherapy was administered starting on day 1, with a total dose of 51 Gy in 34 fractions over 3.5 weeks. Results: In 55 evaluable patients, the complete response rate was 27% and the overall response rate was 65%. For the 55 patients, the median survival time was 10 months, and the 1-, 2-, and 5-year survival rates were 45%, 24%, and 9.1%, respectively. The median time until relapse was 8 months and the 1-, 2-, and 5-year relapse-free survival rates were 45%, 20%, and 9.1%, respectively. The median time to local recurrence was 14 months and the 5-year local control rate was 13%; the median time to distant metastasis was 18 months and the 5-year distant metastasis-free rate was 15%. Hematological, esophageal, and bronchopulmonary acute grade 3 or 4 toxicities were observed in 22%, 7%, and 4% of the patients, respectively. There was no grade 5 toxicity or late grade ≥ 3 toxicity. Conclusion: Concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide produced relatively low and acceptable toxicity. The survival results appeared to be comparable to those obtained in nonelderly patients with stage III non-small-cell lung cancer treated by full-dose radiation

  2. Four new Gammarus species from Tibetan Plateau with a key to Tibetan freshwater gammarids (Crustacea, Amphipoda, Gammaridae

    Directory of Open Access Journals (Sweden)

    Zhonge Hou

    2018-03-01

    Full Text Available Four new species of the genus Gammarus are described and illustrated from Tibetan Plateau. Gammarus altus sp. n. and G. limosus sp. n. are characterized by pereopods III–IV with a few short setae and uropod III with marginal spines accompanied by short setae. Gammarus kangdingensis sp. n. and G. gonggaensis sp. n. are characterized by pereopods III–IV with long straight setae on posterior margins and inner ramus of uropod III 0.4 times as long as outer ramus. Detailed morphological comparisons with related species are discussed. A key to 15 Gammarus species from the Tibetan Plateau and a map of their distributions are provided.

  3. Drilling, Completion, and Data Collection Plans An Assessment of Geological Carbon Sequestration Options in the Illinois Basin: Phase III

    Energy Technology Data Exchange (ETDEWEB)

    Malkewicz, Nicholas; Kirksey, Jim; Finley, Robert

    2015-05-01

    execution phases of the project. The implementation included an HSE Bridging Document, which served to unify the HSE policies of the project partners and key subcontractors. The HSE plan and actual HSE results are presented in this document. There were no recordable HSE incidents during the project. A detailed logging program was developed based on project needs. The log data were acquired in accordance with the plan, and both the plan and log results are presented in this report. Log data were heavily utilized by the research staff, modelers, reservoir engineers, and for technical and permitting efforts. 5 Several key lessons were learned during the project: • Safety in operations and execution is paramount and is only achieved through proper planning and behavior control. The certainty of this was reinforced through implementation of this lesson and the resultant flawless HSE performance during the project. • Losses of drilling fluid circulation were larger than anticipated within the Potosi Formation. Circulation was only recovered through cementing the loss zones. • When possible, minimizing complexity in permit requirements and well designs is preferable. • The size of the wells were outside of the standard experience and expertise typical within the basin, and therefore required substantial planning and ramp-up of contractors and partners to meet project objectives. • With multiple stakeholders and research partners, establishing objectives and requirements early and adhering to change request procedures throughout the project are critical to manage competing data and sampling objectives that may be detrimental to overall progress. The well construction and completion operations were successfully executed, with all wells built in a manner that achieved excellent wellbore integrity. Log planning involved a number of stakeholders and technical specialists. Data collection from logging, coring, and testing was excellent. Time and effort spent with the

  4. Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

    Science.gov (United States)

    Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

    2013-12-02

    Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All

  5. Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study

    International Nuclear Information System (INIS)

    Nikoghosyan, Anna V; Rauch, Geraldine; Münter, Marc W; Jensen, Alexandra D; Combs, Stephanie E; Kieser, Meinhard; Debus, Jürgen

    2010-01-01

    Low and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours. The study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial. Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points. Up to now it was impossible to compare two different

  6. Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program.

    Science.gov (United States)

    Barret, Juan P; Podmelle, Fred; Lipový, Břetislav; Rennekampff, Hans-Oliver; Schumann, Hauke; Schwieger-Briel, Agnes; Zahn, Tobias R; Metelmann, Hans-Robert

    2017-09-01

    The clinical significance of timely re-epithelialization is obvious in burn care, since delayed wound closure is enhancing the risk of wound site infection and extensive scarring. Topical treatments that accelerate wound healing are urgently needed to reduce these sequelae. Evidence from preliminary studies suggests that betulin can accelerate the healing of different types of wounds, including second degree burns and split-thickness skin graft wounds. The goal of this combined study program consisting of two randomized phase III clinical trials in parallel is to evaluate whether a topical betulin gel (TBG) is accelerating re-epithelialization of split-thickness skin graft (STSG) donor site wounds compared to standard of care. Two parallel blindly evaluated, randomised, controlled, multicentre phase III clinical trials were performed in adults undergoing STSG surgery (EudraCT nos. 2012-003390-26 and 2012-000777-23). Donor site wounds were split into two equal halves and randomized 1:1 to standard of care (a non-adhesive moist wound dressing) or standard of care plus TBG consisting of 10% birch bark extract and 90% sunflower oil (Episalvan, Birken AG, Niefern-Oeschelbronn, Germany). The primary efficacy assessment was the intra-individual difference in time to wound closure assessed from digital photographs by three blinded experts. A total of 219 patients were included and treated in the two trials. Wounds closed faster with TBG than without it (15.3 vs. 16.5 days; mean intra-individual difference=-1.1 days [95% CI, -1.5 to -0.7]; p<0.0001). This agreed with unblinded direct clinical assessment (difference=-2.1 days [95% CI, -2.7 to -1.5]; p<0.0001). Adverse events possibly related to treatment were mild or moderate and mostly at the application site. TBG accelerates re-epithelialization of partial thickness wounds compared to the current standard of care, providing a well-tolerated contribution to burn care in practice. Copyright © 2017 The Authors. Published by

  7. Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma.

    Science.gov (United States)

    Huang, Yan; Liang, Wenhua; Yang, Yunpeng; Zhao, Liping; Zhao, Hongyun; Wu, Xuan; Zhao, Yuanyuan; Zhang, Yang; Zhang, Li

    2016-07-13

    This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab (®)-paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m(2) on day 1; 2) IV nab-paclitaxel 140 mg/m(2) on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m(2) on day 1. Treatment continued for 4-6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6-12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. ClinicalTrials.gov ID: NCT01735409 . The trial was registered on November 20th, 2012.

  8. Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Huang, Yan; Liang, Wenhua; Yang, Yunpeng; Zhao, Liping; Zhao, Hongyun; Wu, Xuan; Zhao, Yuanyuan; Zhang, Yang; Zhang, Li

    2016-01-01

    This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab ® -paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m 2 on day 1; 2) IV nab-paclitaxel 140 mg/m 2 on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m 2 on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m 2 on day 1. Treatment continued for 4–6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6–12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. ClinicalTrials.gov ID: NCT01735409. The trial was registered on November 20th, 2012. The online version of this article (doi:10.1186/s12885

  9. Assessment of severe malaria in a multicenter, phase III, RTS, S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care.

    Science.gov (United States)

    Vekemans, Johan; Marsh, Kevin; Greenwood, Brian; Leach, Amanda; Kabore, William; Soulanoudjingar, Solange; Asante, Kwaku Poku; Ansong, Daniel; Evans, Jennifer; Sacarlal, Jahit; Bejon, Philip; Kamthunzi, Portia; Salim, Nahya; Njuguna, Patricia; Hamel, Mary J; Otieno, Walter; Gesase, Samwel; Schellenberg, David

    2011-08-04

    An effective malaria vaccine, deployed in conjunction with other malaria interventions, is likely to substantially reduce the malaria burden. Efficacy against severe malaria will be a key driver for decisions on implementation. An initial study of an RTS, S vaccine candidate showed promising efficacy against severe malaria in children in Mozambique. Further evidence of its protective efficacy will be gained in a pivotal, multi-centre, phase III study. This paper describes the case definitions of severe malaria used in this study and the programme for standardized assessment of severe malaria according to the case definition. Case definitions of severe malaria were developed from a literature review and a consensus meeting of expert consultants and the RTS, S Clinical Trial Partnership Committee, in collaboration with the World Health Organization and the Malaria Clinical Trials Alliance. The same groups, with input from an Independent Data Monitoring Committee, developed and implemented a programme for standardized data collection.The case definitions developed reflect the typical presentations of severe malaria in African hospitals. Markers of disease severity were chosen on the basis of their association with poor outcome, occurrence in a significant proportion of cases and on an ability to standardize their measurement across research centres. For the primary case definition, one or more clinical and/or laboratory markers of disease severity have to be present, four major co-morbidities (pneumonia, meningitis, bacteraemia or gastroenteritis with severe dehydration) are excluded, and a Plasmodium falciparum parasite density threshold is introduced, in order to maximize the specificity of the case definition. Secondary case definitions allow inclusion of co-morbidities and/or allow for the presence of parasitaemia at any density. The programmatic implementation of standardized case assessment included a clinical algorithm for evaluating seriously sick children

  10. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies.

    Science.gov (United States)

    Platt, Adam; Morten, John; Ji, Qunsheng; Elvin, Paul; Womack, Chris; Su, Xinying; Donald, Emma; Gray, Neil; Read, Jessica; Bigley, Graham; Blockley, Laura; Cresswell, Carl; Dale, Angela; Davies, Amanda; Zhang, Tianwei; Fan, Shuqiong; Fu, Haihua; Gladwin, Amanda; Harrod, Grace; Stevens, James; Williams, Victoria; Ye, Qingqing; Zheng, Li; de Boer, Richard; Herbst, Roy S; Lee, Jin-Soo; Vasselli, James

    2015-03-23

    To determine the prevalence of RET rearrangement genes, RET copy number gains and expression in tumor samples from four Phase III non-small-cell lung cancer (NSCLC) trials of vandetanib, a selective inhibitor of VEGFR, RET and EGFR signaling, and to determine any association with outcome to vandetanib treatment. Archival tumor samples from the ZODIAC ( NCT00312377 , vandetanib ± docetaxel), ZEAL ( NCT00418886 , vandetanib ± pemetrexed), ZEPHYR ( NCT00404924 , vandetanib vs placebo) and ZEST ( NCT00364351 , vandetanib vs erlotinib) studies were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 944 and 1102 patients. The prevalence of RET rearrangements by FISH was 0.7% (95% CI 0.3-1.5%) among patients with a known result. Seven tumor samples were positive for RET rearrangements (vandetanib, n = 3; comparator, n = 4). 2.8% (n = 26) of samples had RET amplification (innumerable RET clusters, or ≥7 copies in > 10% of tumor cells), 8.1% (n = 76) had low RET gene copy number gain (4-6 copies in ≥40% of tumor cells) and 8.3% (n = 92) were RET expression positive (signal intensity ++ or +++ in >10% of tumor cells). Of RET-rearrangement-positive patients, none had an objective response in the vandetanib arm and one patient responded in the comparator arm. Radiologic evidence of tumor shrinkage was observed in two patients treated with vandetanib and one treated with comparator drug. The objective response rate was similar in the vandetanib and comparator arms for patients positive for RET copy number gains or RET protein expression. We have identified prevalence for three RET biomarkers in a population predominated by non-Asians and smokers. RET rearrangement prevalence was lower than previously reported. We found no evidence of a differential benefit for efficacy by IHC and RET gene copy number gains. The low prevalence of RET rearrangements (0.7%) prevents firm conclusions regarding association of vandetanib treatment with

  11. Ten- to 15-year results of the Oxford Phase III mobile unicompartmental knee arthroplasty: a prospective study from a non-designer group.

    Science.gov (United States)

    Lisowski, L A; Meijer, L I; Bekerom, M P J van den; Pilot, P; Lisowski, A E

    2016-10-01

    The interest in unicompartmental knee arthroplasty (UKA) for medial osteoarthritis has increased rapidly but the long-term follow-up of the Oxford UKAs has yet to be analysed in non-designer centres. We have examined our ten- to 15-year clinical and radiological follow-up data for the Oxford Phase III UKAs. Between January 1999 and January 2005 a total of 138 consecutive Oxford Phase III arthroplasties were performed by a single surgeon in 129 patients for medial compartment osteoarthritis (71 right and 67 left knees, mean age 72.0 years (47 to 91), mean body mass index 28.2 (20.7 to 52.2)). Both clinical data and radiographs were prospectively recorded and obtained at intervals. Of the 129 patients, 32 patients (32 knees) died, ten patients (12 knees) were not able to take part in the final clinical and radiological assessment due to physical and mental conditions, but via telephone interview it was confirmed that none of these ten patients (12 knees) had a revision of the knee arthroplasty. One patient (two knees) was lost to follow-up. The mean follow-up was 11.7 years (10 to 15). A total of 11 knees (8%) were revised. The survival at 15 years with revision for any reason as the endpoint was 90.6% (95% confidence interval (CI) 85.2 to 96.0) and revision related to the prosthesis was 99.3% (95% CI 97.9 to 100). The mean total Knee Society Score was 47 (0 to 80) pre-operatively and 81 (30 to 100) at latest follow-up. The mean Oxford Knee Score was 19 (12 to 40) pre-operatively and 42 (28 to 55) at final follow-up. Radiolucency beneath the tibial component occurred in 22 of 81 prostheses (27.2%) without evidence of loosening. This study supports the use of UKA in medial compartment osteoarthritis with excellent long-term functional and radiological outcomes with an excellent 15-year survival rate. Cite this article: Bone Joint J 2016;98-B(10 Suppl B):41-7. ©2016 Lisowski et al.

  12. Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies.

    Science.gov (United States)

    Charles-Schoeman, Christina; van der Heijde, Désirée; Burmester, Gerd R; Nash, Peter; Zerbini, Cristiano A F; Connell, Carol A; Fan, Haiyun; Kwok, Kenneth; Bananis, Eustratios; Fleischmann, Roy

    2018-02-01

    Tofacitinib has been investigated for the treatment of rheumatoid arthritis (RA) in phase III studies in which concomitant glucocorticoids (GC) were allowed. We analyzed the effect of GC use on efficacy outcomes in patients with RA receiving tofacitinib and/or methotrexate (MTX) or conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in these studies. Our posthoc analysis included data from 6 phase III studies (NCT01039688; NCT00814307; NCT00847613; NCT00853385; NCT00856544; NCT00960440). MTX-naive patients or patients with inadequate response to csDMARD or biological DMARD received tofacitinib 5 or 10 mg twice daily alone or with csDMARD, with or without concomitant GC. Patients receiving GC (≤ 10 mg/day prednisone or equivalent) before enrollment maintained a stable dose throughout. Endpoints included the American College of Rheumatology (ACR) 20/50/70 response rates, rates of Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA; CDAI ≤ 10) and remission (CDAI ≤ 2.8), and changes from baseline in CDAI, 28-joint count Disease Activity Score (DAS28-4)-erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain visual analog scale (VAS), and modified total Sharp score. Of 3200 tofacitinib-treated patients, 1258 (39.3%) received tofacitinib monotherapy and 1942 (60.7%) received tofacitinib plus csDMARD; 1767 (55.2%) received concomitant GC. ACR20/50/70 response rates, rates of CDAI LDA and remission, and improvements in CDAI, DAS28-4-ESR, HAQ-DI, and pain VAS with tofacitinib were generally similar with or without GC in monotherapy and combination therapy studies. GC use did not appear to affect radiographic progression in tofacitinib-treated MTX-naive patients. MTX plus GC appeared to inhibit radiographic progression to a numerically greater degree than MTX alone. Concomitant use of GC with tofacitinib did not appear to affect clinical or radiographic efficacy. MTX plus GC showed a

  13. PLATEAU IRIS – DIAGNOSIS AND TREATMENT

    Science.gov (United States)

    Stefan, Cornel; Iliescu, Daniela Adriana; Batras, Mehdi; Timaru, Cristina Mihaela; De Simone, Algerino

    2015-01-01

    Objectives: The objective of our study was to review the current knowledge on the diagnosis and treatment options of plateau iris configuration and syndrome. Systematic review methodology: Relevant publications on plateau iris that were published until 2014. Conclusions: Plateau iris syndrome is a form of primary angle closure glaucoma caused by a large or anteriorly positioned ciliary body that leads to mechanical obstruction of trabecular meshwork. This condition is most often found in younger patients. Plateau iris has been considered an abnormal anatomic variant of the iris that can be diagnosed on ultrasound biomicroscopy or optical coherence tomography of anterior segment. Patients with plateau iris syndrome can be recognized by the lack of response in angle opening after iridotomy. The treatment of choice in these cases is argon laser peripheral iridoplasty PMID:27373109

  14. PLATEAU IRIS--DIAGNOSIS AND TREATMENT.

    Science.gov (United States)

    Stefan, Cornel; Iliescu, Daniela Adriana; Batras, Mehdi; Timaru, Cristina Mihaela; De Simone, Algerino

    2015-01-01

    The objective of our study was to review the current knowledge on the diagnosis and treatment options of plateau iris configuration and syndrome. Relevant publications on plateau iris that were published until 2014. Plateau iris syndrome is a form of primary angle closure glaucoma caused by a large or anteriorly positioned ciliary body that leads to mechanical obstruction of trabecular meshwork. This condition is most often found in younger patients. Plateau iris has been considered an abnormal anatomic variant of the iris that can be diagnosed on ultrasound biomicroscopy or optical coherence tomography of anterior segment. Patients with plateau iris syndrome can be recognized by the lack of response in angle opening after iridotomy. The treatment of choice in these cases is argon laser peripheral iridoplasty.

  15. Randomised phase I/II study to evaluate carbon ion radiotherapy versus fractionated stereotactic radiotherapy in patients with recurrent or progressive gliomas: The CINDERELLA trial

    International Nuclear Information System (INIS)

    Combs, Stephanie E; Wick, Wolfgang; Debus, Jürgen; Burkholder, Iris; Edler, Lutz; Rieken, Stefan; Habermehl, Daniel; Jäkel, Oliver; Haberer, Thomas; Haselmann, Renate; Unterberg, Andreas

    2010-01-01

    Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cauteously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV gliomas. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons. First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective. In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy. Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival. The Cinderella trial is the first study to evaluate carbon ion

  16. Randomized phase III study comparing paclitaxel/cisplatin/ gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC intergroup study 30987

    NARCIS (Netherlands)

    J. Bellmunt (Joaquim); H. von der Maase (Hans); G.M. Mead (Graham); I. Skoneczna (I.); M. de Santis (Maria); G. Daugaard (Gedske); J. Boehle; C. Chevreau (Christine); L. Paz-Ares (Luis); L.R. Laufman (Leslie); E. Winquist (Eric); R. Raghavan (Raghu); S. Marreaud (Sandrine); S. Collette (Sandra); R. Sylvester (Richard); R. de Wit (Ronald)

    2012-01-01

    textabstractPurpose: 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.

  17. Creactive protein and interleukin-6 as markers of systemic inflammatory response and as prognostic factors for metastatic colorectal cancer. Data from the randomized phase III NORDIC-VII study

    DEFF Research Database (Denmark)

    Thomsen, M.; Kersten, C.; Sorbye, H.

    2015-01-01

    -6 (IL-6). Methods: The study was based on data from the randomized phase III NORDIC-VII study (Nordic FLOX +/cetuximab as first line treatment of mCRC). The effect of different markers of SIR, including modified Glasgow Prognostic Score (mGPS), derived Neutrophil Lymphocyte Ratio (dNLR), levels...

  18. Gemcitabine Plus Docetaxel Versus Docetaxel in Patients With Predominantly Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Randomized, Phase III Study by the Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Nielsen, Dorte L; Bjerre, Karsten D; Jakobsen, Erik H

    2011-01-01

    PURPOSE The objective of this phase III study was to compare the efficacy of gemcitabine plus docetaxel (GD) versus docetaxel in patients with advanced breast cancer. PATIENTS AND METHODS Predominantly human epidermal growth factor receptor 2 (HER2) -negative patients were randomly assigned...

  19. Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study.

    Science.gov (United States)

    Castagna, Antonella; Maggiolo, Franco; Penco, Giovanni; Wright, David; Mills, Anthony; Grossberg, Robert; Molina, Jean-Michel; Chas, Julie; Durant, Jacques; Moreno, Santiago; Doroana, Manuela; Ait-Khaled, Mounir; Huang, Jenny; Min, Sherene; Song, Ivy; Vavro, Cindy; Nichols, Garrett; Yeo, Jane M

    2014-08-01

    The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Mean change in HIV-1 RNA at day 8 was -1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574). © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  20. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer.

    Science.gov (United States)

    O'Shaughnessy, Joyce; Schwartzberg, Lee; Danso, Michael A; Miller, Kathy D; Rugo, Hope S; Neubauer, Marcus; Robert, Nicholas; Hellerstedt, Beth; Saleh, Mansoor; Richards, Paul; Specht, Jennifer M; Yardley, Denise A; Carlson, Robert W; Finn, Richard S; Charpentier, Eric; Garcia-Ribas, Ignacio; Winer, Eric P

    2014-12-01

    There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m(2) and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation. © 2014 by American Society of Clinical Oncology.

  1. Dolutegravir in Antiretroviral-Experienced Patients With Raltegravir- and/or Elvitegravir-Resistant HIV-1: 24-Week Results of the Phase III VIKING-3 Study

    Science.gov (United States)

    Castagna, Antonella; Maggiolo, Franco; Penco, Giovanni; Wright, David; Mills, Anthony; Grossberg, Robert; Molina, Jean-Michel; Chas, Julie; Durant, Jacques; Moreno, Santiago; Doroana, Manuela; Ait-Khaled, Mounir; Huang, Jenny; Min, Sherene; Song, Ivy; Vavro, Cindy; Nichols, Garrett; Yeo, Jane M.; Aberg, J.; Akil, B.; Arribas, J. R.; Baril, J.-G.; Blanco Arévalo, J. L.; Blanco Quintana, F.; Blick, G.; Boix Martínez, V.; Bouchaud, O.; Branco, T.; Bredeek, U. F.; Castro Iglesias, M.; Clumeck, N.; Conway, B.; DeJesus, E.; Delassus, J.-L.; De Truchis, P.; Di Perri, G.; Di Pietro, M.; Duggan, J.; Duvivier, C.; Elion, R.; Eron, J.; Fish, D.; Gathe, J.; Haubrich, R.; Henderson, H.; Hicks, C.; Hocqueloux, L.; Hodder, S.; Hsiao, C.-B.; Katlama, C.; Kozal, M.; Kumar, P.; Lalla-Reddy, S.; Lazzarin, A.; Leoncini, F.; Llibre, J. M.; Mansinho, K.; Morlat, P.; Mounzer, K.; Murphy, M.; Newman, C.; Nguyen, T.; Nseir, B.; Philibert, P.; Pialoux, G.; Poizot-Martin, I.; Ramgopal, M.; Richmond, G.; Salmon Ceron, D.; Sax, P.; Scarsella, A.; Sension, M.; Shalit, P.; Sighinolfi, L.; Sloan, L.; Small, C.; Stein, D.; Tashima, K.; Tebas, P.; Torti, C.; Tribble, M.; Troisvallets, D.; Tsoukas, C.; Viciana Fernández, P.; Ward, D.; Wheeler, D.; Wilkin, T.; Yeni, G.-P.; Louise Martin-Carpenter, J.; Uhlenbrauck, Gina

    2014-01-01

    Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was −1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID–based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574). PMID:24446523

  2. Worldwide time trends for symptoms of rhinitis and conjunctivitis: Phase III of the International Study of Asthma and Allergies in Childhood.

    Science.gov (United States)

    Björkstén, Bengt; Clayton, Tadd; Ellwood, Philippa; Stewart, Alistair; Strachan, David

    2008-03-01

    In Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) time trends in the prevalence of rhinoconjunctivitis symptoms were analysed. Cross-sectional questionnaire surveys with identical protocols and questionnaires were completed a mean of 7 yr apart in two age groups comprising 498,083 children. In the 13- to 14-yr age group 106 centres in 56 countries participated, and in the 6- to 7-yr age group 66 centres in 37 countries participated. A slight worldwide increase in rhinoconjunctivitis prevalence was observed, but the variations were large among the centres and there was no consistent regional pattern. Prevalence increases in the older children exceeding 1% per year were recorded in 13 centres, including 3 of 9 centres in Africa, 2 of 15 in Asia-Pacific, 1 of 8 in India, 3 of 15 in Latin America, 3 of 9 in Eastern Europe and 1 of 34 in Western and Northern Europe. Decreasing rhinoconjunctivititis prevalence of similar magnitude was only seen in four centres. The changes were less pronounced in the 6- to 7-yr-old children and only in one centre did any change exceed 1% per year. The decrease in highest prevalence rates in ISAAC Phase I suggests that the prevalence has peaked in those regions. An increase was recorded in several centres, mostly in low and mid-income countries. The increases were more pronounced in the older age group, suggesting that environmental influences on the development of allergy may not be limited to early childhood.

  3. Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

    Science.gov (United States)

    Lorusso, V; Leone, B; Di Vagno, G; Manzione, L; Palmeri, S; Vallejo, C; Machiavelli, M; Nacci, G; Bilancia, D; Leonardi, V; Catino, A; Gargano, G; Loverro, G; Selvaggi, L; De Lena, M

    1998-02-01

    Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

  4. Quality of life after radiation therapy of cerebral low-grade gliomas of the adult: results of a randomised Phase III trial on dose response (EORTC trial 22844)

    Energy Technology Data Exchange (ETDEWEB)

    Kiebert, G.M. [MEDTAP International, 27 Gilbert Street, London (United Kingdom); Curran, D. [EORTC Data Centre Brussels (Belgium); Aaronson, N.K. [The Netherlands Cancer Institute, Amsterdam (Netherlands); Bolla, M. [Centre Hospitalier Regional Universitaire, Grenoble (France); Menten, J. [University Hospital Gasthuisberg Leuven (Belgium); Rutten, E.H.J.M. [University Hospital St. Radboud, Nijmegen (Netherlands); Nordman, E. [Turku University Central Hospital, Turku (Finland); Silvestre, M.E. [Hospital Santa Maria, Lisbon (Portugal); Pierart, M. [EORTC Data Centre, Brussels (Belgium); Karim, A.B.M.F. [Free University Hospital, Amsterdam (Netherlands)

    1998-11-01

    In 1985, the EORTC Radiotherapy Co-operative Group launched a randomised phase III study comparing high-dose (59.4 Gy in 6.5 weeks) versus low-dose (45 Gy in 5 weeks) radiotherapy with conventional techniques in patients diagnosed with low-grade cerebral glioma. The primary endpoint of the study was survival. No difference in survival was observed between the two treatment strategies. A quality of life (QoL) questionnaire consisting of 47 items assessing a range of physical, psychological, social, and symptom domains was included in the trial to measure the impact of treatment over time. Patients who received high-dose radiotherapy tended to report lower levels of functioning and more symptom burden following completion of radiotherapy. These group differences were statistically significant for fatigue/malaise and insomnia immediately after radiotherapy and in leisure time and emotional functioning at 7-15 months after randomisation. These findings suggest that for conventional radiotherapy for low-grade cerebral glioma, a schedule of 45 Gy in 5 weeks not only saves valuable resources, but also spares patients a prolonged treatment at no loss of clinical efficacy. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. A Microfabricated Segmented-Involute-Foil Regenerator for Enhancing Reliability and Performance of Stirling Engines. Phase III Final Report for the Radioisotope Power Conversion Technology NRA

    Science.gov (United States)

    Ibrahim, Mounir B.; Gedeon, David; Wood, Gary; McLean, Jeffrey

    2009-01-01

    Under Phase III of NASA Research Announcement contract NAS3-03124, a prototype nickel segmented-involute-foil regenerator was microfabricated and tested in a Sunpower Frequency-Test-Bed (FTB) Stirling convertor. The team for this effort consisted of Cleveland State University, Gedeon Associates, Sunpower Inc. and International Mezzo Technologies. Testing in the FTB convertor produced about the same efficiency as testing with the original random-fiber regenerator. But the high thermal conductivity of the prototype nickel regenerator was responsible for a significant performance degradation. An efficiency improvement (by a 1.04 factor, according to computer predictions) could have been achieved if the regenerator was made from a low-conductivity material. Also, the FTB convertor was not reoptimized to take full advantage of the microfabricated regenerator s low flow resistance; thus, the efficiency would likely have been even higher had the FTB been completely reoptimized. This report discusses the regenerator microfabrication process, testing of the regenerator in the Stirling FTB convertor, and the supporting analysis. Results of the pre-test computational fluid dynamics (CFD) modeling of the effects of the regenerator-test-configuration diffusers (located at each end of the regenerator) are included. The report also includes recommendations for further development of involute-foil regenerators from a higher-temperature material than nickel.

  6. Beating the odds: Successful establishment of a Phase II/III clinical research trial in resource-poor Liberia during the largest-ever Ebola outbreak

    Directory of Open Access Journals (Sweden)

    J. Doe-Anderson

    2016-12-01

    Full Text Available It has been argued that a country such as Liberia, not fully recovered from the devastation of decades of civil unrest, lacked the appropriate ethical and regulatory framework, basic human and health care services, and infrastructure to carry out clinical trials according to international standards of quality during a public health emergency. However, as Liberia, Sierra Leone, and Guinea were being ravaged by the largest and most devastating Ebola Virus Disease (EVD outbreak ever recorded, the topic of conducting clinical trials of experimental vaccine and treatment candidates in these resource-poor countries generated the keen interest and concern of scientists, researchers, physicians, bioethicists, philanthropists, and even politicians. Decisive action on behalf of the Liberian government, and a timely positive and supportive response from the United States (U.S. government, led to the formation of PREVAIL (Partnership for Research on Ebola Vaccines in Liberia – a clinical research partnership between the two governments. Within a span of 12 weeks, this partnership accomplished the unimaginable: the successful initiation of a Phase II/III vaccine clinical trial for EVD in Liberia. This paper will discuss the dynamics of the research collaboration, barriers encountered, breakthroughs realized, key elements of success, and lessons learned in the process.

  7. Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation

    International Nuclear Information System (INIS)

    Antunes, Heliton S.; Herchenhorn, Daniel; Small, Isabele A.; Araújo, Carlos M.M.; Viégas, Celia Maria Pais; Cabral, Elida; Rampini, Mariana P.; Rodrigues, Pedro C.; Silva, Tereza G.P.; Ferreira, Elza M.S.; Dias, Fernando L.; Ferreira, Carlos G.

    2013-01-01

    Background: Oral mucositis (OM) is a complication of chemoradiotherapy treatment of head and neck squamous cell carcinoma (HNSCC) patients with no effective therapy. This study was designed to assess the efficacy of preventive low-level laser therapy (LLLT) in reducing the incidence of grade 3–4 OM. Material and methods: From June 2007 to December 2010, 94 HNSCC patients entered a prospective, randomized, double-blind, placebo-controlled phase III trial. Chemoradiotherapy consisted of conventional radiotherapy plus concurrent cisplatin every 3 weeks. A diode InGaAlP (660 nm–100 mW–1 J–4 J/cm 2 ) was used. OM evaluation was performed by WHO and OMAS scales and quality of life by EORTC questionnaires (QLQ). Results: A six-fold decrease in the incidence of grades 3–4 OM was detected in the LLLT group compared to the placebo; (6.4% versus 40.5%). LLLT impacted the incidence of grades 3–4 OM to a relative risk ratio of 0.158 (CI 95% 0.050–0.498). After treatment QLQ-C30 showed, differences favoring LLLT in physical, emotional functioning, fatigue, and pain; while the QLQ-H and N35 showed improvements in LLLT arm for pain, swallowing, and trouble with social eating. Conclusion: Preventive LLLT in HNSCC patients receiving chemoradiotherapy is an effective tool for reducing the incidence of grade 3–4 OM. Efficacy data were corroborated by improvements seen in quality of life

  8. Efficacy and safety of human papillomavirus vaccine for primary prevention of cervical cancer: A review of evidence from phase III trials and national programs

    Directory of Open Access Journals (Sweden)

    Partha Basu

    2013-01-01

    Full Text Available The Human Papillomavirus (HPV vaccines have been widely introduced in the national immunization programs in most of the medium and high income countries following endorsement from national and international advisory bodies. HPV vaccine is unique and its introduction is challenging in many ways - it is the first vaccine developed to prevent any cancer, the vaccine is gender specific, it targets adolescent females who are difficult to reach by any health intervention programs. It is not unusual for such a vaccine to face scepticism and reservations not only from lay public but also from professionals in spite of the clinical trial results convincingly and consistently proving their efficacy and safety. Over the last few years millions of doses of the HPV vaccine have been administered round the world and the efficacy and safety data have started coming from the real life programs. A comprehensive cervical cancer control program involving HPV vaccination of the adolescent girls and screening of the adult women has been proved to be the most cost-effective approach to reduce the burden of cervical cancer. The present article discusses the justification of HPV vaccination in the backdrop of natural history of cervical cancer, the mechanism of action of the vaccines, efficacy and safety data from phase III randomized controlled trials as well as from the national immunization programs of various countries.

  9. Comparison of geochemical data obtained using four brine sampling methods at the SECARB Phase III Anthropogenic Test CO2 injection site, Citronelle Oil Field, Alabama

    Science.gov (United States)

    Conaway, Christopher; Thordsen, James J.; Manning, Michael A.; Cook, Paul J.; Trautz, Robert C.; Thomas, Burt; Kharaka, Yousif K.

    2016-01-01

    The chemical composition of formation water and associated gases from the lower Cretaceous Paluxy Formation was determined using four different sampling methods at a characterization well in the Citronelle Oil Field, Alabama, as part of the Southeast Regional Carbon Sequestration Partnership (SECARB) Phase III Anthropogenic Test, which is an integrated carbon capture and storage project. In this study, formation water and gas samples were obtained from well D-9-8 #2 at Citronelle using gas lift, electric submersible pump, U-tube, and a downhole vacuum sampler (VS) and subjected to both field and laboratory analyses. Field chemical analyses included electrical conductivity, dissolved sulfide concentration, alkalinity, and pH; laboratory analyses included major, minor and trace elements, dissolved carbon, volatile fatty acids, free and dissolved gas species. The formation water obtained from this well is a Na–Ca–Cl-type brine with a salinity of about 200,000 mg/L total dissolved solids. Differences were evident between sampling methodologies, particularly in pH, Fe and alkalinity. There was little gas in samples, and gas composition results were strongly influenced by sampling methods. The results of the comparison demonstrate the difficulty and importance of preserving volatile analytes in samples, with the VS and U-tube system performing most favorably in this aspect.

  10. Efficacy of S-flurbiprofen plaster in knee osteoarthritis treatment: Results from a phase III, randomized, active-controlled, adequate, and well-controlled trial.

    Science.gov (United States)

    Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Matsumoto, Hideo; Hoshino, Yuichi

    2017-01-01

    S-flurbiprofen plaster (SFPP) is a novel non-steroidal anti-inflammatory drug (NSAID) patch, intended for topical treatment for musculoskeletal diseases. This trial was conducted to examine the effectiveness of SFPP using active comparator, flurbiprofen (FP) patch, on knee osteoarthritis (OA) symptoms. This was a phase III, multi-center, randomized, adequate, and well-controlled trial, both investigators and patients were blinded to the assigned treatment. Enrolled 633 knee OA patients were treated with either SFPP or FP patch for two weeks. The primary endpoint was improvement in knee pain on rising from the chair as assessed by visual analogue scale (rVAS). Safety was evaluated through adverse events (AEs). The change in rVAS was 40.9 mm in SFPP group and 30.6 mm in FP patch group (p < 0.001). The incidence of drug-related AEs at the application site was 9.5% (32 AEs, 29 mild and 3 moderate) in SFPP and 1.6% in FP patch (p < 0.001). Withdrawals due to AE were five in SFPP and one in FP patch. The superiority of SFPP in efficacy was demonstrated. Most of AEs were mild and few AEs led to treatment discontinuation. Therefore, SFPP provides an additional option for knee OA therapy.

  11. Results in the elderly with locally advanced rectal cancer from the ACCOR12/PRODIGE 2 phase III trial: Tolerance and efficacy

    International Nuclear Information System (INIS)

    François, Eric; Azria, David; Gourgou-Bourgade, Sophie; Jarlier, Marta; Martel-Laffay, Isabelle; Hennequin, Christophe; Etienne, Pierre-Luc;