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Sample records for groundwater phase iii

  1. Underground Test Area Subproject Phase I Data Analysis Task. Volume III - Groundwater Recharge and Discharge Data Documentation Package

    Energy Technology Data Exchange (ETDEWEB)

    None

    1996-10-01

    Volume III of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the data covering groundwater recharge and discharge. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  2. 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

  3. 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

  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. 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)] (eds.)

    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.)

  6. Advanced Emissions Control Development Program: Phase III

    Energy Technology Data Exchange (ETDEWEB)

    G.T. Amrhein; R.T. Bailey; W. Downs; M.J. Holmes; G.A. Kudlac; D.A. Madden

    1999-07-01

    The primary objective of the Advanced Emissions Control Development Program (AECDP) is to develop practical, cost-effective strategies for reducing the emissions of air toxics from coal-fired boilers. The project goal is to effectively control air toxic emissions through the use of conventional flue gas clean-up equipment such as electrostatic precipitators (ESPs), fabric filters (baghouses - BH), and wet flue gas desulfurization systems (WFGD). Development work concentrated on the capture of trace metals, fine particulate, hydrogen chloride and hydrogen fluoride, with an emphasis on the control of mercury. The AECDP project is jointly funded by the US Department of Energy's Federal Energy Technology Center (DOE), the Ohio Coal Development Office within the Ohio Department of Development (OCDO), and Babcock and Wilcox, a McDermott company (B and W). This report discusses results of all three phases of the AECDP project with an emphasis on Phase III activities. Following the construction and evaluation of a representative air toxics test facility in Phase I, Phase II focused on characterization of the emissions of mercury and other air toxics and the control of these emissions for typical operating conditions of conventional flue gas clean-up equipment. Some general comments that can be made about the control of air toxics while burning a high-sulfur bituminous coal are as follows: (1) particulate control devices such as ESP's and baghouses do a good job of removing non-volatile trace metals, (2) particulate control devices (ESPs and baghouses) effectively remove the particulate-phase mercury, but the particulate-phase mercury was only a small fraction of the total for the coals tested, (3) wet scrubbing can effectively remove hydrogen chloride and hydrogen fluoride, and (4) wet scrubbers show good potential for the removal of mercury when operated under certain conditions, however, for certain applications, system enhancements can be required to achieve

  7. The oxidation of As(III) in groundwater using biological manganese removal filtration columns.

    Science.gov (United States)

    Yang, Hong; Sun, Wenyong; Ge, Huoqing; Yao, Renda

    2015-01-01

    Arsenic is known as a toxic element to humans, and has been reported to co-exist with iron and manganese in groundwater worldwide. The typical method for arsenic removal from groundwater is to oxidize trivalent (As(III)) to pentavalent (As(V)) followed by the As(V) removal. This study aims to evaluate the oxidization efficiency of As(III) in a mature biological manganese (Mn(2+)) removal filtration system with different elevated influent As(III) concentrations. The effects of influent Mn(2+) concentrations, influent As(III) concentrations, filtration rates and dissolved oxygen (DO) levels on the efficiency of As(III) oxidation were assessed. The results showed that As(III) oxidation can be simultaneously achieved with removing Mn(2+) in the filtration system. The oxidation efficiency was not impacted by increasing the influent As(III) concentration up to nearly 2500 µg L(-1), but the filtration rate was limited at 11 m h(-1) for maintaining the effluent As(III) concentration below 10 µg L(-1). The oxidation process followed first-order kinetics with the constant reaching 0.56-0.61 min(-1). The As(III) oxidation process was most likely to be mediated by the bacterial community initially developed for Mn(2+) removal in the filtration system, which performed the catalytic oxidation for As(III).

  8. As(III) oxidation by MnO2 during groundwater treatment.

    Science.gov (United States)

    Gude, J C J; Rietveld, L C; van Halem, D

    2017-03-15

    The top layer of natural rapid sand filtration was found to effectively oxidise arsenite (As(III)) in groundwater treatment. However, the oxidation pathway has not yet been identified. The aim of this study was to investigate whether naturally formed manganese oxide (MnO2), present on filter grains, could abiotically be responsible for As(III) oxidation in the top of a rapid sand filter. For this purpose As(III) oxidation with two MnO2 containing powders was investigated in aerobic water containing manganese(II) (Mn(II)), iron(II) (Fe(II)) and/or iron(III) (Fe(III)). The first MnO2 powder was a very pure - commercially available - natural MnO2 powder. The second originated from a filter sand coating, produced over 22 years in a rapid filter during aeration and filtration. Jar test experiments showed that both powders oxidised As(III). However, when applying the MnO2 in aerated, raw groundwater, As(III) removal was not enhanced compared to aeration alone. It was found that the presence of Fe(II)) and Mn(II) inhibited As(III) oxidation, as Fe(II) and Mn(II) adsorption and oxidation were preferred over As(III) on the MnO2 surface (at pH 7). Therefore it is concluded that just because MnO2 is present in a filter bed, it does not necessarily mean that MnO2 will be available to oxidise As(III). However, unlike Fe(II), the addition of Fe(III) did not hinder As(III) oxidation on the MnO2 surface; resulting in subsequent effective As(V) removal by the flocculating hydrous ferric oxides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. 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

  10. Questa Baseline and Pre-Mining Ground-Water Quality Investigation 15.-Methods of Phase II and III Well Installation and Development and Results of Well Logging, Hydraulic Testing, and Water-Level Measurements in the Red River Valley, New Mexico, 2002-04

    Science.gov (United States)

    Blanchard, Paul J.; Bartolino, James R.; Donohoe, Lisa C.; McAda, Douglas P.; Naus, Cheryl A.; Morin, Roger H.

    2007-01-01

    In April 2001, the U.S. Geological Survey and the New Mexico Environment Department began a cooperative study to infer the pre-mining ground-water chemistry at the Molycorp molybdenum mine site in the Red River Valley of north- central New Mexico. This report is one in a series of reports that can be used to determine pre-mining ground-water conditions at the mine site. Weathering of hydrothermally altered bedrock in the study area has resulted in steep, highly erosive, and sparsely vegetated scar areas that are clearly visible from the ground and in aerial photographs. Runoff from intense summer rainfall over tributary drainages containing scar areas can transport large quantities of sediment and form debris fans where these tributaries join the Red River. Twenty-nine observation wells were installed in three phases as part of this study in the Red River Valley and tributary drainages. Eight Phase II observation wells were drilled using an air-rotary/hammer rig. Three Phase II and 10 phase III small-diameter wells were installed using a direct-push rig. Lithologic logs were recorded for all eight Phase II drilled wells. Borehole geophysical logging (including natural gamma, induction, and single-detector neutron) was conducted in three Phase II wells. Aquifer tests conducted during 2003 to estimate the hydraulic properties of debris-flow and Red River alluvial deposits in and near Straight Creek included a flow-meter survey, slug tests, and a pumping test. Results of a flow-meter survey in well SC-7A indicated that about 77 percent of the water entered the well from a 10-foot-thick zone near the top of the screened interval and about 23 percent of the water entered the well from a 15-foot-thick zone near the bottom of the screened interval. Slug tests, performed in 11 wells during June 3-5, 2003, indicated that the mean and median estimated hydraulic conductivities for debris-flow deposits were 15.25 and 15.35 feet per day, respectively, for bedrock were 0.12 and

  11. Groundwater flow modelling of the excavation and operational phases - Laxemar

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Urban (Computer-aided Fluid Engineering AB, Lyckeby (Sweden)); Rhen, Ingvar (SWECO Environment AB, Falun (Sweden))

    2010-12-15

    As a part of the license application for a final repository for spent nuclear fuel at Forsmark, the Swedish Nuclear Fuel and Waste Management Company (SKB) has undertaken a series of groundwater flow modelling studies. These represent time periods with different hydraulic conditions and the simulations carried out contribute to the overall evaluation of the repository design and long-term radiological safety. The modelling study reported here presents calculated inflow rates, drawdown of the groundwater table and upconing of deep saline water for different levels of grouting efficiency during the excavation and operational phases of a final repository at Laxemar. The inflow calculations were accompanied by a sensitivity study, which among other matters handled the impact of different deposition hole rejection criteria. The report also presents tentative modelling results for the duration of the saturation phase, which starts once the used parts of the repository are being backfilled

  12. Characterization of Co(III) EDTA-Reducing Bacteria in Metal- and Radionuclide-Contaminated Groundwater

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Weimin [Arizona State University; Gentry, Terry J [ORNL; Mehlhorn, Tonia L [ORNL; Carroll, Sue L [ORNL; Jardine, Philip M [ORNL; Zhou, Jizhong [University of Oklahoma, Norman

    2010-01-01

    The Waste Area Grouping 5 (WAG5) site at Oak Ridge National Laboratory has a potential to be a field site for evaluating the effectiveness of various bioremediation approaches and strategies. The site has been well studied in terms of its geological and geochemical properties over the past decade. However, despite the importance of microorganisms in bioremediation processes, the microbiological populations at the WAG5 site and their potential in bioremediation have not been similarly evaluated. In this study, we initiated research to characterize the microbial populations in WAG5 groundwater. Approximately 100 isolates from WAG5 groundwater were isolated and selected based on colony morphology. Fifty-five unique isolates were identified by BOX-PCR and subjected to further characterization. 16S rRNA sequences indicated that these isolates belong to seventeen bacterial genera including Alcaligenes (1 isolate), Aquamonas (1), Aquaspirillum (1), Bacillus (10), Brevundimonas (5), Caulobacter (7), Dechloromonas (2), Janibacter (1), Janthinobacterium (2), Lactobacillus (1), Paenibacillus (4), Pseudomonas (9), Rhodoferax (1), Sphingomonas (1), Stenotrophomonas (6), Variovorax (2), and Zoogloea (1). Metal respiration assays identified several isolates, which phylogenically belong or are close to Caulobacter, Stenotrophomonas, Bacillus, Paenibacillus and Pseudomonas, capable of reducing Co(III)EDTA- to Co(II)EDTA{sup 2-} using the defined M1 medium under anaerobic conditions. In addition, using WAG5 groundwater directly as the inoculants, we found that organisms associated with WAG5 groundwater can reduce both Fe(III) and Co(III) under anaerobic conditions. Further assays were then performed to determine the optimal conditions for Co(III) reduction. These assays indicated that addition of various electron donors including ethanol, lactate, methanol, pyruvate, and acetate resulted in metal reduction. These experiments will provide useful background information for future

  13. Utility-based optimization of phase II/III programs.

    Science.gov (United States)

    Kirchner, Marietta; Kieser, Meinhard; Götte, Heiko; Schüler, Armin

    2016-01-30

    Phase II and phase III trials play a crucial role in drug development programs. They are costly and time consuming and, because of high failure rates in late development stages, at the same time risky investments. Commonly, sample size calculation of phase III is based on the treatment effect observed in phase II. Therefore, planning of phases II and III can be linked. The performance of the phase II/III program crucially depends on the allocation of the resources to phases II and III by appropriate choice of the sample size and the rule applied to decide whether to stop the program after phase II or to proceed. We present methods for a program-wise phase II/III planning that aim at determining optimal phase II sample sizes and go/no-go decisions in a time-to-event setting. Optimization is based on a utility function that takes into account (fixed and variable) costs of the drug development program and potential gains after successful launch. The proposed methods are illustrated by application to a variety of scenarios typically met in oncology drug development.

  14. Industrial fuel gas demonstration plant program. Current working estimate. Phase III and III

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    The United States Department of Energy (DOE) executed a contract with Memphis Light, Gas and Water Division (MLGW) which requires MLGW to perform process analysis, design, procurement, construction, testing, operation, and evaluation of a plant which will demonstrate the feasibility of converting high sulfur bituminous coal to industrial fuel gas with a heating value of 300 +- 30 Btu per standard cubic foot (SCF). The demonstration plant is based on the U-Gas process, and its product gas is to be used in commercial applications in Memphis, Tenn. The contract specifies that the work is to be conducted in three phases. The Phases are: Phase I - Program Development and Conceptual Design; Phase II - Demonstration Plant Final Design, Procurement and Construction; and Phase III - Demonstration Plant Operation. Under Task III of Phase I, a Cost Estimate for the Demonstration Plant was completed as well as estimates for other Phase II and III work. The output of this Estimate is presented in this volume. This Current Working Estimate for Phases II and III is based on the Process and Mechanical Designs presented in the Task II report (second issue) and the 12 volumes of the Task III report. In addition, the capital cost estimate summarized in the appendix has been used in the Economic Analysis (Task III) Report.

  15. Groundwater.

    Science.gov (United States)

    Braids, Olin C.; Gillies, Nola P.

    1978-01-01

    Presents a literature review of groundwater quality covering publications of 1977. This review includes: (1) sources of groundwater contamination; and (2) management of groundwater. A list of 59 references is also presented. (HM)

  16. Oxford phase III meniscal bearing fracture: case report.

    Science.gov (United States)

    Lim, Hong-Chul; Shon, Won-Yong; Kim, Seung-Ju; Bae, Ji-Hoon

    2014-01-01

    Meniscal bearing fracture is a rare complication of phase III Oxford unicompartmental knee replacement (UKR). We report a case of a meniscal bearing fracture that occurred 7 years after phase III Oxford medial UKR. The meniscal bearing showed uneven delamination of the polyethylene in the thinnest articular surface and an impingement lesion. This lesion initiated a fatigue crack that propagated to cause failure of the meniscal bearing. This is the first report of a meniscal bearing fracture without a posterior marker wire.

  17. Using phase II data for the analysis of phase III studies: An application in rare diseases.

    Science.gov (United States)

    Wandel, Simon; Neuenschwander, Beat; Röver, Christian; Friede, Tim

    2017-06-01

    Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R.

  18. Groundwater flow modelling of the excavation and operational phases - Forsmark

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Urban (Computer-aided Fluid Engineering AB, Lyckeby (Sweden)); Follin, Sven (SF GeoLogic AB, Taeby (Sweden))

    2010-07-15

    As a part of the license application for a final repository for spent nuclear fuel at Forsmark, the Swedish Nuclear Fuel and Waste Management Company (SKB) has undertaken a series of groundwater flow modelling studies. These represent time periods with different climate conditions and the simulations carried out contribute to the overall evaluation of the repository design and long-term radiological safety. The modelling study reported here presents calculated inflow rates, drawdown of the groundwater table and upconing of deep saline water for different levels of grouting efficiency during the excavation and operational phases of a final repository at Forsmark. The inflow calculations are accompanied by a sensitivity study, which among other matters handles the impact of parameter heterogeneity, different deposition hole rejection criteria, and the SFR facility (the repository for short-lived radioactive waste located approximately 1 km to the north of the investigated candidate area for a final repository at Forsmark). The report also presents tentative modelling results for the duration of the saturation phase, which starts once the used parts of the repository are being backfilled.

  19. Using phase II data for the analysis of phase III studies: an application in rare diseases

    OpenAIRE

    Wandel, Simon; Neuenschwander, Beat; Friede, Tim; Röver, Christian

    2016-01-01

    Clinical research and drug development in orphan diseases is challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncer...

  20. 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.

  1. High Voltage, Low Inductance Hydrogen Thyratron Study Program, Phase III.

    Science.gov (United States)

    1981-12-01

    results and supporting information that bear on the progress of the Program as a whole. The Government’s Contract Monitor for Phase III was Mr. William ...ST ATTN: DRDEL-LL; -SB; -AP (IN TURN) I DRSEL-MA-MP 2800 Powder Mill Road 2 DRSEL-PA Adelphi, MD 20783 001 CINDAS 001 Cdr, ERADCOM Purdue Industrial

  2. CHAOS III: Gas-phase Abundances in NGC 5457

    Science.gov (United States)

    Croxall, Kevin V.; Pogge, Richard W.; Berg, Danielle A.; Skillman, Evan D.; Moustakas, John

    2016-10-01

    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.

  3. Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility

    OpenAIRE

    Kimani, Peter K.; Todd, Susan; Stallard, Nigel

    2013-01-01

    Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point esti...

  4. Treatment of groundwater containing Mn(II), Fe(II), As(III) and Sb(III) by bioaugmented quartz-sand filters.

    Science.gov (United States)

    Bai, Yaohui; Chang, Yangyang; Liang, Jinsong; Chen, Chen; Qu, Jiuhui

    2016-12-01

    High concentrations of iron (Fe(II)) and manganese (Mn(II)) often occur simultaneously in groundwater. Previously, we demonstrated that Fe(II) and Mn(II) could be oxidized to biogenic Fe-Mn oxides (BFMO) via aeration and microbial oxidation, and the formed BFMO could further oxidize and adsorb other pollutants (e.g., arsenic (As(III)) and antimony (Sb(III))). To apply this finding to groundwater remediation, we established four quartz-sand columns for treating groundwater containing Fe(II), Mn(II), As(III), and Sb(III). A Mn-oxidizing bacterium (Pseudomonas sp. QJX-1) was inoculated into two parallel bioaugmented columns. Long-term treatment (120 d) showed that bioaugmentation accelerated the formation of Fe-Mn oxides, resulting in an increase in As and Sb removal. The bioaugmented columns also exhibited higher overall treatment effect and anti-shock load capacity than that of the non-bioaugmented columns. To clarify the causal relationship between the microbial community and treatment effect, we compared the biomass of active bacteria (reverse-transcribed real-time PCR), bacterial community composition (Miseq 16S rRNA sequencing) and community function (metagenomic sequencing) between the bioaugmented and non-bioaugmented columns. Results indicated that the QJX1 strain grew steadily and attached onto the filter material surface in the bioaugmented columns. In general, the inoculated strain did not significantly alter the composition of the indigenous bacterial community, but did improve the relative abundances of xenobiotic metabolism genes and Mn oxidation gene. Thus, bioaugmentation intensified microbial degradation/utilization for the direct removal of pollutants and increased the formation of Fe-Mn oxides for the indirect removal of pollutants. Our study provides an alternative method for the treatment of groundwater containing high Fe(II), Mn(II) and As/Sb. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Advanced Stirling Converter (ASC) Phase III Progress Update

    Science.gov (United States)

    Wood, J. Gary; Wilson, Kyle; Buffalino, Andrew; Frye, Patrick; Matejczyk, Dan; Penswick, L. B.

    2007-01-01

    Progress in the development of the Advanced Stirling Convertor (ASC) is presented here. The ASC is being developed under contact with the NASA Glenn Research Center and is supported by the Science Mission Directorate for potential use in future radioisotope power systems having significantly increased efficiency and higher specific power compared to the current thermoelectric systems. Phase II of the effort successfully demonstrated very high conversion efficiency and also demonstrated the low mass capability of the ASC design. The non-hermetic ASC-1 converters demonstrated during Phase II employ superalloy heater heads designed for greater than 14 years life at 850 °C operation. Phase III, which is reported on here, includes the fabrication of multiple next generation hermetic ASC-2 units. Phase III also includes the development of multiple lower-temperature (650 °C hot end) convertors based on the basic ASC design and designated as ASC-0 units. Multiple converters are being built for extended life testing at NASA GRC.

  6. 77 FR 40936 - 60-Day Notice of Proposed Information Collection: Passport Demand Forecasting Study Phase III

    Science.gov (United States)

    2012-07-11

    ...: Passport Demand Forecasting Study Phase III. OMB Control Number: None. Type of Request: Reinstatement of a... Notice of Proposed Information Collection: Passport Demand Forecasting Study Phase III ACTION: Notice of.... The data gathered from the Passport Demand Forecasting Study Phase III will be used to monitor, assess...

  7. Computational Analysis of the SRS Phase III Salt Disposition Alternatives

    Energy Technology Data Exchange (ETDEWEB)

    Dimenna, R.A.

    1999-10-07

    Completion of the Phase III evaluation and comparison of salt disposition alternatives was supported with enhanced computer models and analysis for each case on the ''short list'' of four options. SPEEDUP(TM) models and special purpose models describing mass and energy balances and flow rates were developed and used to predict performance and production characteristics for each of the options. Results from the computational analysis were a key part of the input used to select a primary and an alternate salt disposition alternative.

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

    Science.gov (United States)

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

    2017-02-23

    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.

  9. Inability of positive phase II clinical trials of investigational treatments to subsequently predict positive phase III clinical trials in glioblastoma.

    Science.gov (United States)

    Mandel, Jacob J; Yust-Katz, Shlomit; Patel, Akash J; Cachia, David; Liu, Diane; Park, Minjeong; Yuan, Ying; A Kent, Thomas; de Groot, John F

    2017-07-31

    Glioblastoma is the most common primary malignant brain tumor in adults, but effective therapies are lacking. With the scarcity of positive phase III trials, which are increasing in cost, we examined the ability of positive phase II trials to predict statistically significant improvement in clinical outcomes of phase III trials. A PubMed search was conducted to identify phase III clinical trials performed in the past 25 years for patients with newly diagnosed or recurrent glioblastoma. Trials were excluded if they did not examine an investigational chemotherapy or agent, if they were stopped early owing to toxicity, if they lacked prior phase II studies, or if a prior phase II study was negative. Seven phase III clinical trials in newly diagnosed glioblastoma and 4 phase III clinical trials in recurrent glioblastoma met the inclusion criteria. Only 1 (9%) phase III study documented an improvement in overall survival and changed the standard of care. The high failure rate of phase III trials demonstrates the urgent need to increase the reliability of phase II trials of treatments for glioblastoma. Strategies such as the use of adaptive trial designs, Bayesian statistics, biomarkers, volumetric imaging, and mathematical modeling warrant testing. Additionally, it is critical to increase our expectations of phase II trials so that positive findings increase the probability that a phase III trial will be successful.

  10. 1999 Annual Mixed Waste Management Facility Groundwater Correction - Action Report (Volumes I, II, and III)

    Energy Technology Data Exchange (ETDEWEB)

    Chase, J.

    2000-06-14

    This Corrective Action Report (CAR) for the Mixed Waste Management Facility (MWMF) is being prepared to comply with the Resource Conservation and Recovery Act (RCRA) Permit Number SC1 890 008 989, dated October 31, 1999. This CAR compiles and presents all groundwater sampling and monitoring activities that are conducted at the MWMF. As set forth in previous agreements with South Carolina Department of Health and Environmental Control (SCDHEC), all groundwater associated with the Burial Ground Complex (BGC) (comprised of the MWMF, Low-Level Radioactive Waste Disposal Facility, and Old Radioactive Waste Burial Ground) will be addressed under this RCRA Permit. This CAR is the first to be written for the MWMF and presents monitoring activities and results as an outcome of Interim Status and limited Permitted Status activities. All 1999 groundwater monitoring activities were conducted while the MWMF was operated during Interim Status. Changes to the groundwater monitoring program were made upon receipt of the RCRA Permit, where feasible. During 1999, 152 single-screened and six multi-screened groundwater monitoring wells at the BGC monitored groundwater quality in the uppermost aquifer as required by the South Carolina Hazardous Waste Management Regulations (SCHWMR), settlement agreements 87-52-SW and 91-51-SW, and RCRA Permit SC1 890 008 989. However, overall compliance with the recently issued RCRA Permit could not be implemented until the year 2000 due to the effective date of the RCRA Permit and scheduling of groundwater monitoring activities. Changes have been made to the groundwater monitoring network to meet Permit requirements for all 2000 sampling events.

  11. Phase III ResonantSonic{reg_sign} report

    Energy Technology Data Exchange (ETDEWEB)

    Newcomer, D.R. [comp.; Last, G.V.; Friley, J.R.; Strope, L.A.; Johnston, B.V.

    1996-09-01

    The ResonantSonic drilling system was tested at the hanford Site in the fiscal year 1991-1992 under the auspices of the Drilling Technology Development Program and the Environmental Restoration Program. The purpose of that program was to develop, test, and demonstrate drilling methods that are environmentally acceptable, safe, efficient, and cost effective when drilling and sampling in hazardous and radioactive waste sites. The cable-tool method has historically been the primary drilling method employed for characterization and remediation projects at the Hanford site. The cable-tool method can be used reliably in a wide variety of geologic conditions and yields continuous, relatively intact core samples. however, the disadvantages of this method are that the penetration rates are slow relative to most other drilling techniques. This report represents the completion of the ResonantSonic drilling program test activities. A brief description of the ResonantSonic drilling program is given. Phases I and II activities are also presented. Phase III activities are outlined. The conclusions drawn from the results and recommendations for further work to improve the drilling technology are discussed.

  12. 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...

  13. 2-Phase groundwater and soil vapor extraction site test at McClellan AFB

    Energy Technology Data Exchange (ETDEWEB)

    Koerner, C.; Kingsley, G.B.; Lawrence J. [Radian Corp., Sacramento, CA (United States)] [and others

    1995-09-01

    The innovative 2-phase extraction technique is a method recently patented by Xerox Corporation for simultaneously extracting contaminated groundwater and soil vapor from the subsurface. The 2-phase technique is primarily applicable to those sites with semipermeable soils containing volatile organic compound (VOC) contamination in both soils and groundwater. This technique has several distinct advantages over either conventional soil vapor extraction or groundwater extraction, because it can: cut the dollar per-contaminant-pound cleanup costs by an order of magnitude; simplify the extraction and treatment of both contaminated water and vapor; and shorten remediation times. The U.S. EPA and the Air Force elected to conduct an EPA Site test of the 2-phase Extraction technology at McClellan results indicate: The groundwater flow rate is twice that of the pump-and-treat system. The mass of contaminants from a single well removed increased from 130 lbs/year to more than 5,000 lbs/year, over 30 times more than the pump-and treat rate, with potential for even higher removal rates: 5,000 to 8,000 pounds of contaminants per year. Up to 95% of the contamination was extracted in the vapor phase, where it could be treated more easily and efficiently.

  14. Final report : Phase III targeted investigation, Everest, Kansas.

    Energy Technology Data Exchange (ETDEWEB)

    LaFreniere, L. M.; Environmental Science Division

    2006-01-31

    The Commodity Credit Corporation (CCC), an agency of the U.S. Department of Agriculture (USDA), formerly operated grain storage facilities at two different locations at Everest, Kansas (Figure 1.1). One facility (referred to in this report as the Everest facility) was at the western edge of the city. The second facility (referred to in this report as Everest East) was about 0.5 mi northeast of the town. The CCC/USDA operated these facilities from the early 1950s until the early 1970s, at a time when commercial fumigants containing carbon tetrachloride were in common use by the CCC/USDA and private industry for the preservation of grain in storage. In 1997 the Kansas Department of Health and Environment (KDHE) sampled several domestic drinking water and non-drinking water wells in the Everest area as part of the CCC/USDA Private Well Sampling Program. All of the sampled wells were outside the Everest city limits. Carbon tetrachloride contamination was identified at a single domestic drinking water well (the Nigh well, DW06; Figure 1.1) approximately 3/8 mi northwest of the former Everest CCC/USDA grain storage facility. Subsequent KDHE investigations suggested that the contamination in DW06 could be linked to the former use of grain fumigants at the CCC/USDA facility. For this reason, the CCC/USDA is conducting a phased environmental study to determine the source and extent of the carbon tetrachloride contamination at Everest and to identify potential remedial options. The studies are being performed by the Environmental Research Division of Argonne National Laboratory. Two phases of investigation were completed previously; this report presents the findings of the targeted Phase III investigation at Everest.

  15. Monticello Mill Tailings Site Operable Unit III Annual Groundwater Report May 2014 Through April 2015, October 2015

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Jason [USDOE Office of Legacy Management, Washington, DC (United States); Smith, Fred [Navarro Research and Engineering, Inc., Oak Ridge, TN (United States)

    2015-10-01

    This report provides the annual analysis of water quality restoration progress, cumulative through April 2015, for Operable Unit (OU) III, surface water and groundwater, of the U.S. Department of Energy (DOE) Office of Legacy Management Monticello Mill Tailings Site (MMTS). The MMTS is a Comprehensive Environmental Response, Compensation, and Liability Act National Priorities List site located in and near the city of Monticello, San Juan County, Utah. MMTS comprises the 110-acre site of a former uranium- and vanadium-ore-processing mill (mill site) and 1,700 acres of surrounding private and municipal property. Milling operations generated 2.5 million cubic yards of waste (tailings) from 1942 to 1960. The tailings were impounded at four locations on the mill site. Inorganic constituents in the tailings drained from the impoundments to contaminate local surface water (Montezuma Creek) and groundwater in the underlying alluvial aquifer. Mill tailings dispersed by wind and water also contaminated properties surrounding and downstream of the mill site. Remedial actions to remove and isolate radiologically contaminated soil, sediment, and debris from the former mill site (OU I) and surrounding properties (OU II) were completed in 1999 with the encapsulation of the wastes in an engineered repository located on DOE property 1 mile south of the former mill site. Contamination of groundwater and surface water remains within OU III at levels that exceed water quality protection standards. Uranium is the primary contaminant of concern. LM implemented monitored natural attenuation with institutional controls as the OU III remedy in 2004. Because groundwater restoration proceeded more slowly than expected and did not meet performance criteria established in the OU III Record of Decision (June 2004), LM implemented a contingency action in 2009 by an Explanation of Significant Difference to include a pump-and-treat system using a single extraction well and treatment by zero

  16. [Groundwater].

    Science.gov (United States)

    González De Posada, Francisco

    2012-01-01

    From the perspective of Hydrogeology, the concept and an introductory general typology of groundwater are established. From the perspective of Geotechnical Engineering works, the physical and mathematical equations of the hydraulics of permeable materials, which are implemented, by electric analogical simulation, to two unique cases of global importance, are considered: the bailing during the construction of the dry dock of the "new shipyard of the Bahia de Cádiz" and the waterproofing of the "Hatillo dam" in the Dominican Republic. From a physical fundamental perspective, the theories which are the subset of "analogical physical theories of Fourier type transport" are related, among which the one constituted by the laws of Adolf Fick in physiology occupies a historic role of some relevance. And finally, as a philosophical abstraction of so much useful mathematical process, the one which is called "the Galilean principle of the mathematical design of the Nature" is dealt with.

  17. GLASS COMPOSITIONS FOR THE NEPHELINE PHASE III STUDY

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K.; Edwards, T.

    2009-06-29

    A series of 29 test glass compositions were selected for Phase III of the nepheline study using a combination of two approaches. The first approach was based on evaluating the glass composition region allowable by all of the Defense Waste Processing Facility (DWPF) Product Composition Control System (PCCS) models with the exception of the current nepheline discriminator. This approach was taken to determine whether there are glass compositions that, while predicted to crystallize nepheline upon slow cooling, would otherwise be acceptable for processing in the DWPF. The second approach was based on quasicrystalline theory of glass structure, which helped predict compositional regions where nepheline should form. A detailed description of this methodology is forthcoming. The selection strategy outlined here will provide an opportunity to determine experimentally whether the glasses that fail the current nepheline discriminator but pass the newly proposed nepheline discriminator are indeed free of nepheline after slow cooling. If this is the case, these data will serve as a significant step toward reducing conservatism in the current nepheline discriminator. The 29 glass compositions selected for testing address both the PCCS model and quasicrystalline theory approaches in evaluating both a reduction in conservatism for the current nepheline discriminator and possible implementation of the newly proposed discriminator based on glass structural theory. These glasses will be fabricated and characterized in the laboratory, with the results and conclusions described in a technical report.

  18. Thermodynamic considerations of the vapor phase reactions in III-nitride metal organic vapor phase epitaxy

    Science.gov (United States)

    Sekiguchi, Kazuki; Shirakawa, Hiroki; Chokawa, Kenta; Araidai, Masaaki; Kangawa, Yoshihiro; Kakimoto, Koichi; Shiraishi, Kenji

    2017-04-01

    We analyzed the metal organic vapor phase epitaxial growth mechanism of the III-nitride semiconductors GaN, AlN, and InN by first-principles calculations and thermodynamic analyses. In these analyses, we investigated the decomposition processes of the group III source gases X(CH3)3 (X = Ga, Al, In) at finite temperatures and determined whether the (CH3)2GaNH2 adduct can be formed or not. The results of our calculations show that the (CH3)2GaNH2 adduct cannot be formed in the gas phase in GaN metal organic vapor phase epitaxy (MOVPE), whereas, in AlN MOVPE, the formation of the (CH3)2AlNH2 adduct in the gas phase is exclusive. In the case of GaN MOVPE, trimethylgallium (TMG, [Ga(CH3)3]) decomposition into Ga gas on the growth surface with the assistance of H2 carrier gas, instead of the formation of the (CH3)2GaNH2 adduct, occurs almost exclusively. Moreover, in the case of InN MOVPE, the formation of the (CH3)2InNH2 adduct does not occur and it is relatively easy to produce In gas even without H2 in the carrier gas.

  19. 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

  20. 76 FR 33398 - 60-Day Notice of Proposed Information Collection; Passport Demand Forecasting Study Phase III...

    Science.gov (United States)

    2011-06-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE 60-Day Notice of Proposed Information Collection; Passport Demand Forecasting Study Phase III, 1405-0177 ACTION... Collection: Passport Demand Forecasting Study Phase III. OMB Control Number: OMB No. 1405-0177. Type of...

  1. Microbial Mineral Transformations at the Fe(II)/Fe(III) Redox Boundary for Solid Phase Capture of Strontium and Other Metal/Radionuclide Contaminants

    Energy Technology Data Exchange (ETDEWEB)

    F. G. Ferris; E. E. Roden

    2000-01-31

    The migration of {sup 90}Sr in groundwater is a significant environmental concern at former nuclear weapons production sites in the US and abroad. Although retardation of {sup 90}Sr transport relative to mean groundwater velocity is known to occur in contaminated aquifers, Sr{sup 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 {sup 90}Sr migration from sources of contamination. Chemical or biological processes capable of retarding or immobilizing Sr{sup 2+} in groundwater environments are of interest from the standpoint of understanding controls on subsurface Sr{sup 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{sup 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 {sup 90}Sr migrations in anaerobic subsurface environments. The demonstration of Sr{sup 2+} capture in carbonate mineral phases formed during bacterial HFO reduction and urea hydrolysis suggests that microbial carbonate mineral formation could contribute to Sr{sup 2+} retardation in groundwater environments. This process may also provide a mechanism for subsurface remediation of Sr{sup 2+} and other divalent metal contaminants that form insoluble carbonate precipitates.

  2. 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.

  3. 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.

  4. Underground Test Area Subproject Phase I Data Analysis Task. Volume VI - Groundwater Flow Model Documentation Package

    Energy Technology Data Exchange (ETDEWEB)

    None

    1996-11-01

    Volume VI of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the groundwater flow model data. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  5. Modeling contaminant transport in a three-phase groundwater system with the Freundlich-type retardation factor.

    Science.gov (United States)

    Kim, M; Kim, S B

    2007-02-01

    Colloid-facilitated contaminant transport was simulated in this study for the three-phase groundwater system where one or more sorption processes can be described with nonlinear sorption isotherm (Freundlich isotherm). A concise form of contaminant transport equation was derived from the mass balance equation of the contaminant. The developed model was numerically solved by the finite difference method along with the Picard iteration. The simulation results were used to quantitatively analyze the previously reported column data showing nonlinear sorption behavior. The analysis led to the following observations: (i) increases of the distribution coefficient of contaminant between the aqueous and solid phases (K(S)c) and the one between the dissolved natural organic matters and solid phase ( K(S)OM) generate less facilitation (i.e., late arrival of contaminant breakthrough curves (BTCs), and the distribution coefficient of contaminant between the aqueous and the solid phases (K(OM)c) gives the opposite result; (ii) the increase of the Freundlich constant for the sorption isotherm between the aqueous and the solid phases (N(S)c) yields the late arrival of BTC, and the other two Freundlich constants produce the opposite results; (iii) the Freundlich constants generally yield a sharper front as the BTC arrives at later pore volumes, while the distribution coefficients generally yield a more spread of the BTC as it arrives at later volumes. This modeling study shows that transport modeling provides a more efficient analyzing tool than the retardation factor alone concerning the colloid-facilitated contaminant transport with nonlinear sorption processes.

  6. Development og groundwater flow modeling techniques for the low-level radwaste disposal (III)

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Dae-Seok; Kim, Chun-Soo; Kim, Kyung-Soo; Park, Byung-Yoon; Koh, Yong-Kweon; Park, Hyun-Soo [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2000-12-01

    The project amis to establish the methodology of hydrogeologic assessment by the field application of the evaluation techniques gained and accumulated from the previous hydrogeological research works in Korea. The results of the project and their possible areas for application are (1) acquisition of detailed hydrogeologic information by using a borehole televiewer and a multipacker system, (2) establishing an integrated hydrogeological assessment method for fractured rocks, (3) acquisition of the fracture parameters for fracture modeling, (4) an inversion analysis of hydraulic parameters from fracture network modeling, (5) geostatistical methods for the spatial assignment of hydraulic parameters for fractured rocks, and (6) establishing the groundwater flow modeling procedure for a repository. 75 refs., 72 figs., 34 tabs. (Author)

  7. The role of groundwater governance in emergencies during different phases of natural disasters

    Science.gov (United States)

    Vrba, Jaroslav

    2016-03-01

    The establishment of water governance in emergency situations supports timely and effective reaction with regard to the risk and impact of natural disasters on drinking-water supplies and populations. Under such governance, emergency activities of governmental authorities, rescue and aid teams, water stakeholders, local communities and individuals are coordinated with the objective to prevent and/or mitigate disaster impact on water supplies, to reduce human suffering due to drinking-water failure during and in the post-disaster period, and to manage drinking-water services in emergency situations in an equitable manner. The availability of low-vulnerability groundwater resources that have been proven safe and protected by geological features, and with long residence time, can make water-related relief and rehabilitation activities during and after an emergency more rapid and effective. Such groundwater resources have to be included in water governance and their exploration must be coordinated with overall management of drinking-water services in emergencies. This paper discusses institutional and technical capacities needed for building effective groundwater governance policy and drinking-water risk and demand management in emergencies. Disaster-risk mitigation plans are described, along with relief measures and post-disaster rehabilitation and reconstruction activities, which support gradual renewal of drinking-water services on the level prior to the disaster. The role of groundwater governance in emergencies differs in individual phases of disaster (preparedness, warning, impact/relief, rehabilitation). Suggested activities and actions associated with these phases are summarized and analysed, and a mode of their implementation is proposed.

  8. Novel Elastomeric Closed Cell Foam - Nonwoven Fabric Composite Material (Phase III)

    Science.gov (United States)

    2008-10-01

    AFRL-RX-TY-TR-2009-4577 NOVEL ELASTOMERIC CLOSED CELL FOAM – NONWOVEN FABRIC COMPOSITE MATERIAL (PHASE III) Davis, Stephen C...07-OCT-2009 Novel Elastomeric Closed Cell Foam - Nonwoven Fabric Composite Material (Phase III) FA4819-07-D-0001 62102F 4347 D2 4347D23A Davis...develop novel closed cell foam- nonwoven fabric composites to commercial scale evaluation. Armacell tasks focused on foam optimization for commercial

  9. Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review.

    Directory of Open Access Journals (Sweden)

    Miranta Antoniou

    Full Text Available Personalized medicine is a growing area of research which aims to tailor the treatment given to a patient according to one or more personal characteristics. These characteristics can be demographic such as age or gender, or biological such as a genetic or other biomarker. Prior to utilizing a patient's biomarker information in clinical practice, robust testing in terms of analytical validity, clinical validity and clinical utility is necessary. A number of clinical trial designs have been proposed for testing a biomarker's clinical utility, including Phase II and Phase III clinical trials which aim to test the effectiveness of a biomarker-guided approach to treatment; these designs can be broadly classified into adaptive and non-adaptive. While adaptive designs allow planned modifications based on accumulating information during a trial, non-adaptive designs are typically simpler but less flexible.We have undertaken a comprehensive review of biomarker-guided adaptive trial designs proposed in the past decade. We have identified eight distinct biomarker-guided adaptive designs and nine variations from 107 studies. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. We have graphically displayed the current biomarker-guided adaptive trial designs and summarised the characteristics of each design.Our in-depth overview provides future researchers with clarity in definition, methodology and terminology for biomarker-guided adaptive trial designs.

  10. Phase I/II adaptive design for drug combination oncology trials

    OpenAIRE

    Wages, Nolan A.; Conaway, Mark R.

    2014-01-01

    Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity ...

  11. Evaluation of DCS III Transmission Alternatives. Phase 1A Report.

    Science.gov (United States)

    1980-05-26

    Waves . . . . ... . 3-13 3.4 EHF Satellite Communicatins ... 3-15 *3.5 Optical Fibers . . . . . . . . . . . . . . . . . . . . . . 3-17 3.5.1 Optical Fiber...Defense and Space Systems Group, TRW Inc. and by TRW’s subcontractor, Page Communications Engineers, Inc., Northrop Corporation . 1.1 Purpose of the DCS III...tactical and long haul communicatins systems study have been sponsored by the U.S. Army, and the U.S. Navy also is working on submarine fiber optics

  12. Groundwater flow modelling under ice sheet conditions in Greenland (phase II)

    Energy Technology Data Exchange (ETDEWEB)

    Jaquet, Olivier; Namar, Rabah; Siegel, Pascal [In2Earth Modelling Ltd, Lausanne (Switzerland); Jansson, Peter [Dept. of Physical Geography and Quaternary Geology, Stockholm Univ., Stockholm (Sweden)

    2012-11-15

    Within the framework of the GAP project, this second phase of geosphere modelling has enabled the development of an improved regional model that has led to a better representation of groundwater flow conditions likely to occur under ice sheet conditions. New data in relation to talik geometry and elevation, as well as to deformation zones were integrated in the geosphere model. In addition, more realistic hydraulic properties were considered for geosphere modelling; they were taken from the Laxemar site in Sweden. The geological medium with conductive deformation zones was modelled as a 3D continuum with stochastically hydraulic properties. Surface and basal glacial meltwater rates provided by a dynamic ice sheet model were assimilated into the groundwater flow model using mixed boundary conditions. The groundwater flow system is considered to be governed by infiltration of glacial meltwater in heterogeneous faulted crystalline rocks in the presence of permafrost and taliks. The characterisation of the permafrost-depth distribution was achieved using a coupled description of flow and heat transfer under steady state conditions. Using glaciological concepts and satellite data, an improved stochastic model was developed for the description at regional scale for the subglacial permafrost distribution in correlation with ice velocity and bed elevation data. Finally, the production of glacial meltwater by the ice sheet was traced for the determination of its depth and lateral extent. The major improvements are related to the type and handling of the subglacial boundary conditions. The use of meltwater rates provided by an ice sheet model applied as input to a mixed boundary condition enables to produce a more plausible flow field in the Eastern part of the domain, in comparison to previous modelling results (Jaquet et al. 2010). In addition, the integration of all potential taliks within the modelled domain provides a better characterisation of the likely groundwater

  13. 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.

  14. Phases I–III Clinical Trials Using Adult Stem Cells

    OpenAIRE

    Ricardo Sanz-Ruiz; Enrique Gutiérrez Ibañes; Adolfo Villa Arranz; María Eugenia Fernández Santos; Pedro L. Sánchez Fernández; Francisco Fernández-Avilés

    2010-01-01

    First randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease. Nevertheless, some trials have shown that conflicting results and uncertainties remain in the case of mechanisms of action and possible ways to improve clinical impact of stem cells in cardiac repair. In this paper we will examine the evidence available, analyze the main phase I and II randomize...

  15. High-resolution analysis of the duodenal interdigestive phase III in humans.

    Science.gov (United States)

    Castedal, M; Abrahamsson, H

    2001-10-01

    To study the spatial organization of the propagating pressure waves of duodenal phase III, we performed fasting antroduodenal high-resolution manometry with a 16-channel catheter in 12 healthy subjects. The phase III pressure waves diverged in an anterograde and retrograde direction from the start site of each pressure wave. The pressure waves maintained this configuration as the activity front moved distally in the duodenum. The start site of the pressure waves moved gradually to a point approximately 12 cm (median) distal to the pylorus and remained at this point for about 40% of the phase III time before moving further distally. The length of retrograde pressure wave propagation increased to 6 cm (median) as the pressure wave origin moved aborally to a point 10-14 cm distal to the pylorus, and then decreased when the origin of pressure waves reached the distal end of the duodenum. Bidirectional pressure waves dominated in both retrograde and anterograde activity fronts. Three pressure-wave mechanisms behind the duodenal phase IV were observed. Isolated pyloric pressure waves were absent during late duodenal phase III retroperistalsis. Thus, a number of new features of the duodenal phase III-related motility were observed using high-temporospatial resolution recordings.

  16. Phases I–III Clinical Trials Using Adult Stem Cells

    Directory of Open Access Journals (Sweden)

    Ricardo Sanz-Ruiz

    2010-01-01

    Full Text Available First randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease. Nevertheless, some trials have shown that conflicting results and uncertainties remain in the case of mechanisms of action and possible ways to improve clinical impact of stem cells in cardiac repair. In this paper we will examine the evidence available, analyze the main phase I and II randomized clinical trials and their limitations, discuss the key points in the design of future trials, and depict new directions of research in this fascinating field.

  17. Local Area Network Implementation: Moving toward Phase III.

    Science.gov (United States)

    Hoehl, Susan B.

    1989-01-01

    Describes a LAN (local area network)-based automation project which has neared completion of the first phase of implementation at the Health Sciences Library of Allegheny General Hospital (Pittsburgh, PA). Changes in the library and its objectives with increased technological experience are examined. Diagrams of the current LAN configuration and…

  18. 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.

  19. Phase transitions in tumor growth: III vascular and metastasis behavior

    Science.gov (United States)

    Llanos-Pérez, J. A.; Betancourt-Mar, J. A.; Cocho, G.; Mansilla, R.; Nieto-Villar, José Manuel

    2016-11-01

    We propose a mechanism for avascular, vascular and metastasis tumor growth based on a chemical network model. Vascular growth and metastasis, appear as a hard phase transition type, as "first order", through a supercritical Andronov-Hopf bifurcation, emergence of limit cycle and then through a cascade of bifurcations type saddle-foci Shilnikov's bifurcation. Finally, the thermodynamics framework developed shows that the entropy production rate, as a Lyapunov function, indicates the directional character and stability of the dynamical behavior of tumor growth according to this model.

  20. Phase III (and maybe IV of the SIMPLE dark matter search experiment at the LSBB

    Directory of Open Access Journals (Sweden)

    Girard T.A.

    2014-01-01

    Full Text Available with the recent conclusion of Phase II, SIMPLE has ended its use of Superheated Droplet Detectors (SDD in the WIMP search effort. An in-progress Phase III comprises a transition to larger mass bubble chamber technology, using many of the lessons gained from the previous phase since the underlying physics is identical. We describe the progress of the activities, to include several ∼1 kg prototype chambers, each 4× the total Phase II active mass, which are undergoing testing, prior to a rescaling to a 50 kg capacity within a Phase IV modular 1 ton detector for a definitive astroparticle search effort.

  1. Fe(III INVOLVEMENT IN THE PHOTODEGRADATION OF ASPIRIN IN HOMOGENEOUS AND HETEROGENEOUS PHASE

    Directory of Open Access Journals (Sweden)

    Y MAMERI

    2014-07-01

    Full Text Available The photocatalytic degradation of Aspirin (ASP induced by Fe(III in homogeneous (ASP-Fe(III-citrate complex and heterogeneous phase (ASP-Goethite was studied in aqueous solution up on irradiation at 365nm and by solar light.  A dark investigation of system containing a mixture of aspirin and Fe (III reveals no interaction in homogeneous phase but in heterogeneous phase, the interaction observed was traduced by aspirin adsorption on Goethite in aqueous solution. Under irradiation, Fe(III-Citrate complex enhance the photooxidation of ASP; a pseudo-first order kinetic model was employed to discuss the results. Against in heterogeneous phase, kinetics is slower and the process is accelerated at acidic pH. The involvement of HO● radicals has been established because of the influence of tertiobutanol used as a scavenger. The photodegradation of ASP in the mixture ASP-Fe(III-Cit and ASP-Goethite under solar light was significantly accelerated in comparison with artificial irradiation at 365nm.

  2. Benzocaine polymorphism: pressure-temperature phase diagram involving forms II and III.

    Science.gov (United States)

    Gana, Inès; Barrio, Maria; Do, Bernard; Tamarit, Josep-Lluís; Céolin, René; Rietveld, Ivo B

    2013-11-18

    Understanding the phase behavior of an active pharmaceutical ingredient in a drug formulation is required to avoid the occurrence of sudden phase changes resulting in decrease of bioavailability in a marketed product. Benzocaine is known to possess three crystalline polymorphs, but their stability hierarchy has so far not been determined. A topological method and direct calorimetric measurements under pressure have been used to construct the topological pressure-temperature diagram of the phase relationships between the solid phases II and III, the liquid, and the vapor phase. In the process, the transition temperature between solid phases III and II and its enthalpy change have been determined. Solid phase II, which has the highest melting point, is the more stable phase under ambient conditions in this phase diagram. Surprisingly, solid phase I has not been observed during the study, even though the scarce literature data on its thermal behavior appear to indicate that it might be the most stable one of the three solid phases.

  3. 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.

  4. Age Strengthening of Gray Cast Iron Phase III

    Energy Technology Data Exchange (ETDEWEB)

    Von L. Richards; Wayne Nicola

    2003-06-26

    The primary objective of this research is to identify the age strengthening mechanism in gray and ductile cast iron, and to quantify the parameters that control it. It is also to contribute to a new predictive model for gray and ductile iron strength and hardness. This work shows that age strengthening occurs on a sigmoidal-logarithmic scale in gray and ductile cast irons, to a statistically significant extent. This is similar to Avrami-Johnson-Mehl kinetics for phase transformations in metals. It occurs in both cupola-melted iron and induction melted iron. However, it does not happen in all compositions. We have developed some understanding of the process. Data suggests that nitrogen and nitride-forming trace elements have a significant role in the process, but that is yet not fully characterized. Also, the time dependence of the bulk hardness and strength increase, the nano-scale precipitation evidence from neutron scattering, differential scanning calorimetry results and matrix micro-hardness increase in ferrite all indicate that age strengthening occurs by a precipitation or pre-precipitate cluster formation mechanism.

  5. What have we learnt from ISAAC phase III in the Asia-Pacific rim?.

    Science.gov (United States)

    Fok, Annie O L; Wong, Gary W K

    2009-04-01

    International Study of Asthma and Allergies in Childhood (ISAAC) phase III had provided a worldwide map of epidemiology of asthma and allergic diseases, as well as the changes in prevalence rate of these diseases when compared to data obtained in phase I. The wide variations of environmental factors and ethnic background in Asia provide excellent opportunities for research into the environmental and genetic determinants of asthma and allergies. This review summarizes important lessons learnt from ISAAC phase III results from Asia on asthma and allergy. ISAAC phase III provided epidemiological evidence of the wide variation and increasing prevalence of asthma and allergy in many Asian countries. When compared to other regions of the world, Asia has a relatively lower prevalence of asthma and allergic diseases. Comparative studies of populations of the same ethnic group living in different environments reveal striking disparity in prevalence of asthma and allergic diseases. The established risk factors could not explain the secular trend and variations of asthma prevalence in different Asian countries. Further research is needed in this rapidly changing region of Asia in order to identify the protective or risk factors associated with the development of asthma. ISAAC phase III provides standardized data on the prevalence and burden of asthma and allergy in the Asia-Pacific region. Further research is needed to reveal the underlying factors responsible for the wide variations in disease manifestations in the region.

  6. 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.

  7. 76 FR 53704 - 30-Day Notice of Proposed Information Collection: Passport Demand Forecasting Study Phase III...

    Science.gov (United States)

    2011-08-29

    ... the Office of Management and Budget (OMB) for approval in accordance with the Paperwork Reduction Act of 1995. Title of Information Collection: Passport Demand Forecasting Study Phase III. OMB Control.... Frequency: Monthly. Obligation to Respond: Voluntary. DATES: Submit comments to the Office of Management...

  8. 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.

  9. Factors associated with reduced early survival in the Oxford phase III medial unicompartment knee replacement

    NARCIS (Netherlands)

    Kuipers, Bart M.; Kollen, Boudewijn J.; Bots, Peter C. Kaijser; Burger, Bart J.; van Raay, Jos J. A. M.; Tulp, Niek J. A.; Verheyen, Cees C. P. M.

    2010-01-01

    The aim of this study was to determine the prognostic value of preoperative patellofemoral osteoarthritis, BMI and age for implant Survival of unicompartmental knee arthroplasty (UKA) performed in patients meeting strict admission criteria. The data and radiographs of 437 unilateral Oxford phase III

  10. 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.

  11. Inference of unexpected genetic relatedness among individuals in HapMap Phase III.

    Science.gov (United States)

    Pemberton, Trevor J; Wang, Chaolong; Li, Jun Z; Rosenberg, Noah A

    2010-10-08

    The International Haplotype Map Project (HapMap) has provided an essential database for studies of human population genetics and genome-wide association. Phases I and II of the HapMap project generated genotype data across ∼3 million SNP loci in 270 individuals representing four populations. Phase III provides dense genotype data on ∼1.5 million SNPs, generated by Illumina and Affymetrix platforms in a larger set of individuals. Release 3 of phase III of the HapMap contains 1397 individuals from 11 populations, including 250 of the original 270 phase I and phase II individuals and 1147 additional individuals. Although some known relationships among the phase III individuals have been described in the data release, the genotype data that are currently available provide an opportunity to empirically ascertain previously unknown relationships. We performed a systematic analysis of genetic relatedness and were able not only to confirm the reported relationships, but also to detect numerous additional, previously unidentified pairs of close relatives in the HapMap sample. The inferred relative pairs make it possible to propose standardized subsets of unrelated individuals for use in future studies in which relatedness needs to be clearly defined.

  12. Concurrence of aqueous and gas phase contamination of groundwater in the Wattenberg oil and gas field of northern Colorado.

    Science.gov (United States)

    Li, Huishu; Son, Ji-Hee; Carlson, Kenneth H

    2016-01-01

    The potential impact of rapid development of unconventional oil and natural gas resources using hydraulic fracturing and horizontal drilling on regional groundwater quality has received significant attention. Major concerns are methane or oil/gas related hydrocarbon (such as TPHs, BTEX including benzene, toluene, ethybenzene and xylene) leaks into the aquifer due to the failure of casing and/or stray gas migration. Previously, we investigated the relationship between oil and gas activity and dissolved methane concentration in a drinking water aquifer with the major finding being the presence of thermogenic methane contamination, but did not find detectable concentrations of TPHs or BTEX. To understand if aqueous and gas phases from the producing formation were transported concurrently to drinking water aquifers without the presence of oil/gas related hydrocarbons, the ionic composition of three water groups was studied: (1) uncontaminated deep confined aquifer, (2) suspected contaminated groundwater - deep confined aquifer containing thermogenic methane, and (3) produced water from nearby oil and gas wells that would represent aqueous phase contaminants. On the basis of quantitative and spatial analysis, we identified that the "thermogenic methane contaminated" groundwater did not have similarities to produced water in terms of ionic character (e.g. Cl/TDS ratio), but rather to the "uncontaminated" groundwater. The analysis indicates that aquifer wells with demonstrated gas phase contamination have not been contacted by an aqueous phase from oil and gas operations according to the methodology we use in this study and the current groundwater quality data from COGCC. However, the research does not prove conclusively that this the case. The results may provide insight on contamination mechanisms since improperly sealed well casing may result in stray gas but not aqueous phase transport.

  13. Two-phase treatment of patients with crossbite and tendency toward skeletal Class III malocclusion

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Machado Bayerl

    2014-08-01

    Full Text Available Angle Class III malocclusion is characterized by an inadequate anteroposterior dental relationship which may or may not be accompanied by skeletal changes. In general, patients are distressed by a significantly compromised facial aspect which, when associated with a deficient middle third, encourages patients to seek treatment. This article reports a two-phase treatment carried out in a female patient aged six years and six months with a tendency towards a Class III skeletal pattern. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO. It is representative of the Discrepancy Index (DI category, and fulfills part of the requirements for obtaining BBO Diploma.

  14. 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.

  15. Evaluation of hydrothermal resources of North Dakota. Phase III final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Harris, K.L.; Howell, F.L.; Wartman, B.L.; Anderson, S.B.

    1982-08-01

    The hydrothermal resources of North Dakota were evaluated. This evaluation was based on existing data on file with the North Dakota Geological Survey (NDGS) and other state and federal agencies, and field and laboratory studies conducted. The principal sources of data used during the study were WELLFILE, the computer library of oil and gas well data developed during the Phase I study, and WATERCAT, a computer library system of water well data assembled during the Phase II study. A field survey of the shallow geothermal gradients present in selected groundwater observation holes was conducted. Laboratory determinations of the thermal conductivity of core samples were done to facilitate heat-flow calculations on those holes-of-convenience cased.

  16. In situ chemical oxidation of contaminated groundwater by persulfate: decomposition by Fe(III)- and Mn(IV)-containing oxides and aquifer materials.

    Science.gov (United States)

    Liu, Haizhou; Bruton, Thomas A; Doyle, Fiona M; Sedlak, David L

    2014-09-02

    Persulfate (S2O8(2-)) is being used increasingly for in situ chemical oxidation (ISCO) of organic contaminants in groundwater, despite an incomplete understanding of the mechanism through which it is converted into reactive species. In particular, the decomposition of persulfate by naturally occurring mineral surfaces has not been studied in detail. To gain insight into the reaction rates and mechanism of persulfate decomposition in the subsurface, and to identify possible approaches for improving its efficacy, the decomposition of persulfate was investigated in the presence of pure metal oxides, clays, and representative aquifer solids collected from field sites in the presence and absence of benzene. Under conditions typical of groundwater, Fe(III)- and Mn(IV)-oxides catalytically converted persulfate into sulfate radical (SO4(•-)) and hydroxyl radical (HO(•)) over time scales of several weeks at rates that were 2-20 times faster than those observed in metal-free systems. Amorphous ferrihydrite was the most reactive iron mineral with respect to persulfate decomposition, with reaction rates proportional to solid mass and surface area. As a result of radical chain reactions, the rate of persulfate decomposition increased by as much as 100 times when benzene concentrations exceeded 0.1 mM. Due to its relatively slow rate of decomposition in the subsurface, it can be advantageous to inject persulfate into groundwater, allowing it to migrate to zones of low hydraulic conductivity where clays, metal oxides, and contaminants will accelerate its conversion into reactive oxidants.

  17. 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

    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...... worse baseline prognostic features. However, patients treated with immunotherapy had similar survival outcomes regardless of eligibility. Conclusion Over half of the patients evaluated for systemic treatment of MM are not represented in phase III registration immunotherapy trials. The data reveal 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....

  18. Alirocumab for hyperlipidemia: ODYSSEY Phase III clinical trial results and US FDA approval indications.

    Science.gov (United States)

    Roth, Eli M

    2016-03-01

    A new class of lipid-lowering drugs, inhibitors of PCSK9 has been generating impressive clinical trial data over the last several years, and alirocumab (Praluent) has become the first to be approved by the US FDA. Alirocumab has been shown to lower low density lipoprotein cholesterol by 45-62% with a safety profile generally comparable to placebo. Alirocumab is a monoclonal antibody to PCSK9 administered subcutaneously and has been evaluated in 16 Phase III clinical trials, the majority of which have been enrolled or completed. This article will be a review of the available Phase III safety and efficacy data of the ODYSSEY studies including a brief description of each of the 16 studies.

  19. Phase I-II study of isotopic immunoglobulin therapy for primary liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ettinger, D.S.; Order, S.E.; Wharam, M.D.; Parker, M.K.; Klein, J.L.; Leichner, P.K.

    1982-02-01

    A phase I-II study of isotopic immunoglobulin therapy was performed in 18 patients with primary liver cancer; 14 were evaluable for toxicity. The patients received a dose of 37-157 millicuries of 131I-labeled antibody. The dose-limiting factor appears to be hematologic toxicity, especially thrombocytopenia. An objective antitumor effect was seen in six of nine patients who were evaluable for response. Present results suggest that further clinical studies with isotopic immunoglobulin are indicated.

  20. Spin Manipulation through geometric phase in III-V semiconductor quantum dots

    Science.gov (United States)

    Prbahakar, Sanjay; Melnik, Roderick

    2015-03-01

    A more robust technique is proposed to flip the spin completely through geometric phase in III-V semiconductor quantum dots (QDs). We transport the QDs adiabatically in a closed loop along the circular trajectory in the plane of two dimensional electron gas with the application of time dependent gate controlled electric fields and investigate the manipulation of Berry phase with the spin-orbit couplings. Here we show that both the Rashba and the Dresselhaus couplings are present for inducing a phase necessary for spin flip. If one of them is absent, the induced phase is trivial and irrelevant for spin-flip (Phys. Rev. B 89, 245310 (2014), Applied Physics Letters 104, 142411 (2014)). We acknowledge the funding agency: Natural Sciences and Engineering Research Council of Canada and Canada Research Chair Program.

  1. 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

  2. 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.

  3. [Phase III clinical trial using autologous mesenchymal stem cells for stroke patients].

    Science.gov (United States)

    Honmou, Osamu

    2016-04-01

    We conduct a double-blind randomized placebo-controlled clinical trial (Phase III: confirmatory trial) of intravenous infusion of autologous mesenchymal stem cells for cerebral infarction patients. The objectives of this study were to examine feasibility, safety, and efficacy of cell therapy using auto serum-expanded autologous mesenchymal stem cells derived from bone marrow in the stroke patients. Inclusion criteria is (1) Cerebral infarction onset within 40 days, (2) Supra-tentorial cerebral infarction(NINDS-III 1990) diagnosed by MRI(or CT), MRA (3D-CTA or DSA), ECG, chest X-ray etc., (3) Classified under grade 4 or 5 of mRS (modified Rankin scale), (4) Age between 20 to 80, (5) The written informed consent from subjects and legal representative is provided.

  4. Two-phase treatment of patients with crossbite and tendency toward skeletal Class III malocclusion.

    Science.gov (United States)

    Bayerl, Maria de Lourdes Machado

    2014-01-01

    Angle Class III malocclusion is characterized by an inadequate anteroposterior dental relationship which may or may not be accompanied by skeletal changes. In general, patients are distressed by a significantly compromised facial aspect which, when associated with a deficient middle third, encourages patients to seek treatment. This article reports a two-phase treatment carried out in a female patient aged six years and six months with a tendency towards a Class III skeletal pattern. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO). It is representative of the category with Discrepancy Index (DI) equal or greater than 10, and fulfills part of the requirements for obtaining BBO Diploma.

  5. Modeling mineral phase change chemistry of groundwater in a rural-urban fringe.

    Science.gov (United States)

    Singh, S K; Srivastava, Prashant K; Gupta, M; Mukherjee, S

    2012-01-01

    This research paper aims to determine the genetic origin of the chemical elements in groundwater. It deals with the results of physicochemical parameters, to evaluate the hydro-geochemistry of groundwater in rural-urban fringe of district Bareilly, India. Pre- and post-monsoon sampling has been carried out, which reveals inter-seasonal variability effect on the hydro-geochemical processes. Geochemical modeling especially computation of saturation index was undertaken using the WATEQ4F model. Majority of samples fall in the category of undersaturation, which further suggests that groundwater still has potential to dissolve more minerals. Chemical categorizations of groundwater samples were performed with the help of the Aquachem model. Grouping of groundwater on the Piper diagram reveals a common composition and origin. In most of the area, water facies is of Ca(2+)-HCO(3)(-) type in both the seasons. It also indicates that in pre-monsoon, ion exchange is the dominant process, whereas in post-monsoon, both ion exchanges as well as reverse ion exchanges are reported in the groundwater of the study area.

  6. [Alemtuzumab for relapsing-remitting multiple sclerosis. Results of two randomized controlled phase III studies].

    Science.gov (United States)

    Klotz, L; Meuth, S G; Kieseier, B; Wiendl, H

    2013-08-01

    In November 2012 the results of 2 clinical phase III trials were published which addressed the effects of alemtuzumab in patients with relapsing-remitting multiple sclerosis (MS). In the CARE-MS-I study patients with early untreated MS (EDSS ≤ 3.0, disease duration alemtuzumab in patients with persisting disease activity under standard disease-modifying treatment (EDSS ≤ 5.0, disease duration alemtuzumab compared to interferon in terms of reduction of relapse rate as well as the number of new or enlarging T2 lesions and gadolinium-enhancing lesions. Moreover, the CARE-MS-II study showed a significant delay in disease progression by alemtuzumab. The portfolio and the frequency of relevant side effects, such as infusion-related reactions, development of secondary autoimmunity or infections were within the expected range. Taken together these studies confirm the high anti-inflammatory efficacy of alemtuzumab and hence provide the first evidence of superiority of a monotherapy in direct comparison to standard disease-modifying treatment in two phase III trials in relapsing-remitting MS. These data in the context of the mode of action of alemtuzumab provide evidence for the relevance of immune cells, especially T cells, in the pathophysiology of MS. Experience with long-term effects of alemtuzumab, e.g. from the phase II extension trial as well as the side effect profile argue in favor of a sustained reprogramming of the immune system as a consequence of immune cell depletion by alemtuzumab.

  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. 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.

  9. 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.

  10. 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

  11. ENGINEERING DEVELOPMENT OF COAL-FIRED HIGH PERFORMANCE POWER SYSTEMS PHASE II AND III

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-30

    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: à thermal efficiency (HHV) >47%; à NOx, SOx, and particulates <10% NSPS (New Source Performance Standard); à coal providing >65% of heat input; à all solid wastes benign; à 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&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: à Task 2.2 HITAF Air Heaters; à Task 6 HIPPS Commercial Plant Design Update.

  12. Application of Bayesian hierarchical models for phase I/II clinical trials in oncology.

    Science.gov (United States)

    Yada, Shinjo; Hamada, Chikuma

    2017-03-01

    Treatment during cancer clinical trials sometimes involves the combination of multiple drugs. In addition, in recent years there has been a trend toward phase I/II trials in which a phase I and a phase II trial are combined into a single trial to accelerate drug development. Methods for the seamless combination of phases I and II parts are currently under investigation. In the phase II part, adaptive randomization on the basis of patient efficacy outcomes allocates more patients to the dose combinations considered to have higher efficacy. Patient toxicity outcomes are used for determining admissibility to each dose combination and are not used for selection of the dose combination itself. In cases where the objective is not to find the optimum dose combination solely for efficacy but regarding both toxicity and efficacy, the need exists to allocate patients to dose combinations with consideration of the balance of existing trade-offs between toxicity and efficacy. We propose a Bayesian hierarchical model and an adaptive randomization with consideration for the relationship with toxicity and efficacy. Using the toxicity and efficacy outcomes of patients, the Bayesian hierarchical model is used to estimate the toxicity probability and efficacy probability in each of the dose combinations. Here, we use Bayesian moving-reference adaptive randomization on the basis of desirability computed from the obtained estimator. Computer simulations suggest that the proposed method will likely recommend a higher percentage of target dose combinations than a previously proposed method.

  13. Phase III Advanced Anodes and Cathodes Utilized in Energy Efficient Aluminum Production Cells

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-11-05

    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

  14. Groundwater Waves in a Coastal Fractured Aquifer of the Third Phase Qinshan Nuclear Power Engineering Field

    Institute of Scientific and Technical Information of China (English)

    ZHOU Nian-qing; TANG Yi-qun; TANG He-ping

    2005-01-01

    Tidal fluctuations of Hangzhou Bay produce progressive pressure waves in adjacent field fractured aquifers, as the pressure waves propagate, groundwater levels and hydraulic gradients continuously fluctuate. The effect of tidal fluctuations on groundwater flow can be determined using the mean hydraulic gradient that can be calculated by comparing mean ground and surface water elevations. Tidal fluctuation is shown to affect the piezometer readings taken in a nearshore fractured aquifer around the nuclear power engineering field. Continuous monitoring of a network of seven piezometers provided relations between the tidal cycle and the piezometer readings. The relations can be expressed in times of a time and amplitude scaling factor. The time lag and the tidal effi ciency factor and wavelength are calculated using these parameters. It provides significant scientific basis to prevent tide and groundwater for the nuclear power engineering construction and safety run of nuclear power station in the future.

  15. TNF phase III signalling in tolerant cells is tightly controlled by A20 and CYLD.

    Science.gov (United States)

    Bikker, Rolf; Christmann, Martin; Preuß, Katharina; Welz, Bastian; Friesenhagen, Judith; Dittrich-Breiholz, Oliver; Huber, René; Brand, Korbinian

    2017-09-01

    Following the acute phase of an inflammatory reaction, a strictly controlled resolution of inflammation is necessary. A dysregulation of this process leads to hyperinflammation, chronic inflammatory disease, or immune paralysis. Different mechanisms participate in the coordinated termination of the inflammatory process, e.g. the expression of antiinflammatory molecules and different forms of tolerance. To better understand the processes which mediate resolution of TNF-dependent inflammation and induce tolerance, it is necessary to characterize the signal transduction quality during TNF long-term (pre)incubation. Within a time frame from 12 to 48h, designated as phase III of the TNF response, we measured an ongoing, constitutive activation of TNFR1/NF-κB-dependent pathways in monocytic cells. Phase III signalling which was also named "constitutive signaling in TNF tolerant cells" induces the expression of low- and high-sensitive target genes including A20 which is differentially regulated by transcriptional and proteolytic events. A20 strictly controls TNF long-term constitutive signalling in an IκB kinase complex- and partially RIP-dependent manner supported by adjuvant ABIN1. In addition, CYLD proteins participate in the regulation of this late-phase signal transduction, whereas downstream molecules such as Bcl3 and p50 are not involved. A20 and CYLD are expressed with different mRNA kinetics resulting in a strong or only a modest increase in protein levels, respectively. The identification of mechanisms which contribute to the termination of inflammation will provide additional diagnostic and therapeutic aspects to specifically diagnose certain aspects of inflammation and specifically modulate them. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Structure of Fe(III) precipitates generated by Fe(0) electrocoagulation in the presence of groundwater ions

    Science.gov (United States)

    van Genuchten, C. M.; Pena, J.; Addy, S. E.; Gadgil, A. J.

    2012-12-01

    Electrocoagulation (EC) using Fe(0) electrodes is an inexpensive and efficient technology capable of removing a variety of contaminants from water supplies. Because of its ease of use and modest electricity and Fe(0) requirements, EC has potential as an arsenic-removal technology for rural South Asia, where millions drink groundwater contaminated by arsenic. In EC, a small external voltage applied to a sacrificial Fe(0) anode in contact with an electrolyte (e.g. pumped groundwater containing arsenic) promotes the oxidative dissolution of Fe ions, which polymerize and create reactive hydrous ferric oxides (HFO) in-situ with a high affinity for binding contaminants. The chemical composition of the electrolyte influences EC performance. For example, major inorganic ions present in groundwater (e.g. Ca, Mg, P, As(V), Si) alter the pathway by which FeO6 oligomers polymerize to form crystalline Fe (oxyhydr)oxide minerals. Because the precipitate structure largely determines properties that govern the efficiency of EC systems (e.g. precipitate reactivity and colloidal stability), it is essential to understand the individual and interdependent structural effects of common groundwater ions. In this work, we integrate Fe K-edge EXAFS spectroscopy with the Pair Distribution Function (PDF) technique to create a detailed description of EC precipitate structure as a function of electrolyte chemistry. EC precipitate samples were generated in a range of individual and combined concentrations of Ca, Mg, P, As(V), and Si, encompassing most of the typical levels found in natural groundwater. Combining complementary EXAFS and PDF techniques with batch uptake experiments and general chemical reasoning, we obtain structural representations of EC precipitates that are inaccessible with any single characterization technique. Our results indicate that the presence of As(V), P, and Si oxyanions promote the formation of nanoscale material bearing similar, but not identical, intermediate

  17. A modified varying-stage adaptive phase II/III clinical trial design.

    Science.gov (United States)

    Dong, Gaohong; Vandemeulebroecke, Marc

    2016-07-01

    Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jing, L.; Rutqvist, J.; Stephansson, O. [eds.] [Royal Inst. of Tech., Stockholm (Sweden); Tsang, C.F. [ed.] [California Univ., Berkeley, CA (United States). Lawrence Berkeley Lab.; Kautsky, F. [ed.] [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

    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.

  19. Phase II Hydrologic Data for the Groundwater Flow and Contaminant Transport Model of Corrective Action Unit 98: Frenchman Flat, Nye County, Nevada, Rev. No.: 0

    Energy Technology Data Exchange (ETDEWEB)

    John McCord

    2004-12-01

    This report documents pertinent hydrologic data and data analyses as part of the Phase II Corrective Action Investigation (CAI) for Frenchman Flat (FF) Corrective Action Unit (CAU): CAU 98. The purpose of this data compilation and related analyses is to provide the primary reference to support the development of the Phase II FF CAU groundwater flow model.

  20. 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.

    Science.gov (United States)

    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 %. FigureThe new ion imprinted polymer was prepared and used for the separation of ruthenium from water and most complex environmental samples, such as road dust and platinum ore (CRM SARM 76) prior ETAAS determination.

  1. Lunar exploration phase III: Launch window and trajectory design for a lunar lander

    Science.gov (United States)

    Li, Jingyang; Yang, Hongwei; Baoyin, Hexi

    2015-09-01

    The lunar exploration phase III mission is a part of the China Aerospace Science and Technology Corporation's lunar exploration program that will perform a soft-landing and sample return from the Moon to test the key technologies that are required for human lunar missions. This paper focuses primarily on the trajectory design and orbital launch window generation for a lunar probe that are consistent with the constraints imposed by third phase of lunar exploration. Two categories of trajectories are explored: Earth-to-Moon and Moon-to-Earth. With the patched conic technique, the analytical and modified analytical models of the transfer trajectories are developed. The requirement of high-latitude landing for the return phase trajectory is considered in the modified model. By varying the initial input conditions and with a fast convergence iteration scheme, different characteristics of the transfer trajectory are generated. The orbital launch windows are established to study the mission sensitivities to time and fuel consumption and to provide a launch timetable that is compatible with this mission's requirements. The lunar surface stay time is analyzed for different conditions. The high-fidelity gravitational model is introduced to demonstrate the accuracy and convergence behavior of the analytical solution. The design method can also be used as a basis for the future human lunar missions.

  2. 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

  3. Phase transitions in Group III-V and II-VI semiconductors at high pressure

    Science.gov (United States)

    Yu, S. C.; Liu, C. Y.; Spain, I. L.; Skelton, E. F.

    1979-01-01

    The structures and transition pressures of Group III-V and II-VI semiconductors and of a pseudobinary system (Ga/x/In/1-x/Sb) have been investigated. Results indicate that GaP, InSb, GaSb, GaAs and possible AlP assume Metallic structures at high pressures; a tetragonal, beta-Sn-like structure is adopted by only InSb and GaSb. The rocksalt phase is preferred in InP, InAs, AlSb, ZnO and ZnS. The model of Van Vechten (1973) gives transition pressures which are in good agreement with measured values, but must be refined to account for the occurrence of the ionic rocksalt structure in some compounds. In addition, discrepancies between the theoretical scaling values for volume changes at the semiconductor-to-metal transitions are observed.

  4. 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

    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...... 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...... the safety of rolapitant as part of an antiemetic triple-drug regimen in patients receiving emetogenic chemotherapy, including those administered concomitant medications that are substrates of CYP2D6 or BCRP, such as ondansetron, docetaxel, or irinotecan....

  5. Nonisovalent Si-III-V and Si-II-VI alloys: Covalent, ionic, and mixed phases

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Joongoo; Park, Ji-Sang; Stradins, Pauls; Wei, Su-Huai

    2017-07-01

    Nonequilibrium growth of Si-III-V or Si-II-VI alloys is a promising approach to obtaining optically more active Si-based materials. We propose a new class of nonisovalent Si2AlP (or Si2ZnS) alloys in which the Al-P (or Zn-S) atomic chains are as densely packed as possible in the host Si matrix. As a hybrid of the lattice-matched parent phases, Si2AlP (or Si2ZnS) provides an ideal material system with tunable local chemical orders around Si atoms within the same composition and structural motif. Here, using first-principles hybrid functional calculations, we discuss how the local chemical orders affect the electronic and optical properties of the nonisovalent alloys.

  6. Contribution of capecitabine for therapy of patients with gastroesophageal cancer: an update of recent phase III results

    Directory of Open Access Journals (Sweden)

    Putao Cen

    2008-03-01

    Full Text Available Putao Cen, Eric D Tetzlaff, Jaffer A AjaniDepartment of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center, Houston, TX, USABackground: Capecitabine, an orally administered fluoropyrimidines, is widely used in the treatment of multiple malignancies. It has been extensively evaluated in patients with gastroesophageal carcinoma. Since recent reviews have discussed phase I/II trials (Cancer 107:221–231, 2006; Drugs 67:601–610, 2007, we focus on the impact of the results of the most current phase III trials using capectiabine in the treatment of advanced gastroesophageal cancers, primarily in the first-line setting.Methods: To find published phase III trials, Medline was searched for English-language clinical trials published from 1996 through June 2007 along with relevant abstracts presented at the American Society of Clinical Oncology, and meetings of the European Cancer Conference and European Society of Medical Oncology. Only representative trials were chosen for this manuscript.Results: The most frequently investigated combinations are capecitabine with taxanes, platinols, and camptothecins. Recent results of a large phase III trial (REAL-2 in untreated patients with gastroesophageal cancer suggest that capecitabine is a non-inferior substitute for intravenous 5-fluorouracil. These results of REAL-2 trial are substantiated by a smaller phase III trial. Previous analysis of multiple trials had suggested that capecitabine, when combined in doses lower than 1250 mg/m2 twice daily, consistently resulted in lower frequency of Grade 3 or 4 toxic effects.Conclusions: Capecitabine provides much needed convenience to patients with gastroesophageal cancer. The recent data derived from two phase III trials confirm that capecitabine is a suitable substitute for intravenous 5-fluorouracil in patients whose swallowing is not greatly affected. Capecitabine remains a subject of further

  7. Cobalt-60 heat source demonstration program. Phase III. Fabrication. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1973-06-01

    Significant accomplishments completed during Phase III of the /sup 60/Co Heat Source Demonstration program include the following: encapsulation of 2 MCi of /sup 60/Co; fabrication of the heat source, including the ASME coded pressure vessel/core assembly, and biological shielding; endurance testing of a prototype heat pipe for a period of 28 months; fabrication and qualification of the heat pipe emergency cooling subsystem; issue of the safety evaluation report, reference 3, and the operations manual, reference 4; and heat source assembly. The planned demonstration test program was modified to include testing of a total power system. Based on an evaluation of available power conversion systems, which included the closed-cycle Brayton and organic Rankine systems, the closed-cycle Brayton system was selected for use. Selection was based on advantages offered by the direct coupling of this conversion system with the gas-cooled heat source. In implementing the test program, the AiResearch BCD power conversion system was to be coupled to the heat source following initial heat source performance testing and part way through the endurance test. In accordance with the program redirection the following Phase IV checkout operations were completed to evaluate procedural and hardware acceptability: heat source dummy fueling; fueling cask sielding survey; and heat source shielding survey (single pin). Completion of these latter activities verified the acceptability of critical characteristics of the heat source and its supporting equipment.

  8. 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.

  9. Enrichment of dissimilatory Fe(III)-reducing bacteria from groundwater of the Siklós BTEX-contaminated site (Hungary).

    Science.gov (United States)

    Farkas, Milán; Szoboszlay, Sándor; Benedek, Tibor; Révész, Fruzsina; Veres, Péter Gábor; Kriszt, Balázs; Táncsics, András

    2017-01-01

    Dissimilatory iron-reducing bacteria are commonly found in microbial communities of aromatic hydrocarbon-contaminated subsurface environments where they often play key role in the degradation of the contaminants. The Siklós benzene, toluene, ethylbenzene, and xylene (BTEX)-contaminated area is one of the best characterized petroleum hydrocarbon-contaminated sites of Hungary. Continuous monitoring of the microbial community in the center of the contaminant plume indicated the presence of an emerging Geobacter population and a Rhodoferax phylotype highly associated with aromatic hydrocarbon-contaminated subsurface environments. The aim of the present study was to make an initial effort to enrich Rhodoferax-related and other dissimilatory iron-reducing bacteria from this environment. Accordingly, four slightly different freshwater media were used to enrich Fe(III) reducers, differing only in the form of nitrogen source (organic, inorganic nitrogen or gaseous headspace nitrogen). Although enrichment of the desired Rhodoferax phylotype was not succeeded, Geobacter-related bacteria were readily enriched. Moreover, the different nitrogen sources caused the enrichment of different Geobacter species. Investigation of the diversity of benzylsuccinate synthase gene both in the enrichments and in the initial groundwater sample indicated that the Geobacter population in the center of the contaminant plume may not play a significant role in the anaerobic degradation of toluene.

  10. Development and testing of commercial-scale, coal-fired combustion systems: Phase III. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    Based on studies that indicated a large potential for significantly increased coal-firing in the commercial sector, the U.S. Department of Energy`s Pittsburgh Energy Technology Center (PETC) sponsored a multi-phase development effort for advanced coal combustion systems. This Final Report presents the results of the last phase (Phase III) of a project for the development of an advanced coal-fired system for the commercial sector of the economy. The project performance goals for the system included dual-fuel capability (i.e., coal as primary fuel and natural gas as secondary fuel), combustion efficiency exceeding 99 percent, thermal efficiency greater than 80 percent, turndown of at least 3:1, dust-free and semi-automatic dry ash removal, fully automatic start-up with system purge and ignition verification, emissions performance exceeding New Source Performance Standards (NSPS) and approaching those produced by oil-fired, Commercial-sized units, and reliability, safety, operability, maintainability, and service life comparable to oil-fired units. The program also involved a site demonstration at a large facility owned by Striegel Supply Company, a portion of which was leased to MTCI. The site, mostly warehouse space, was completely unheated and the advanced coal-fired combustion system was designed and sized to heat this space. Three different coals were used in the project, one low and one high sulfur pulverized Pittsburgh No. 8 coal, and a micronized low volatile, bituminous coal. The sorbents used were Pfizer dolomitic limestone and an Anvil lime. More than 100 hours of screening test`s were performed to characterize the system. The parameters examined included coal firing rate, excess air level, ash recycle rate, coal type, dolomitic limestone feed rate, and steam injection rate. These tests indicated that some additional modifications for coal burning in the system were required.

  11. Development and testing of commercial-scale, coal-fired combustion systems: Phase III. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    Based on studies that indicated a large potential for significantly increased coal-firing in the commercial sector, the U.S. Department of Energy`s Pittsburgh Energy Technology Center (PETC) sponsored a multi-phase development effort for advanced coal combustion systems. This Final Report presents the results of the last phase (Phase III) of a project for the development of an advanced coal-fired system for the commercial sector of the economy. The project performance goals for the system included dual-fuel capability (i.e., coal as primary fuel and natural gas as secondary fuel), combustion efficiency exceeding 99 percent, thermal efficiency greater than 80 percent, turndown of at least 3:1, dust-free and semi-automatic dry ash removal, fully automatic start-up with system purge and ignition verification, emissions performance exceeding New Source Performance Standards (NSPS) and approaching those produced by oil-fired, Commercial-sized units, and reliability, safety, operability, maintainability, and service life comparable to oil-fired units. The program also involved a site demonstration at a large facility owned by Striegel Supply Company, a portion of which was leased to MTCI. The site, mostly warehouse space, was completely unheated and the advanced coal-fired combustion system was designed and sized to heat this space. Three different coals were used in the project, one low and one high sulfur pulverized Pittsburgh No. 8 coal, and a micronized low volatile, bituminous coal. The sorbents used were Pfizer dolomitic limestone and an Anvil lime. More than 100 hours of screening test`s were performed to characterize the system. The parameters examined included coal firing rate, excess air level, ash recycle rate, coal type, dolomitic limestone feed rate, and steam injection rate. These tests indicated that some additional modifications for coal burning in the system were required.

  12. 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

  13. Rapid method for determination of glyphosate in groundwater using high performance liquid chromatography and solid-phase extraction after derivatization

    Directory of Open Access Journals (Sweden)

    Valdir Eduardo Olivo

    2015-04-01

    Full Text Available The intensive use of pesticides in agriculture has prompted researchers to develop new methods for identifying these pollutants in water. This study sought to validate a high performance liquid chromatography (HPLC method to determine the concentration of the pesticide glyphosate in groundwater samples by using solid-phase extraction (SPE filters after derivatization with chloroformate 9-fluorenylmethoxycarbonyl (FMOC-Cl. For the HPLC method, we evaluated the following main validation parameters: linearity, specificity, precision, accuracy, robustness, and limits of detection and quantification. After validation of the method, we determined the concentration of glyphosate in samples from thirteen deep, tubular wells distributed in urban and rural areas in Chapecó, SC, Brazil. The solvent used in the extraction of excess FMOC-Cl was dichloromethane and subsequently filtration was performed on C18 SPE, and injected into the chromatograph column in amino polymer with fluorescence detection. The analytical curve made in ultrapure water was linear, with a correlation coefficient of 0.99. The limits of detection and quantification were 0.24 and 0.07 µg L-1, respectively. Recovery tests in natural waters ranged from 90.37 to 101.70%. Glyphosate was detected in 5 of the thirteen wells evaluated. The highest concentration of glyphosate (6.80 µg L-1 was detected in a countryside well, near the municipal water supply. Despite the low levels of glyphosate detected in our study, any amount present in groundwater samples is worrisome, as these molecules have low ground mobility.

  14. 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.

  15. Ten- to 15-year results of the Oxford Phase III mobile unicompartmental knee arthroplasty

    Science.gov (United States)

    Lisowski, L. A.; Meijer, L. I.; van den Bekerom, M. P. J.; Pilot, P.; Lisowski, A. E.

    2016-01-01

    Aims 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. Patients and Methods 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. Results 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. Conclusion 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. PMID:27694515

  16. Groundwater and surface-water interaction and effects of pumping in a complex glacial-sediment aquifer, phase 2, east-central Massachusetts

    Science.gov (United States)

    Eggleston, Jack R.; Zarriello, Phillip J.; Carlson, Carl S.

    2015-12-31

    The U.S. Geological Survey, in cooperation with the Town of Framingham, Massachusetts, has investigated the potential of proposed groundwater withdrawals at the Birch Road well site to affect nearby surface water bodies and wetlands, including Lake Cochituate, the Sudbury River, and the Great Meadows National Wildlife Refuge in east-central Massachusetts. In 2012, the U.S. Geological Survey developed a Phase 1 numerical groundwater model of a complex glacial-sediment aquifer to synthesize hydrogeologic information and simulate potential future pumping scenarios. The model was developed with MODFLOW-NWT, an updated version of a standard USGS numerical groundwater flow modeling program that improves solution of unconfined groundwater flow problems. The groundwater model and investigations of the aquifer improved understanding of groundwater–surface-water interaction and the effects of groundwater withdrawals on surface-water bodies and wetlands in the study area. The initial work also revealed a need for additional information and model refinements to better understand this complex aquifer system.

  17. 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...

  18. 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.

  19. Explorations of new phases in the Ga(III)/In(III)-Cu(II)-Se(IV)-O system.

    Science.gov (United States)

    Kong, Fang; Lin, Qi-Pu; Yi, Fei-Yan; Mao, Jiang-Gao

    2009-07-20

    Four new gallium(III)/indium(III), copper(II), selenium(IV) oxides, namely, Ga(2)Cu(SeO(3))(4) (1), Ga(2)CuO(SeO(3))(3) (2), and M(2)Cu(3)(SeO(3))(6) (M = Ga 3, In 4), have been synthesized by hydrothermal or high-temperature solid-state reactions. The structure of Ga(2)Cu(SeO(3))(4) (1) features a 2D layer of corner-sharing GaO(6) and CuO(6) octahedra with the SeO(3) groups hanging on both sides of the 2D layer. Ga(2)CuO(SeO(3))(3) (2) features a pillared layered structure in which the 1D Cu(SeO(3))(3)(4-) chains act as the pillars between 2D layers formed by corner- and edge-sharing GaO(n) (n = 4, 5) polyhedra. Although the chemical compositions of M(2)Cu(3)(SeO(3))(6) (M = Ga 3, In 4) are comparable, they belong to two different structural types. Ga(2)Cu(3)(SeO(3))(6) (3) exhibits a pillared layered structure built by [Ga(2)Cu(3)(SeO(3))(4)](4+) thick layers with Se(3)O(3)(2-) groups as pillars. The structure of In(2)Cu(3)(SeO(3))(6) (4) features a 3D network composed of [In(2)(SeO(3))(2)](2+) layers and [Cu(3)(SeO(3))(4)](2-) layers interconnected through Se-O-Cu and In-O-Cu bridges, exhibiting 8-MR helical tunnels along the a-axis. Results of magnetic property measurements indicate that there are considerable antiferromagnetic interactions between copper(II) centers in Ga(2)CuO(SeO(3))(3) (2) and M(2)Cu(3)(SeO(3))(6) (M = Ga 3, In 4). Interestingly, Ga(2)Cu(3)(SeO(3))(6) (3) behaves as a weak ferromagnet below the critical temperature of T(c) = 15 K. Further magnetic studies indicate that the compound is a canted antiferromagnet with a large canting angle of about 7.1 degrees.

  20. IMPROVEMENT TO PIPELINE COMPRESSOR ENGINE RELIABILITY THROUGH RETROFIT MICRO-PILOT IGNITION SYSTEM -- PHASE III

    Energy Technology Data Exchange (ETDEWEB)

    Scott Chase; Daniel Olsen; Ted Bestor

    2005-03-01

    This report documents the third year's effort towards a 3-year program conducted by the Engines & Energy Conversion Laboratory (EECL) at Colorado State University (CSU) to develop micropilot ignition systems for existing pipeline compressor engines. Research activities for the overall program were conducted with the understanding that the efforts are to result in a commercial product to capture and disseminate the efficiency and environmental benefits of this new technology. Commercially-available fuel injection products were identified and applied to the program where appropriate. This approach will minimize the overall time-to-market requirements, while meeting performance and cost criteria. Two earlier phases of development precede this report. The objective for Phase I was to demonstrate the feasibility of retrofit micropilot ignition (RMI) systems for large bore, slow speed engines operating at low compression ratios under laboratory conditions at the EECL. The objective for Phase II was to further develop and optimize the micropilot ignition system at the EECL for large bore, slow speed engines operating at low compression ratios. These laboratory results were enhanced, then verified via a field demonstration project during Phase III of the Micropilot Ignition program. An Implementation Team of qualified engine retrofit service providers was assembled to install the retrofit micropilot ignition system for an engine operated by El Paso Pipeline Group at a compressor station near Window Rock, Arizona. Testing of this demonstration unit showed that the same benefits identified by laboratory testing at CSU, i.e., reduced fuel consumption and exhaust emissions (NOx, THC, CO, and CH2O). Installation efforts at Window Rock were completed towards the end of the budget period, which did not leave sufficient time to complete the durability testing. These efforts are ongoing, with funding provided by El Paso Pipeline Group, and the results will be documented in a

  1. Phase-transformation-induced twinning of an iron(III) calix[4]pyrrolidine complex.

    Science.gov (United States)

    Journot, Guillaume; Neier, Reinhard; Stoeckli-Evans, Helen

    2014-07-01

    The title compound, tetrachlorido-1κCl;2κ(3)Cl-(2,2,7,7,12,12,17,17-octamethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1(3,6).1(8,11).1(13,16)]tetracosane-1κ(4)N,N',N'',N''')-μ2-oxido-diiron(III), [Fe2Cl4O(C28H52N4)], undergoes a slow phase transformation at ca 173 K from monoclinic space group P2(1)/n, denoted form (I), to the maximal non-isomorphic subgroup, triclinic space group P1, denoted form (II), which is accompanied by nonmerohedral twinning [twin fractions of 0.693 (4) and 0.307 (4)]. The transformation was found to be reversible, as on raising the temperature the crystal reverted to monoclinic form (I). In the asymmetric unit of form (I), Z' = 1, while in form (II), Z' = 2, with a very small reduction (ca 1.8%) in the unit-cell volume. The two independent molecules (A and B) in form (II) are related by a pseudo-twofold screw axis along the b axis. The molecular overlay of molecule A on molecule B has an r.m.s. deviation of 0.353 Å, with the largest distance between two equivalent atoms being 1.202 Å. The reaction of calix[4]pyrrolidine, the fully reduced form of meso-octamethylporphyrinogen, with FeCl3 gave a red-brown solid that was recrystallized from ethanol in air, resulting in the formation of the title compound. In both forms, (I) and (II), the Fe(III) atoms are coordinated to the macrocyclic ligand and have distorted octahedral FeN4OCl coordination spheres. These Fe(III) atoms lie out of the mean plane of the four N atoms, displaced towards the O atom of the [OFeCl3] unit by 0.2265 (5) Å in form (I), and by 0.2210 (14) and 0.2089 (14) Å, respectively, in the two independent molecules (A and B) of form (II). The geometry of the [OFeCl3] units are similar, with each Fe(III) atom having a tetrahedral coordination sphere. The NH H atoms are directed below the planes of the macrocycles and are hydrogen bonded to the coordinated Cl(-) ions. There are also intramolecular C-H···Cl hydrogen bonds present in both (I) and (II

  2. 234U/238U isotope data from groundwater and solid-phase leachate samples near Tuba City Open Dump, Tuba City, Arizona

    Science.gov (United States)

    Johnson, Raymond H.; Horton, Robert J.; Otton, James K.; Ketterer, Michael K.

    2012-01-01

    This report releases 234U/238U isotope data, expressed as activity ratios, and uranium concentration data from analyses completed at Northern Arizona University for groundwater and solid-phase leachate samples that were collected in and around Tuba City Open Dump, Tuba City, Arizona, in 2008.

  3. 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.

  4. Intensified Adjuvant Treatment of Prostate Carcinoma: Feasibility Analysis of a Phase I/II Trial

    Science.gov (United States)

    Mantini, Giovanna; Fersino, Sergio; Frascino, Vincenzo; Massaccesi, Mariangela; Fionda, Bruno; Luzi, Stefano; Balducci, Mario; De Belvis, Antonio; Morganti, Alessio Giuseppe; Valentini, Vincenzo

    2014-01-01

    Purpose. To perform a preliminary feasibility acute and late toxicity evaluation of an intensified and modulated adjuvant treatment in prostate cancer (PCa) patients after radical prostatectomy. Material and Methods. A phase I/II has been designed. Eligible patients were 79 years old or younger, with an ECOG of 0–2, previously untreated, histologically proven prostate adenocarcinoma with no distant metastases, pT2–4 N0-1, and with at least one of the following risk factors: capsular perforation, positive surgical margins, and seminal vesicle invasion. All patients received a minimum dose on tumor bed of 64.8 Gy, or higher dose (70.2 Gy; 85.4%), according to the pathological stage, pelvic lymph nodes irradiation (57.7%), and/or hormonal therapy (69.1%). Results. 123 patients were enrolled and completed the planned treatment, with good tolerance. Median follow-up was 50.6 months. Grade 3 acute toxicity was only 2.4% and 3.3% for genitourinary (GU) and gastrointestinal (GI) tract, respectively. No patient had late grade 3 GI toxicity, and the GU grade 3 toxicity incidence was 5.8% at 5 years. 5-year BDSF was 90.2%. Conclusions. A modulated and intensified adjuvant treatment in PCa was feasible in this trial. A further period of observation can provide a complete assessment of late toxicity and confirm the BDSF positive results. PMID:25093169

  5. Solid Phase Extraction for Monitoring of Occupational Exposure to Cr (III

    Directory of Open Access Journals (Sweden)

    S.J. Shahtaheri

    2007-01-01

    Full Text Available Chromium is an important constituent widely used in different industrial processes for production of various synthetic materials. For evaluation of workers’ exposure to trace toxic metal of Cr (III, environmental and biological monitoring are essential processes, in which, preparation of samples is one of the most time-consuming and error-prone aspects prior to analysis. The use of solid-phase extraction (SPE has grown and is a fertile technique of sample preparation as it provides better results than those produced by liquid-liquid extraction (LLE. SPE using mini columns filled with XAD-4 resin was optimized regarding to sample pH, ligand concentration, loading flow rate, elution solvent, sample volume, elution volume, amount of resins, and sample matrix interferences. Chromium was retained on solid sorbent and was eluted with 2 M HNO3 followed by simple determination of analytes by using flame atomic absorption spectrometery. Obtained recoveries of metal ion were more than 92%. The optimized procedure was also validated with three different pools of spiked urine samples and showed a good reproducibility over six consecutive days as well as six within-day experiments. Through this study, suitable results were obtained for relative standard deviation, therefore, it is concluded that, this optimized method can be considered to be successful in simplifying sample preparation for trace residue analysis of Cr in different matrices for evaluation of occupational and environmental exposures. To evaluate occupational exposure to chromium, 16 urine samples were taken, prepared, and analyzed based on optimized procedure.

  6. 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...... using EDSS was -31 % [hazard ratio (HR) 0.69, p = 0.063], and using Multiple Sclerosis Functional Composite (MSFC) z-score was -77 % (p = 0.150), vs. placebo. IFNβ-1a reduced ARR 26 % (RR = 0.74, 95 % CI 0.60-0.92, p = 0.007), showed no effect on PBVC loss (+11 %, p = 0.14), and changes in disability...... worsening were -26 and -66 % as measured using the EDSS (HR 0.742, p = 0.13) and MSFC (p = 0.208), respectively. Adverse events occurred in 75, 82, and 70 % of laquinimod, IFNβ-1a, and placebo patients, respectively. Once-daily oral laquinimod 0.6 mg resulted in statistically nonsignificant reductions...

  7. Epitaxial growth of three dimensionally structured III-V photonic crystal via hydride vapor phase epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Qiye; Kim, Honggyu; Zhang, Runyu; Zuo, Jianmin; Braun, Paul V., E-mail: pbraun@illinois.edu [Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Sardela, Mauro [Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Balaji, Manavaimaran; Lourdudoss, Sebastian; Sun, Yan-Ting [Laboratory of Semiconductor Materials, Department of Materials and Nano Physics, Royal Institute of Technology (KTH), Electrum 229, 164 40 Kista (Sweden)

    2015-12-14

    Three-dimensional (3D) photonic crystals are one class of materials where epitaxy, and the resultant attractive electronic properties, would enable new functionalities for optoelectronic devices. Here we utilize self-assembled colloidal templates to fabricate epitaxially grown single crystal 3D mesostructured Ga{sub x}In{sub 1−x}P (GaInP) semiconductor photonic crystals using hydride vapor phase epitaxy (HVPE). The epitaxial relationship between the 3D GaInP and the substrate is preserved during the growth through the complex geometry of the template as confirmed by X-ray diffraction (XRD) and high resolution transmission electron microscopy. XRD reciprocal space mapping of the 3D epitaxial layer further demonstrates the film to be nearly fully relaxed with a negligible strain gradient. Fourier transform infrared spectroscopy reflection measurement indicates the optical properties of the photonic crystal which agree with finite difference time domain simulations. This work extends the scope of the very few known methods for the fabrication of epitaxial III-V 3D mesostructured materials to the well-developed HVPE technique.

  8. Intensified Adjuvant Treatment of Prostate Carcinoma: Feasibility Analysis of a Phase I/II Trial

    Directory of Open Access Journals (Sweden)

    Giovanna Mantini

    2014-01-01

    Full Text Available Purpose. To perform a preliminary feasibility acute and late toxicity evaluation of an intensified and modulated adjuvant treatment in prostate cancer (PCa patients after radical prostatectomy. Material and Methods. A phase I/II has been designed. Eligible patients were 79 years old or younger, with an ECOG of 0–2, previously untreated, histologically proven prostate adenocarcinoma with no distant metastases, pT2–4 N0-1, and with at least one of the following risk factors: capsular perforation, positive surgical margins, and seminal vesicle invasion. All patients received a minimum dose on tumor bed of 64.8 Gy, or higher dose (70.2 Gy; 85.4%, according to the pathological stage, pelvic lymph nodes irradiation (57.7%, and/or hormonal therapy (69.1%. Results. 123 patients were enrolled and completed the planned treatment, with good tolerance. Median follow-up was 50.6 months. Grade 3 acute toxicity was only 2.4% and 3.3% for genitourinary (GU and gastrointestinal (GI tract, respectively. No patient had late grade 3 GI toxicity, and the GU grade 3 toxicity incidence was 5.8% at 5 years. 5-year BDSF was 90.2%. Conclusions. A modulated and intensified adjuvant treatment in PCa was feasible in this trial. A further period of observation can provide a complete assessment of late toxicity and confirm the BDSF positive results.

  9. Phase II Groundwater Flow Model of Corrective Action Unit 98: Frenchman Flat, Nevada Test Site, Nye County, Nevada, Rev. No.: 0

    Energy Technology Data Exchange (ETDEWEB)

    John McCord

    2006-05-01

    The Phase II Frenchman Flat groundwater flow model is a key element in the ''Federal Facility Agreement and Consent Order'' (FFACO) (1996) corrective action strategy for the Underground Test Area (UGTA) Frenchman Flat corrective action unit (CAU). The objective of this integrated process is to provide an estimate of the vertical and horizontal extent of contaminant migration for each CAU to predict contaminant boundaries. A contaminant boundary is the model-predicted perimeter that defines the extent of radionuclide-contaminated groundwater from underground testing above background conditions exceeding the ''Safe Drinking Water Act'' (SDWA) standards. The contaminant boundary will be composed of both a perimeter boundary and a lower hydrostratigraphic unit (HSU) boundary. The computer model will predict the location of this boundary within 1,000 years and must do so at a 95 percent level of confidence. Additional results showing contaminant concentrations and the location of the contaminant boundary at selected times will also be presented. These times may include the verification period, the end of the five-year proof-of-concept period, as well as other times that are of specific interest. This report documents the development and implementation of the groundwater flow model for the Frenchman Flat CAU. Specific objectives of the Phase II Frenchman Flat flow model are to: (1) Incorporate pertinent information and lessons learned from the Phase I Frenchman Flat CAU models. (2) Develop a three-dimensional (3-D), mathematical flow model that incorporates the important physical features of the flow system and honors CAU-specific data and information. (3) Simulate the steady-state groundwater flow system to determine the direction and magnitude of groundwater fluxes based on calibration to Frenchman Flat hydrogeologic data. (4) Quantify the uncertainty in the direction and magnitude of groundwater flow due to uncertainty in

  10. NOVEL CONCEPTS FOR THE COMPRESSION OF LARGE VOLUMES OF CARBON DIOXIDE-PHASE III

    Energy Technology Data Exchange (ETDEWEB)

    Moore, J. Jeffrey; Allison, Timothy; Evans, Neal; Moreland, Brian; Hernandez, Augusto; Day, Meera; Ridens, Brandon

    2014-06-30

    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.

  11. AG Carinae III. The 1990 hot phase of the star and the physical structure of the circumstellar environment

    CERN Document Server

    Viotti, R; Rossi, C

    1993-01-01

    Long slit spectra of the region around the Luminous Blue Variable AG Car obtained in June 1990, just before the onset of its new brightening phase, indicate that AG Car was in the hottest phase so far recorded. The spectrum shows strong broad emissions of He II 468.6 nm, and [Fe III] 465.8-470.1 nm, and He I, N II, Si III, Al III and Fe III with a P Cygni profile. We have also identified weak lines of C II and O II. A faint continuum emission has been detected within the whole ring nebula. We also find that the spectrum of some regions is partially due to scattered star's light. This provides evidence of the presence of dust grains, and indicates that even in present times dust is condensing from AG Car wind. The sharp outer edge of the ring suggest the presence of a shock front. We have also identified an extended low density H II $halo$, which should be associated with the residual of the stellar wind of a previous cooler evolutionary phase of AG Car. In the halo the H$\\alpha$/[N II] ratio is strengthened w...

  12. Physician refer thyself: is Stark II, phase III the final voyage?

    Science.gov (United States)

    Manchikanti, Laxmaiah; McMahon, Erin Brisbay

    2007-11-01

    , the Stark I prohibition on self-referrals by physicians expanded to include 10 additional healthcare services known as designated health services or DHS. The 1993 expansion of Stark I was enacted in 1995 as Stark II. In 2007, CMS adopted Phase III of the regulations interpreting Stark II. Phase III made multiple changes and clarified many previous issues, and it becomes effective December 4, 2007. While it is mandatory to obtain expert legal advice and this manuscript in no way provides the extensive navigation required through the maze of Stark laws and other anti-kickback statutes, it is incumbent on interventionalists in all settings of practice to have appropriate knowledge of the Stark laws and exceptions and of the anti-kickback statute and safe harbors. Penalties for violating the Stark laws are severe, including fines of up to dollars 15,000 per service and the economic threat of exclusion from participation in federal healthcare programs, which may result in exclusion of any type of healthcare program and loss of privileges at hospitals and surgery centers. This manuscript reviews physician practices in general, physician payments, and self-referral patterns in particular, the evolution of the Stark law and regulations and its implications for physician practices. This article is not, and should not be, construed as legal advice or an opinion on specific situations.

  13. Temozolomide combined with irradiation as postoperative treatment of primary glioblastoma multiforme. Phase I/II study

    Energy Technology Data Exchange (ETDEWEB)

    Combs, S.E.; Gutwein, S.; Schulz-Ertner, D.; Thilmann, C.; Wannenmacher, M.M.; Debus, J. [Dept. of Radiation Oncology, Univ. of Heidelberg, Heidelberg (Germany); Kampen, M. van [Dept. of Radiation Oncology, Nordwestkrankenhaus Frankfurt, Frankfurt/Main (Germany); Edler, L. [Central Unit Biostatistics, German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2005-06-01

    Background and purpose: the role of radiochemotherapy in the treatment of primary glioblastoma multiforme is still discussed controversially. To evaluate the feasibility and toxicity of irradiation and concomitant administration of 50 mg/m{sup 2} temozolomide in patients with primary malignant glioma, this phase I/II study was conducted. Patients and methods: 53 patients with histologically confirmed WHO grade IV malignant glioma were enrolled into the study. All patients were treated with radiation therapy up to a total dose of 60 Gy using conventional fractionation of 5 x 2.0 Gy/week. Temozolomide was administered orally each therapy day at a dose of 50 mg/m{sup 2}. Results: prior to radiochemotherapy, complete resection (n = 14), subtotal resection (n = 22) or a biopsy (n = 17) of the tumor was performed. The median time interval between surgery and radiochemotherapy was 21 days. Treatment-related toxicity was very mild. Acute toxicity > grade 2 was observed in one patient who developed grade 4 hemotoxicity. Minor side effects of chemotherapy included nausea and vomiting. No severe late effects were observed. Median progression-free and overall survival were 8 and 19 months, respectively. The overall survival rate was 72% at 1 and 26% at 2 years. Age and extent of surgery significantly influenced survival. Conclusion: the combination of temozolomide plus radiation therapy is feasible and safe in terms of toxicity. Overall survival times were relatively long compared to survival times reported for radiotherapy alone. The application of 50 mg/m{sup 2} of temozolomide can be performed throughout the whole time course without interruption due to side effects and might largely contribute to the prolonged overall survival. Further evaluation is warranted as to which dose of temozolomide is optimal with regard to tumor response and toxicity. (orig.)

  14. Phase III randomized trial of toremifene versus tamoxifen for Japanese postmenopausal patients with early breast cancer.

    Science.gov (United States)

    Kimura, Morihiko; Tominaga, Takeshi; Kimijima, Izo; Takatsuka, Yuichi; Takashima, Shigemitsu; Nomura, Yasuo; Kasumi, Fujio; Yamaguchi, Akihiro; Masuda, Norikazu; Noguchi, Shinzaburo; Eshima, Nobuoki

    2014-05-01

    Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen. The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events. A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated. Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.

  15. Genomic Scans of Zygotic Disequilibrium and Epistatic SNPs in HapMap Phase III Populations.

    Directory of Open Access Journals (Sweden)

    Xin-Sheng Hu

    Full Text Available Previous theory indicates that zygotic linkage disequilibrium (LD is more informative than gametic or composite digenic LD in revealing natural population history. Further, the difference between the composite digenic and maximum zygotic LDs can be used to detect epistatic selection for fitness. Here we corroborate the theory by investigating genome-wide zygotic LDs in HapMap phase III human populations. Results show that non-Africa populations have much more significant zygotic LDs than do Africa populations. Africa populations (ASW, LWK, MKK, and YRI possess more significant zygotic LDs for the double-homozygotes (DAABB than any other significant zygotic LDs (DAABb, DAaBB, and DAaBb, while non-Africa populations generally have more significant DAaBb's than any other significant zygotic LDs (DAABB, DAABb, and DAaBB. Average r-squares for any significant zygotic LDs increase generally in an order of populations YRI, MKK, CEU, CHB, LWK, JPT, CHD, TSI, GIH, ASW, and MEX. Average r-squares are greater for DAABB and DAaBb than for DAaBB and DAABb in each population. YRI and MKK can be separated from LWK and ASW in terms of the pattern of average r-squares. All population divergences in zygotic LDs can be interpreted with the model of Out of Africa for modern human origins. We have also detected 19735-95921 SNP pairs exhibiting strong signals of epistatic selection in different populations. Gene-gene interactions for some epistatic SNP pairs are evident from empirical findings, but many more epistatic SNP pairs await evidence. Common epistatic SNP pairs rarely exist among all populations, but exist in distinct regions (Africa, Europe, and East Asia, which helps to understand geographical genomic medicine.

  16. Phylodynamics of HIV-1 from a phase III AIDS vaccine trial in Bangkok, Thailand.

    Directory of Open Access Journals (Sweden)

    Marcos Pérez-Losada

    Full Text Available BACKGROUND: In 2003, a phase III placebo-controlled trial (VAX003 was completed in Bangkok, Thailand. Of the 2,546 individuals enrolled in the trial based on high risk for infection through injection drug use (IDU, we obtained clinical samples and HIV-1 sequence data (envelope glycoprotein gene gp120 from 215 individuals who became infected during the trial. Here, we used these data in combination with other publicly available gp120 sequences to perform a molecular surveillance and phylodynamic analysis of HIV-1 in Thailand. METHODOLOGY AND FINDINGS: Phylogenetic and population genetic estimators were used to assess HIV-1 gp120 diversity as a function of vaccination treatment, viral load (VL and CD4(+ counts, to identify transmission clusters and to investigate the timescale and demographics of HIV-1 in Thailand. Three HIV-1 subtypes were identified: CRF01_AE (85% of the infections, subtype B (13% and CRF15_AE (2%. The Bangkok IDU cohort showed more gp120 diversity than other Asian IDU cohorts and similar diversity to that observed in sexually infected individuals. Moreover, significant differences (P<0.02 in genetic diversity were observed in CRF01_AE IDU with different VL and CD4(+ counts. No phylogenetic structure was detected regarding any of the epidemiological and clinical factors tested, although high proportions (35% to 50% of early infections fell into clusters, which suggests that transmission chains associated with acute infection play a key role on HIV-1 spread among IDU. CRF01_AE was estimated to have emerged in Thailand in 1984.5 (1983-1986, 3-6 years before the first recognition of symptomatic patients (1989. The relative genetic diversity of the HIV-1 population has remained high despite decreasing prevalence rates since the mid 1990s. CONCLUSIONS: Our study and recent epidemiological reports indicate that HIV-1 is still a major threat in Thailand and suggest that HIV awareness and prevention needs to be strengthened to avoid

  17. Efficient formation of luminescent lanthanide(III) complexes by solid-phase synthesis and on-resin screening.

    Science.gov (United States)

    Nakamura, Tatsuya; Mizukami, Shin; Tanaka, Miho; Kikuchi, Kazuya

    2013-11-01

    Time-resolved luminescence measurements of luminescent lanthanide complexes have advantages in biological assays and high-throughput screening, owing to their high sensitivity. In spite of the recent advances in their energy-transfer mechanism and molecular-orbital-based computational molecular design, it is still difficult to estimate the quantum yields of new luminescent lanthanide complexes. Herein, solid-phase libraries of luminescent lanthanide complexes were prepared through amide-condensation and Pd-catalyzed coupling reactions and their luminescent properties were screened with a microplate reader. Good correlation was observed between the time-resolved luminescence intensities of the solid-phase libraries and those of the corresponding complexes that were synthesized by using liquid-phase chemistry. This method enabled the rapid and efficient development of new sensitizers for Sm(III), Eu(III), and Tb(III) luminescence. Thus, solid-phase combinatorial synthesis combined with on-resin screening led to the discovery of a wide variety of luminescent sensitizers.

  18. Solid phase extraction of gold(III) on Amberlite XAD-2000 prior to its flame atomic absorption spectrometric determination.

    Science.gov (United States)

    Elci, Latif; Sahan, Derya; Basaran, Aydan; Soylak, Mustafa

    2007-09-01

    A solid phase extraction method for the determination of gold(III) at trace levels by flame atomic absorption spectrometer (FAAS) was developed. The method was based on retention of gold as chloro complexes through the Amberlite XAD-2000. The effect of some analytical parameters including hydrochloric acid concentration, sample volume, sample and eluent flow rates, eluent volume, eluent concentration and interfering ions on the recovery of gold(III) was investigated. The retention of gold(III) from 1.5 mol l(-1) HCl solution and the recovery of gold with 0.07 mol l(-1) NH3 solution were quantitative (>or=95%). The relative standard deviation (RSD) was calculated as 3.2% (n = 10). The detection limit for gold was 2 microg l(-1). The accuracy was checked with the determination of gold spiked an artificial seawater and a pure copper samples.

  19. Predicting Pattern Tooling and Casting Dimensions for Investment Casting, Phase III

    Energy Technology Data Exchange (ETDEWEB)

    Sabau, Adrian S [ORNL

    2008-04-01

    Efforts during Phase III focused mainly on the shell-alloy systems. A high melting point alloy, 17-4PH stainless steel, was considered. The experimental part of the program was conducted at ORNL and commercial foundries, where wax patterns were injected, molds were invested, and alloys were poured. Shell molds made of fused-silica and alumino-silicates were considered. A literature review was conducted on thermophysical and thermomechanical properties alumino-silicates. Material property data, which were not available from material suppliers, was obtained. For all the properties of 17-4PH stainless steel, the experimental data available in the literature did not cover the entire temperature range necessary for process simulation. Thus, some material properties were evaluated using ProCAST, based on CompuTherm database. A comparison between the predicted material property data and measured property data was made. It was found that most material properties were accurately predicted only over several temperature ranges. No experimental data for plastic modulus were found. Thus, several assumptions were made and ProCAST recommendations were followed in order to obtain a complete set of mechanical property data at high temperatures. Thermal expansion measurements for the 17-4PH alloy were conducted during heating and cooling. As a function of temperature, the thermal expansion for both the alloy and shell mold materials showed different evolution on heating and cooling. Numerical simulations were performed using ProCAST for the investment casting of 17-4PH stainless steel parts in fused silica molds using the thermal expansion obtained on heating and another one with thermal expansion obtained on cooling. Since the fused silica shells had the lowest thermal expansion properties in the industry, the dewaxing phase, including the coupling between wax-shell systems, was neglected. The shell mold was considered to be a pure elastic material. The alloy dimensions were

  20. 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.

  1. Iron (III oxide fabrication from natural clay with reference to phase transformation γ- → α-Fe2O3

    Directory of Open Access Journals (Sweden)

    Šaponjić Aleksandra

    2017-01-01

    Full Text Available Amorphous iron (III oxide was obtained from clay, using ammonium hydroxide as a precipitating agent. Influence of freeze drying under vacuum, as a drying method, on particle size, chemical composition, and crystallinity of obtained iron (III oxide powder was investigated. After freeze drying, precipitate was annealed in air at 500°C and 900°C. X-ray diffraction, particle size analysis, scanning electron microscopy, energy dispersive spectrometry, Fourier transform infrared spectroscopy, thermogravimetric and differential thermal analysis were used to characterize obtained iron (III oxide powder. All of three powders obtained by freeze drying and annealing, have low crystallinity and particles with irregular layered shape. Narrow particle size distribution was given by an average diameter value of around 50 μm for all observed powders. Iron-bearing materials like α-Fe2O3 and γ- Fe2O3 are obtained. Differential thermal analysis curve of obtained samples showed endothermic reaction at 620°C which could be ascribed to phase transition from cubic form γ- → α- Fe2O3. Thermal transformations of iron (III oxide, obtained from clay as a natural source, is suitable to explore in the framework of materials chemistry, and opens the possibility to synthesize materials based on Fe2O3 with specific magnetic behavior. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III-45012, Grant no. OI-172045, Grant no. III-45015, Grant no. OI-176010, Grant no. OI-172056 and Grant no. III-45007

  2. 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

  3. Design and analysis of phase III trials with ordered outcome scales: the concept of the sliding dichotomy.

    Science.gov (United States)

    Murray, Gordon D; Barer, David; Choi, Sung; Fernandes, Helen; Gregson, Barbara; Lees, Kennedy R; Maas, Andrew I R; Marmarou, Anthony; Mendelow, A David; Steyerberg, Ewout W; Taylor, Gillian S; Teasdale, Graham M; Weir, Christopher J

    2005-05-01

    The conventional approach to the analysis of a Phase III trial in head injury or stroke takes an ordered scale measuring functional outcome and collapses the scale to a binary outcome of favorable versus unfavorable. This discards potentially relevant information which limits statistical power and moreover is not in accord with clinical practice. We propose an alternative approach where a favorable outcome is defined as better than would be expected, taking account of each individual patient's baseline prognosis. This is illustrated through a worked example based on data from a Phase III trial in head injury. The approach is also compared with the proportional odds model, which is another statistical approach that can exploit an ordered outcome scale. The approach raises issues of clinical, statistical, and regulatory importance, and we initiate what we believe needs to become a widespread debate amongst the community involved in clinical research in head injury and stroke.

  4. 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.

  5. Phase fluctuation spectra: New radio science information to become available in the DSN tracking system Mark III-77

    Science.gov (United States)

    Berman, A. L.

    1977-01-01

    An algorithm was developed for the continuous and automatic computation of Doppler noise concurrently at four sample rate intervals, evenly spanning three orders of magnitude. Average temporal Doppler phase fluctuation spectra will be routinely available in the DSN tracking system Mark III-77 and require little additional processing. The basic (noise) data will be extracted from the archival tracking data file (ATDF) of the tracking data management system.

  6. Environmental mobility of cobalt-Influence of solid phase characteristics and groundwater chemistry.

    Science.gov (United States)

    Payne, T E; Itakura, T; Comarmond, M J; Harrison, J J

    2009-01-01

    The adsorption of cobalt on samples from a potential waste repository site in an arid region was investigated in batch experiments, as a function of various solution phase parameters including the pH and ionic strength. The samples were characterized using a range of techniques, including BET surface area measurements, total clay content and quantitative X-ray diffraction. The statistical relationships between the measured cobalt distribution coefficients (K(d) values) and the solid and liquid phase characteristics were assessed. The sorption of cobalt increased with the pH of the aqueous phase. In experiments with a fixed pH value, the measured K(d) values were strongly correlated to the BET surface area, but not to the amount of individual clay minerals (illite, kaolinite or smectite). A further set of sorption experiments was undertaken with two samples of distinctive mineralogy and surface area, and consequently different sorption properties. A simple surface complexation model (SCM) that conceptualized the surface sites as having equivalent sorption properties to amorphous Fe-oxide was moderately successful in explaining the pH dependence of the sorption data on these samples. Two different methods of quantifying the input parameters for the SCM were assessed. While a full SCM for cobalt sorption on these complex environmental substrates is not yet possible, the basic applicability and predictive capability of this type of modeling is demonstrated. A principal requirement to further develop the modeling approach is adequate models for cobalt sorption on component mineral phases of complex environmental sorbents.

  7. Groundwater cleanup by in-situ sparging. IX. Air channeling model for nonaqueous phase liquid removal

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, D.J.; Norris, R.D.; Clarke, A.N. [Eckenfelder, Inc., Nashville, TN (United States)

    1996-04-01

    A mathematical model is developed to simulate the removal of dissolved and nonaqueous phase liquid (NAPL) volatile organic compounds (VOCs) from contaminated aquifers by sparging. The model assumes that the sparging air moves through the aquifer in persistent channels and that NAPL must dissolve and move to these channels by diffusion and dispersion processes. The dependence of the model results on model parameters is explored, and practical implications for sparging well operation are discussed.

  8. Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program.

    Directory of Open Access Journals (Sweden)

    Paul Emery

    Full Text Available The objective was to determine the safety of ocrelizumab (OCR in patients with rheumatoid arthritis (RA.This was an analysis of the double-blind, placebo-controlled periods and long-term follow-up of 4 OCR phase III trials in RA (SCRIPT, STAGE, FILM and FEATURE. Safety data per study and the results of a meta-analysis of serious infectious events (SIEs are presented.Overall, 868 patients received placebo, 1064 patients OCR 200 mg×2 (or 400 mg×1 (OCR200, and 827 patients OCR 500 mg×2 (OCR500 plus background methotrexate (MTX at baseline and 24 weeks. During the double-blind, placebo-controlled periods, the incidence of adverse events and serious adverse events was comparable between the OCR+MTX and placebo +MTX groups. Infusion-related reactions were more common with OCR+MTX and decreased in frequency with subsequent infusions. Serious infusion-related reactions were rare (0.1%. Serious infections occurred more frequently with OCR500+MTX. In the meta-analysis, a statistically significant difference from placebo +MTX in incidence of SIEs per 100 patient-years of 2.4 (95% CI, 0.3-4.5 was observed with OCR500+MTX, but not with OCR200+MTX (0.6; 95% CI, -1.3 to 2.4. Patients recruited in Asia exhibited a higher risk of serious infections (hazard ratio, 1.78; 95% CI, 1.03-3.06. The incidence of human anti-human antibodies was <5%. Long-term follow-up indicated no differences in malignancy rates between the treatment groups. There was no apparent difference in time to B-cell repletion between the OCR dose groups.In placebo-controlled clinical trials of RA, OCR500+MTX was associated with a higher risk of serious infections compared with placebo +MTX. The safety profile of OCR 200+MTX was comparable with placebo+MTX.STAGE ClinicalTrials.gov NCT00406419 SCRIPT ClinicalTrials.gov NCT00476996 FILM ClinicalTrials.gov NCT00485589 FEATURE ClinicalTrials.gov NCT00673920.

  9. Fe doped TiO{sub 2} photocatalyst for the removal of As(III) under visible radiation and its potential application on the treatment of As-contaminated groundwater

    Energy Technology Data Exchange (ETDEWEB)

    Garza-Arévalo, J.I.; García-Montes, I. [Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Químicas, Cd. Universitaria, San Nicolás de los Garza, Nuevo León C.P. 66451, México (Mexico); Reyes, M.Hinojosa [Instituto Potosino de Investigación Científica y Tecnológica, IPICYT, División de Materiales Avanzados, Camino a la Presa San José 2055, Col. Lomas 4a. sección, San Luis Potosí, SLP 78216, México (Mexico); Guzmán-Mar, J.L. [Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Químicas, Cd. Universitaria, San Nicolás de los Garza, Nuevo León C.P. 66451, México (Mexico); Rodríguez-González, V. [Instituto Potosino de Investigación Científica y Tecnológica, IPICYT, División de Materiales Avanzados, Camino a la Presa San José 2055, Col. Lomas 4a. sección, San Luis Potosí, SLP 78216, México (Mexico); and others

    2016-01-15

    Highlights: • Incorporation of Fe in TiO{sub 2} lattice extended absorption to visible light region. • TiO{sub 2}–Fe 1.0 in anatase crystalline form was synthesized by sol–gel method. • TiO{sub 2}–Fe 1.0 showed the highest photocatalytic activity for As(III) oxidation. • TiO{sub 2}–Fe 1.0 had the highest adsorption capacity for the removal of generated As(V). • TiO{sub 2}–Fe is a promising material on the treatment of As contaminated groundwater. - Abstract: The Fe doped TiO{sub 2} catalyst was evaluated under visible radiation for As(III) removal. The TiO{sub 2}–Fe was synthesized by sol–gel technique at 0.0, 1.0, 2.5, 5.0 and 10.0 wt% iron doping concentrations. The semiconductors were characterized by X-ray diffraction, diffuse reflectance UV–vis, Raman spectroscopy, nitrogen physisorption, SEM–EDS and potentiometric titration for point of zero charge determination. The photocatalytic oxidation of As(III) was assessed in aqueous suspension contained 5 mg L{sup −1} As(III) at pH 7 with 0.25 g L{sup −1} catalyst loading. The incorporation of iron ions in TiO{sub 2} lattice extended the absorption to visible light region and create surface oxygen vacancies which favor photocatalytic oxidation reaction of As(III) using a small doping amount of Fe (1.0 wt%) in TiO{sub 2} powder. Additionally, TiO{sub 2}–Fe 1.0 showed the highest adsorption capacity for As(V) removal compared to sol–gel TiO{sub 2} and P25 indicating that this catalyst is a promising material for As contaminated groundwater treatment.

  10. A new phase diagram of water under negative pressure: The rise of the lowest-density clathrate s-III.

    Science.gov (United States)

    Huang, Yingying; Zhu, Chongqin; Wang, Lu; Cao, Xiaoxiao; Su, Yan; Jiang, Xue; Meng, Sheng; Zhao, Jijun; Zeng, Xiao Cheng

    2016-02-01

    Ice and ice clathrate are not only omnipresent across polar regions of Earth or under terrestrial oceans but also ubiquitous in the solar system such as on comets, asteroids, or icy moons of the giant planets. Depending on the surrounding environment (temperature and pressure), ice alone exhibits an exceptionally rich and complicated phase diagram with 17 known crystalline polymorphs. Water molecules also form clathrate compounds with inclusion of guest molecules, such as cubic structure I (s-I), cubic structure II (s-II), hexagonal structure H (s-H), tetragonal structure T (s-T), and tetragonal structure K (s-K). Recently, guest-free clathrate structure II (s-II), also known as ice XVI located in the negative-pressure region of the phase diagram of water, is synthesized in the laboratory and motivates scientists to reexamine other ice clathrates with low density. Using extensive Monte Carlo packing algorithm and dispersion-corrected density functional theory optimization, we predict a crystalline clathrate of cubic structure III (s-III) composed of two large icosihexahedral cavities (8(6)6(8)4(12)) and six small decahedral cavities (8(2)4(8)) per unit cell, which is dynamically stable by itself and can be fully stabilized by encapsulating an appropriate guest molecule in the large cavity. A new phase diagram of water ice with TIP4P/2005 (four-point transferable intermolecular potential/2005) model potential is constructed by considering a variety of candidate phases. The guest-free s-III clathrate with ultralow density overtakes s-II and s-H phases and emerges as the most stable ice polymorph in the pressure region below -5834 bar at 0 K and below -3411 bar at 300 K.

  11. How to improve the clinical development paradigm and its division into phases I, II and III.

    Science.gov (United States)

    Bamberger, Marion; Moore, Nicholas; Lechat, Philippe

    2011-01-01

    of improvement of the medical benefit (ASMR) [level II/III or IV/V]. Such requests mainly concern uncertainties regarding the transposability, the patient profile or correct usage in real life. Among the studies whose results were provided, in 15 cases the results were in line with expectations, in 6 cases they resulted in downward re-evaluations and the final 3 cases were inconclusive. The final recommendations of the round table were: Defining the medical need that is not covered by working in consultation (Industry and Health Authorities); Providing a Complementary Investigations Plan (PIC) after the MA at a very early stage to reinforce the early MA, and/or HTA (health technology assessment) preparation and monitoring (possible constraining actions); Enhanced use of modelling techniques and their transposability; "Intussusception" of phases to optimise the development of a complete dossier; Early "scientific opinions" (EMA, French Health Products Safety Agency [Afssaps], French Health Authority [HAS]); Raising the awareness of the authorities, industry, doctors and patients with regard to controlled observational studies; Developing the use of public data bases.

  12. Human duodenal phase III migrating motor complex activity is predominantly antegrade, as revealed by high-resolution manometry and colour pressure plots.

    Science.gov (United States)

    Andrews, J M; O'donovan, D G; Hebbard, G S; Malbert, C H; Doran, S M; Dent, J

    2002-08-01

    Abstract Late phase III migrating motor complex activity has been said to be primarily retroperistaltic but has not been assessed with high resolution manometry or three-dimensional colour pressure plots (pressure/time/distance). Duodenal phase III was examined in healthy young volunteers (seven male, two female) with a 20-lumen assembly. With the most proximal sidehole in the distal antrum, after a 4.5-cm interval 18 sideholes at 1.5-cm intervals spanned the duodenum with a final sidehole 3 cm beyond. Fasting pressures were recorded until phase III occurred. Comparisons were made between proximal (P) and distal (D) duodenum during early (E) (first 0.5-1 min) and late (L) (last 0.5-1 min) phase III. With colour pressure analysis, 121 of 180 pressure wave (PW) sequences were purely antegrade, two purely retrograde and 57 bidirectional. Ten of fifty-seven bidirectional PW sequences were complex, branching to become two separate sequences. Bidirectional sequences occurred more frequently in late than early phase III (L 43 vs. E 14 of 57), but their occurrence did not differ between proximal and distal duodenum (P31 vs. D 24 of 57). Antegrade propagation velocity was faster in late compared with early phase III (L 28.50 vs. E 17.05 mm s(-1); P = 0.006), but did not differ between proximal and distal duodenum. Colour pressure analysis also indicated an intermittent segmental pattern to phase III, with each subject exhibiting a change in velocity or direction, or a relative failure of peristalsis somewhere along the duodenum during part of phase III. Duodenal phase III is not homogenous and, in contrast with previous studies, does not primarily constitute a retroperistaltic pump. Colour pressure analysis is useful in interpreting intraluminal pressure profiles and may improve the sensitivity and specificity of clinical studies.

  13. 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.

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

    Science.gov (United States)

    2016-11-30

    Hurler Syndrome (MPS I); Hurler-Scheie Syndrome With Early Neurologic Involvement and/or Sensitization to Enzyme Replacement Therapy (ERT); 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. Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group

    Science.gov (United States)

    AOKI, Tomokazu; ARAKAWA, Yoshiki; UEBA, Tetsuya; ODA, Masashi; NISHIDA, Namiko; AKIYAMA, Yukinori; TSUKAHARA, Tetsuya; IWASAKI, Koichi; MIKUNI, Nobuhiro; MIYAMOTO, Susumu

    2017-01-01

    The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m2/day) (Day 1–5) plus various doses of ACNU (30, 35, 40, 45 mg/m2/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70–100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m2) plus ACNU (40 mg/m2). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12–35%) and 8% (95% CI, 4–15%). Median PFS was 13 months (95% CI, 9.2–17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67–89%) and 49% (95% CI, 33–57%). Median OS was 11.8 months (95% CI, 8.2–14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS. PMID:27725524

  16. A Phase I/II Study Combining Erlotinib and Dasatinib for Non-Small Cell Lung Cancer

    Science.gov (United States)

    Gold, Kathryn A.; Lee, J. Jack; Harun, Nusrat; Tang, Ximing; Price, Justina; Kawedia, Jitesh D.; Tran, Hai T.; Erasmus, Jeremy J.; Blumenschein, George R.; William, William N.; Wistuba, Ignacio I.

    2014-01-01

    Background. EGFR and Src are frequently activated in non-small cell lung cancer (NSCLC). In preclinical models, combining EGFR and Src inhibition has additive synergistic effects. We conducted a phase I/II trial of the combination of Src inhibitor dasatinib with EGFR inhibitor erlotinib to determine the maximum tolerated dose (MTD), pharmacokinetic drug interactions, biomarkers, and efficacy in NSCLC. Methods. The phase I 3+3 dose-escalation study enrolled patients with solid tumors to determine the MTD. The phase II trial enrolled patients with advanced NSCLC who had undergone no previous treatments to determine progression-free survival (PFS) and response. Pharmacokinetic and tissue biomarker analyses were performed. Results. MTD was 150 mg of erlotinib and 70 mg of dasatinib daily based on 12 patients treated in the phase I portion. No responses were observed in phase I. The 35 NSCLC patients treated in phase II had an overall disease control rate of 59% at 6 weeks. Five patients (15%) had partial responses; all had activating EGFR mutations. Median PFS was 3.3 months. Epithelial-mesenchymal transition markers did not correlate with outcomes. Conclusion. The combination of erlotinib and dasatinib is safe and feasible in NSCLC. The results of this study do not support use of this combination in molecularly unselected NSCLC. PMID:25170013

  17. NCI will no longer support investigator-initiated phase III clinical trials through R01 and P01s grants | Division of Cancer Prevention

    Science.gov (United States)

    The NCI has traditionally provided support for all phases of clinical trials and interventions via grants and cooperative agreements (including the R03, R21, R01, P01, U01, U10, and UM1 mechanisms). Historically, the majority of early phase trials have been conducted under R03, R21, R01, P01, U01, and UM1 activity codes, whereas most Phase III clinical trials have been conducted under the U10 activity code, with a limited number of Phase III clinical trials performed under the R01, P01, and U01 activity codes... |

  18. 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.

  19. Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

    DEFF Research Database (Denmark)

    Buch-Hansen, Trine Zeeberg; Bentzen, Lise Nørgaard; Hansen, Steinbjoern

    2010-01-01

    PURPOSE: We assessed the efficacy and toxicity of a fixed dose of docetaxel and prednisone, combined with escalating doses of gemcitabine (DGP). The primary endpoint was PSA response. METHODS: Fifteen patients were enrolled in the phase I and 50 patients entered the phase II. Patients were given ...

  20. Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

    DEFF Research Database (Denmark)

    Buch-Hansen, Trine Zeeberg; Bentzen, Lise Nørgaard; Hansen, Steinbjoern;

    2010-01-01

    PURPOSE: We assessed the efficacy and toxicity of a fixed dose of docetaxel and prednisone, combined with escalating doses of gemcitabine (DGP). The primary endpoint was PSA response. METHODS: Fifteen patients were enrolled in the phase I and 50 patients entered the phase II. Patients were given...

  1. Determination of submicrogram-per-liter concentrations of caffeine in surface water and groundwater samples by solid-phase extraction and liquid chromatography

    Science.gov (United States)

    Burkhardt, M.R.; Soliven, P.P.; Werner, S.L.; Vaught, D.G.

    1999-01-01

    A method for determining submicrogram-per-liter concentrations of caffeine in surface water and groundwater samples has been developed. Caffeine is extracted from a 1 L water sample with a 0.5 g graphitized carbon-based solid-phase cartridge, eluted with methylene chloride-methanol (80 + 20, v/v), and analyzed by liquid chromatography with photodiode-array detection. The single-operator method detection limit for organic-free water samples was 0.02 ??g/L. Mean recoveries and relative standard deviations were 93 ?? 13% for organicfree water samples fortified at 0.04 ??g/L and 84 ?? 4% for laboratory reagent spikes fortified at 0.5 ??g/L. Environmental concentrations of caffeine ranged from 0.003 to 1.44 ??g/L in surface water samples and from 0.01 to 0.08 ??g/L in groundwater samples.

  2. Speciation of Cr(III) and Cr(VI) after column solid phase extraction on Amberlite XAD-2010.

    Science.gov (United States)

    Bulut, V N; Duran, C; Tufekci, M; Elci, L; Soylak, M

    2007-05-08

    A speciation procedure for Cr(III) and Cr(VI) based on column solid phase extraction on Amberlite XAD-2010 and flame atomic absorption spectrometry combination. Cr(VI) was quantitatively recovered on Amberlite XAD-2010 resin at pH range of 2.0-3.0 as its diethyldithiocarbamate complex, while the recoveries of Cr(III) was below 5%. The influences of the various parameters including amounts of the reagents, eluent type and its volume, sample volume, etc., on the quantitative recoveries were examined. The interference of matrix and coexistent elements for method were studied. The detection limit (corresponding to three times the standard deviation of the blank) and the enrichment factor for Cr(VI) were found to be 1.28 microg/L and 25, respectively. To verify the accuracy of the method, drinking water certified reference material (CRM-TMDW-500) was analyzed and the results obtained were in good agreement with the certified value. The proposed method has been successfully applied to the speciation of Cr(III) and Cr(VI) in water samples and preconcentration of total chromium in environmental samples.

  3. Temperature and energy deficit in the ground during operation and recovery phases of closed-loop ground source heat pump system: Effect of the groundwater flow

    Science.gov (United States)

    Erol, Selcuk; Francois, Bertrand

    2016-04-01

    The advection/dispersion mechanism of the groundwater flow in the ground has a significant effect on a borehole heat exchanger (BHE) to enhance its thermal performance. However, the amount of energy extracted from the ground never disappears and only shifts with the magnitude of the effective thermal velocity in the infinite domain. In this work, we focus on the temperature and the energy balance of the ground in an advection/dispersion dominated heat transfer system during the operation period of a BHE and the subsequent recovery phase when the system is idle. The problem is treated with single BHE and multi-BHEs systems, for different representative geology and different groundwater flow velocity. In order to assess the thermal energy deficit due to heat extraction from the ground, we used the finite line source analytical model, developed recently (Erol et al., 2015) that provides the temperature distributions around the boreholes for discontinuous heat extraction. The model is developed based on the Green's function, which is the solution of heat conduction/advection/dispersion equation in porous media, for discontinuous heat extraction by analytically convoluting rectangular function or pulses in time domain. The results demonstrate the significant positive impact of the groundwater flow for the recovery in terms of temperature deficit at the location of the borehole. However, the total thermal energy deficit is not affected by the groundwater movement. The energy balance of the ground is the same no matter the prevailing heat transfer system, which can be only conduction or advection/dispersion. In addition, the energy balance of the ground is not based on either the duration of the production period operation or of the recovery phase, but depends on the total amount of heat that is extracted and on the bulk volumetric heat capacity of the ground.

  4. Induction chemotherapy before chemoradiotherapy and surgery for locally advanced rectal cancer. Is it time for a randomized phase III trial?

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, Claus [Frankfurt Univ. (Germany). Klinik fuer Strahlentherapie und Onkologie; Arnold, Dirk [Halle Univ. (Germany). Klinik und Poliklinik fuer Innere Medizin IV; Becker, Heinz; Ghadimi, Michael; Liersch, Torsten [Goettingen Univ. (Germany). Klinik fuer Allgemein- und Visceralchirurgie; Fietkau, Rainer; Sauer, Rolf [Erlangen Univ. (Germany). Strahlenklinik; Graeven, Ullrich [Kliniken Maria Hilf GmbH, Moenchengladbach (Germany). Klinik fuer Haematologie, Onkologie und Gastroenterologie; Hess, Clemens [Goettingen Univ. (Germany). Klinik fuer Strahlentherapie und Radioonkologie; Hofheinz, Ralf [Universitaetsmedizin Mannheim (Germany). III. Medizinische Klinik Haematologie und Internistische Onkologie; Hohenberger, Werner [Erlangen Univ. (Germany). Chirurgische Klinik; Post, Stefan [Universitaetsmedizin Mannheim (Germany). Chirurgische Klinik; Raab, Rudolf [Klinikum Oldenburg (Germany). Klinik fuer Allgemein- und Visceralchirurgie; Wenz, Frederick [Universitaetsmedizin Mannheim (Germany). Klinik fuer Strahlentherapie und Radioonkologie

    2010-12-15

    Background: In the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of distant metastases is the predominant mode of failure in rectal cancer patients today. Integrating more effective systemic therapy into combined modality programs is the challenge. The question that needs to be addressed is how and when to apply systemic treatment with adequate dose and intensity. Material and Methods: This review article focuses on phase II-III trials designed to improve 5-fluorouracil (5-FU)-based combined modality treatment for rectal cancer patients through the inclusion of concurrent, adjuvant or, most recently, induction combination chemotherapy. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. Results: After preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal, or investigator's discretion. In order to be able to apply chemotherapy with sufficient dose and intensity, an innovative approach is to deliver systemic therapy prior to preoperative CRT rather than adjuvant chemotherapy. Emerging evidence from several phase II trials and, recently, randomized phase II trials indicate that induction chemotherapy is feasible, does not compromise CRT or surgical resection, and enables the delivery of chemotherapy in adequate dose and intensity. Although this approach did not increase local efficacy in recent trials (e.g., pathological complete response rates, tumor regression, R0 resection rates, local control), it may help to improve control of distant disease. Conclusion: Whether this improvement in applicability and dose density of chemotherapy will ultimately translate into improved disease-free survival will have to be tested in a larger phase III trial. (orig.)

  5. Job Aid Manuals for Phase III-DEVELOP of the Instructional Systems Development Model

    Science.gov (United States)

    1980-05-01

    THE FIVE ISD PHASES IlaBLCK IN EACH PHASE ARE: 1.1 1.2 C1 STUC 1.4 1.5~SELECT COSRC ANALYZE SELECTPHASE g ATASKS/YZ EXISTING INSTRUCTIONAL] PHASEi U...tile pesir.wn 4 S. Inspet tile pges 46 6. Ispect Ile raft swgeinr 47 7. Isslew tile nifs 48 kM. IsmOr visth tll Coo dwcde IC0 21 Kytoiders or WvidpS 49

  6. Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial

    Directory of Open Access Journals (Sweden)

    Combs Stephanie E

    2012-04-01

    Full Text Available Abstract Background Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed. Carbon ions offer physical and biological advantages. 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 increase relative biological effectiveness (RBE, which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed. Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions. Methods and design In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study. Within the Phase I part, increasing doses from 12 × 3 Gy E to 18

  7. Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

    Directory of Open Access Journals (Sweden)

    Dollinger Matthias M

    2010-08-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12 were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS, time to progression (TTP, tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC formed part of the protocol. Results Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6] or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]. Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. Trial Registration Current Controlled Trials ISRCTN64487365.

  8. 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

  9. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma

    NARCIS (Netherlands)

    A.M.M. Eggermont (Alexander); S. Suciu (Stefan); A. Testori (Alessandro); M. Santinami (Mario); W.H.J. Kruit (Wim); J. Marsden; C.J.A. Punt (Cornelis); F. Salès (François); R. Dummer (Reinhard); C. Robert (Caroline); D. Schadendorf (Dirk); P. Patel (Poulam); G. de Schaetzen (Gaetan); A. Spatz (Alan); U. Keilholz (Ulrich)

    2012-01-01

    textabstractPurpose: Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. Patients and Methods: In all, 1,256 patients with resected stage III melanoma were randomly

  10. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Scagliotti, G.V.; Parikh, P.; Pawel, J. von

    2008-01-01

    Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study ...... neutropenia (P = .002); and alopecia (P

  11. Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose Escalation Study

    Directory of Open Access Journals (Sweden)

    D. Nathan W. Kim

    2014-11-01

    Full Text Available Introduction: Stereotactic body radiation therapy (SBRT is an area of active investigation for treatment of prostate cancer. In our phase I dose escalation study maximum tolerated dose was not reached, and subsequently phase II study has been completed. The purpose of this article is to review our experiences of dose escalated SBRT for localized prostate cancer. Methods and Materials: Patients enrolled to phase I/II study from 2006-2011 were reviewed. Prescription dose groups were 45, 47.5 and 50 Gray (Gy in 5 fractions over 2.5 weeks. Toxicity and quality of life questionnaire data were collected and analyzed. Descriptive statistics were obtained in the form of means, medians, and ranges for the continuous variables, and frequencies and percentages for the categoric variables. Results: 91 patients were enrolled from five institutions. Median follow up for PSA evaluation was 42 months. PSA control remains at 99%. While the maximum tolerated dose was not reached in the phase I study, excess high grade rectal toxicity (10.6% was noted in the phase II study. The 13 patients treated to 50 Gy in the phase I study that did not have high grade rectal toxicity, in retrospect met these parameters and have not had further events on longer follow up. Conclusion: PSA control rate, even for patients with intermediate risk, is thus far excellent at these dose levels. This study provides a platform for exploration of SBRT based clinical trials aimed at optimizing outcome for intermediate and high risk patients. High grade toxicities specifically related to the rectum were observed in a small but meaningful minority at the highest dose level. Dose constraints based on physiologic parameters have been defined to mitigate this risk, and strategies to minimize rectal exposure to such doses are being explored.

  12. CHEMKIN-III: A FORTRAN chemical kinetics package for the analysis of gas-phase chemical and plasma kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Kee, R.J.; Rupley, F.M.; Meeks, E.; Miller, J.A.

    1996-05-01

    This document is the user`s manual for the third-generation CHEMKIN package. CHEMKIN is a software package whose purpose is to facilitate the formation, solution, and interpretation of problems involving elementary gas-phase chemical kinetics. It provides a flexible and powerful tool for incorporating complex chemical kinetics into simulations of fluid dynamics. The package consists of two major software components: an Interpreter and a Gas-Phase Subroutine Library. The Interpreter is a program that reads a symbolic description of an elementary, user-specified chemical reaction mechanism. One output from the Interpreter is a data file that forms a link to the Gas-Phase Subroutine Library. This library is a collection of about 100 highly modular FORTRAN subroutines that may be called to return information on equations of state, thermodynamic properties, and chemical production rates. CHEMKIN-III includes capabilities for treating multi-fluid plasma systems, that are not in thermal equilibrium. These new capabilities allow researchers to describe chemistry systems that are characterized by more than one temperature, in which reactions may depend on temperatures associated with different species; i.e. reactions may be driven by collisions with electrons, ions, or charge-neutral species. These new features have been implemented in such a way as to require little or no changes to CHEMKIN implementation for systems in thermal equilibrium, where all species share the same gas temperature. CHEMKIN-III now has the capability to handle weakly ionized plasma chemistry, especially for application related to advanced semiconductor processing.

  13. A multicenter,phase III trial of hemocoagulase Agkistrodon:hemostasis,coagulation,and safety in patients undergoing abdominal surgery

    Institute of Scientific and Technical Information of China (English)

    WEI Jun-min; LI Jie; XU Jing-yong; ZHENG Qing-shan; ZHU Ming-wei; ZHANG Zhong-tao; JIA Zhen-geng; HE Xiao-dong; WAN Yuan-lian; WANG Shan; XIU Dian-rong; TANG Yun

    2010-01-01

    Background Hemocoagulase Agkistrodon for injection is a single component thrombin which has passed phases I and II clinical trials. The purpose of this phase III clinical trial was to evaluate the effect of Hemocoagulase Agkistrodon on hemostasis and coagulation in abdominal skin and subcutaneous incisions and to assess the safety of this agent in surgical patients. Methods This is a phase III, prospective, randomized, double-blind, and controlled multicenter clinical trial including 432 consecutive patients randomized into either a study group (injected with hemocoagulase Agkistrodon at 2 U, n=324) or a control group (injected with hemocoagulase Atrox, n=108). The hemostatic time, hemorrhagic volume, hemorrhagic volume per unit area, blood coagulation, and adverse events were measured and compared between the two groups. Results The mean hemostatic time in the study group was (36.8±18.7) seconds; the hemorrhagic volume was (3.77±3.93) g; and the hemorrhagic volume per unit area was (0.091±0.125) g/cm~2. In the control group, the corresponding values were (38.1±19.7) seconds, (4.00±4.75) g, and (0.095±0.101) g/cm~2, respectively. No significant difference in values existed between the two groups (P >0.05). Blood coagulation results and hepatic and renal function were also similar between the two groups. Adverse events were reported in two cases, but were deemed non-drug-related. Conclusions Hemocoagulase Agkistrodon has good hemostatic and coagulative function and is safe for the use of arresting capillary hemorrhage that occurs while incising the abdomen during surgery.

  14. Microbial Reduction of Al-Substituted Fe(III) (Hydr)oxides: Redefining the Reducing Capacity of Fe Phases in Natural Soils

    Science.gov (United States)

    Ekstrom, E. B.; Hansel, C. M.

    2008-12-01

    Aluminum, one of the most abundant elements in soils and sediments, is also commonly found co- precipitated with Fe in natural Fe (III) (hydr)oxides. Although significant progress has been made elucidating the rates and solid-phase products of Fe(III) reduction by dissimilatory iron-reducing bacteria (DIRB) grown on pure, synthetic iron (hydr)oxides, relatively little is known about the impact of Al co-precipitation within Fe(III) (hydr)oxides on growth and bacterial Fe reduction by DIRB. Two previous studies investigating bacterial Fe reduction of Al-containing goethite minerals found contrasting results. To better understand the role of Al-substitution in controlling the rate, extent, and products of bacterial Fe(III) reduction, we have performed Fe(III) reduction experiments with the model DIRB, Shewanella putrefaciens CN32 grown on synthetic ferrihydrite, lepidocrocite, and goethite containing between 0 and 13 mole % Al. These experiments reveal that the impact of Al varies among Fe(III) (hydr)oxide minerals. Increasing Al-substitution in ferrihydrite results in a decrease of bacterial growth and Fe(III) reduction, while increasing Al content within lepidocrocite causes increased bacterial growth and Fe(III) reduction. For goethite, no change in Fe(III) reduction or growth is observed when growth on goethite containing increasing Al-substitution. Given the prevalence of Al-substitution in natural Fe(III) (hydr)oxides, our results bring into question the conventional assumptions about Fe(III) oxide bioavailability and suggest a more prominent role of natural lepidocrocite phases in impacting DIRB activity in soils and sediments.

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

    Energy Technology Data Exchange (ETDEWEB)

    None

    1998-07-01

    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 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 HITAF Combustor; Task 2.2 HITAF Air Heaters; Task 6 HIPPS Commercial Plant Design Update.

  16. 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.

  17. Evaluated kinetic and photochemical data for atmospheric chemistry: Volume III ? gas phase reactions of inorganic halogens

    OpenAIRE

    Atkinson, R.; Baulch, D. L.; Cox, R A; J. N. Crowley; Hampson, R. F.; Hynes, R. G.; Jenkin, M. E.; M. J. Rossi; Troe, J.

    2007-01-01

    International audience; This article, the third in the series, presents kinetic and photochemical data evaluated by the IUPAC Subcommittee on Gas Kinetic Data Evaluation for Atmospheric Chemistry. It covers the gas phase and photochemical reactions of inorganic halogen species, which were last published in J. Phys. Chem. Ref. Data, in 2000 (Atkinson et al., 2000), were updated on the IUPAC website in 2003 and are updated again in the present evaluation. The article consists of a summary sheet...

  18. Laser Induced Chemical Vapor Phase Epitaxial Growth of III-V semiconductor Films

    Science.gov (United States)

    1991-05-14

    temperatures for the preparation and crystal growth of semiconductors . During the first phase of this program at Southern Methodist University, the epitaxial...approach to the preparation of device-quality 4 semiconductor films of controlled electrical and stru -.tural propierties . The excitation of reaction...temperatures for the preparation and crystal growth of semiconductors . The vapors of essentially all metalorganic compounds and group V hydrides are colorless

  19. Phase Coupling Between Spectral Components of Collapsing Langmuir Solitons in Solar Type III Radio Bursts

    Science.gov (United States)

    Thejappa, G.; MacDowall, R. J.; Bergamo, M.

    2012-01-01

    We present the high time resolution observations of one of the Langmuir wave packets obtained in the source region of a solar type III radio burst. This wave packet satisfies the threshold condition of the supersonic modulational instability, as well as the criterion of a collapsing Langmuir soliton, i.e., the spatial scale derived from its peak intensity is less than that derived from its short time scale. The spectrum of t his wave packet contains an intense spectral peak at local electron plasma frequency, f(sub pe) and relatively weaker peaks at 2f(sub pe) and 3f(sub pe). We apply the wavelet based bispectral analysis technique on this wave packet and compute the bicoherence between its spectral components. It is found that the bicoherence exhibits two peaks at (approximately f(sub pe), approximately f(sub pe)) and (approximately f(sub pe) approximately 2f(sub pe)), which strongly suggest that the spectral peak at 2f(sub pe) probably corresponds to the second harmonic radio emission, generated as a result of the merging of antiparallel propagating Langmuir waves trapped in the collapsing Langmuir soliton, and, the spectral peak at 3f(sub pe) probably corresponds to the third harmonic radio emission, generated as a result of merging of a trapped Langmuir wave and a second harmonic electromagnetic wave.

  20. Rheumatic disease in a Philippine village. II: a WHO-ILAR-APLAR COPCORD study, phases II and III.

    Science.gov (United States)

    Wigley, R; Manahan, L; Muirden, K D; Caragay, R; Pinfold, B; Couchman, K G; Valkenburg, H A

    1991-01-01

    Many difficulties were encountered in a population survey of rheumatic complaints in a remote village area in the Philippines affecting the reliability of estimates of population prevalence. In phase I, a simple questionnaire identified 269 adults out of 950 who had rheumatic symptoms. In Phase II, 234 or 87% of positive respondents were requestioned using a more detailed pro forma. There were 196 with peripheral joint pain, 67 with neck pain and 137 with back pain. One third attributed their symptoms to work and 127 subjects had to stop work because of their complaints. Disability, including an inability to carry loads, affected nearly 1.8% of the population. Questions designed to detect rheumatoid arthritis and gout were not satisfactorily answered. Of those with complaints, 82% indicated that they still required help for their symptoms. In phase III, 166 subjects were medically examined. Osteoarthritis of the knee was found in 25 and 17 had Heberden's nodes. There were 16 with epicondylitis; 16 had rotator cuff pain and 35 had levator scapulae insertion pain. Three of these and three others had neck or shoulder swellings related to carrying loads on poles. Definite rheumatoid arthritis was diagnosed in two subjects and gout in five. No case of ankylosing spondylitis was identified. Thus, rheumatic complaints were common in this rural community and were frequently severe enough to cause disability and loss of time from work. Health worker education is required on how to handle these problems.

  1. A phase I/II trial of Erlotinib in higher risk myelodysplastic syndromes and acute myeloid leukemia after azacitidine failure.

    Science.gov (United States)

    Thepot, Sylvain; Boehrer, Simone; Seegers, Valérie; Prebet, Thomas; Beyne-Rauzy, Odile; Wattel, Eric; Delaunay, Jacques; Raffoux, Emmanuel; Hunault, Mathilde; Jourdan, Eric; Chermat, Fatiha; Sebert, Marie; Kroemer, Guido; Fenaux, Pierre; Adès, Lionel

    2014-12-01

    Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100mg/day (n=5) or 150mg/day (n=25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated. This outpatient treatment was well tolerated with limited grade III-IV extra hematological toxicities (skin (n=1), and diarrhea (n=3). Response was observed in 6 patients (20%) including 1 complete remission (CR), 1 marrow CR and 4 hematological improvement (2 erythroid and 2 on platelets). Median duration of response was 5 months. Erlotinib appears to induce a significant number of responses in higher risk MDS/AML having failed AZA treatment. Given the good safety profile of Erlotinib, its combination with other drugs could be tested in the future in MDS and AML.

  2. 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

    2007-04-01

    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 classroom observations recorded communications between the children and their teachers. These occurred: 6 weeks before teaching; during the week immediately prior to teaching; during the week immediately following teaching. For the control group, two 2-h observations were separated by a 5-week interval without PECS teaching. Communicative initiations and dyadic interactions increased significantly between the children and teachers in the PECS group but not for the control group.

  3. Idaho Water Rental Pilot Project probability/coordination study resident fish and wildlife impacts, Phase III. Annual report

    Energy Technology Data Exchange (ETDEWEB)

    Leitzinger, E.

    1996-09-01

    Phase III began in 1995 with the overall goal of quantifying changes in resident fish habitat in the Snake River basin upstream of Brownlee Reservoir resulting from the release of salmon flow augmentation water. Existing data, in the form of weighted usable area versus flow relationships, were used to estimate habitat changes for white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss)in the Snake River between C.J. Strike Dam and Brownlee pool. The increased flows resulted in increased white sturgeon habitat for most life stages. Rainbow trout adult and spawning habitat increased while juvenile and fry habitat generally decreased. Whether or not these short term increases in habitat result in long term benefits to the fish populations has yet to be determined.

  4. Idaho Water Rental Pilot Project Probability/Coordination Study Resident Fish and Wildlife Impact Phase III, 1995 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Leitzinger, Eric J. (Idaho Department of Fish and Game, Boise, ID)

    1996-09-01

    Phase III began in 1995 with the overall goal of quantifying changes in resident fish habitat in the Snake River basin upstream of Brownlee Reservoir resulting from the release of salmon flow augmentation water. Existing data, in the form of weighted usable area versus flow relationships, were used to estimate habitat changes for white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) in the Snake River between C.J. Strike Dam and Brownlee pool. The increased flows resulted in increased white sturgeon habitat for most life stages. Rainbow trout adult and spawning habitat increased while juvenile and fry habitat generally decreased. Whether or not these short term increases in habitat result in long term benefits to the fish populations has yet to be determined.

  5. Adoption of community-based cardiac rehabilitation programs and physical activity following phase III cardiac rehabilitation in Scotland: a prospective and predictive study.

    Science.gov (United States)

    Sniehotta, Falko F; Gorski, Charlotta; Araujo-Soares, Vera

    2010-09-01

    Little is known about levels of physical activity and attendance at phase IV community-based Cardiac Rehabilitation (CR) programs following completion of exercise-focussed, hospital-based phase III CR. This study aims to test, compare and combine the predictive utility of the Common-Sense Self-Regulation Model (CS-SRM) and the extended Theory of Planned Behaviour (TPB) with action planning for two rehabilitation behaviours: physical activity and phase IV CR attendance. Individuals diagnosed with coronary heart disease (n = 103) completed baseline measures of illness perceptions, intentions, perceived behavioural control (PBC), action planning and past physical activity in the last week of a phase III CR program, and 95 participants completed follow-up measures of physical activity and attended phase IV CR (objectively confirmed) 2 months later. Only one predictor (PBC/cyclical timeline) significantly predicted levels and change of physical activity. While illness perceptions were not predictive of phase IV CR attendance, the extended TPB model showed good predictive power with action planning and intention as the most powerful predictors. Amongst participants who planned when and where to attend phase IV CR at the end of phase III rehabilitation, 65.9% subsequently attended a phase IV CR program compared to only 18.5% of those who had not made a plan. This study adds to our understanding of cardiac rehabilitation behaviour after completion of health service delivered programs. Comparing theoretical models and rehabilitation behaviours contributes to the development of behaviour theory.

  6. Open versus laparoscopically-assisted oesophagectomy for cancer: a multicentre randomised controlled phase III trial - the MIRO trial

    Directory of Open Access Journals (Sweden)

    Msika Simon

    2011-07-01

    Full Text Available Abstract Background Open transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to 50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma. Methods/Design The MIRO trial is an open, controlled, prospective, randomised multicentre phase III trial. Patients in study arm A will receive laparoscopic-assisted oesophagectomy, i.e., a transthoracic oesophagectomy with two-field lymphadenectomy and laparoscopic gastric mobilisation. Patients in study arm B will receive the same procedure, but with the conventional open abdominal approach. The primary objective of the study is to evaluate the major postoperative 30-day morbidity. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, 30-day pulmonary morbidity, disease-free survival, overall survival as well as quality of life and to perform medico-economic analysis. A total of 200 patients will be enrolled, and two safety analyses will be performed using 25 and 50 patients included in arm A. Discussion Postoperative morbidity remains high after oesophageal cancer surgery, especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths. This study represents the first randomised controlled phase III trial to evaluate the benefits of the minimally invasive approach with respect to the postoperative course and oncological outcomes in oesophageal cancer surgery. Trial Registration NCT00937456 (ClinicalTrials.gov

  7. From research to phase III: preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccine.

    Science.gov (United States)

    Guy, Bruno; Barrere, Beatrice; Malinowski, Claire; Saville, Melanie; Teyssou, Remy; Lang, Jean

    2011-09-23

    Dengue vaccine development has reached a major milestone with the initiation, in 2010, of the first phase III clinical trial to investigate the Sanofi Pasteur CYD tetravalent dengue vaccine (TDV). The CYD TDV candidate is composed of four recombinant, live, attenuated vaccines (CYD-1-4) based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the pre-membrane and envelope genes of one of the four dengue virus serotypes. The vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D, and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies showed that CYD TDV induces controlled stimulation of human dendritic cells, and significant immune responses in monkeys. Scale up and industrialization are being conducted in parallel with preclinical and clinical development to fulfill the needs of phase II/III trials, and to anticipate and facilitate supply and access to vaccine in the countries where the dengue disease burden makes it an urgent public health priority. The vaccine has now been administered to more than 6000 children and adults from dengue endemic and non-endemic areas and no safety concerns have arisen in any of the completed or ongoing trials. A three-dose vaccination regimen induces an immune response against all four serotypes in the large majority of vaccinees. Preexisting flavivirus immunity favors quicker and higher immune responses to CYD TDV, without adversely effecting clinical safety or increasing vaccine viremia. The observed level and nature of the cellular immune responses in humans are consistent with the good safety and immunogenicity profile of the vaccine. Preliminary results of an ongoing, proof-of-concept efficacy and large scale safety study in Thai children are expected by the end of 2012. Here we discuss the different steps and challenges of developing CYD TDV, from research to industrialization, and summarize some of the challenges to the successful

  8. Intercalation-induced phases in layer compounds of the A /SUP III/ B /SUP VI/ -type

    Energy Technology Data Exchange (ETDEWEB)

    Kovalyuk, Z.D.; Pyrlya, M.N.; Seredyuk, A.I.; Tovstyuk, K.D.

    1986-03-01

    The authors investigate the kinetics of combined electrochemical intercalation and the physicochemical properties of the introduced phases. InSe and GaSe single crystals were used in the experiments; the crystals were grown by the Bridgman method. The authors determined the concentration dependences of the electrode potentials and electrical conductivity of the compounds InSe and GaSe intercalated with lithium and lead. The results of the measurements are presented. Lithium and lead enter into the matrix of the crystals in a nonconducting state.

  9. Chelating agent free solid phase extraction (CAF-SPE) method for separation and/or preconcentration of iron(III) ions

    OpenAIRE

    for, Chelating agent free solid phase extract

    2014-01-01

    This paper presents a chelating agent free solid phase extraction (CAF-SPE) method for the separation and/or preconcentration of trace iron(III) ions. This method is based on the sorption of Fe(III) ions without using any chelating agent onto Amberlyst 36 resin. A good relative standard deviation (3%), high recovery (>95%), high enrichment factor (100), and low detection limit (0.32 m g L-1) were obtained. The adsorption capacity of resin was 117 mg g-1 for iron(III). The me...

  10. Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials.

    Science.gov (United States)

    Alberts, David S; Muggia, Franco M; Carmichael, James; Winer, Eric P; Jahanzeb, Mohammad; Venook, Alan P; Skubitz, Keith M; Rivera, Edgardo; Sparano, Joseph A; DiBella, Nicholas J; Stewart, Simon J; Kavanagh, John J; Gabizon, Alberto A

    2004-12-01

    Preclinical studies have established the pharmacologic advantages of liposomal anthracyclines, including pharmacokinetic profiles after bolus dosing that resemble continuous infusion of conventional anthracyclines, increased drug concentrations in tumor cells compared with the surrounding tissues, and reduced toxicity relative to conventional anthracycline treatment. Based on these studies, many phase I and phase II clinical trials were conducted to assess the safety and potential activity of liposomal anthracyclines in the management of both solid and hematologic tumors. These studies provided valuable insight into the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome [DNX]) over a range of doses, either as single-agent therapy or in combination with other cytotoxic agents. Other liposomal anthracyclines in development may be well tolerated but their activity remains to be elucidated by clinical trials. The available data also suggest that liposomal anthracyclines have activity not only against tumor types with known sensitivity to conventional anthracyclines, but also potentially for tumors that are typically anthracycline-resistant. Despite the availability of clinical data from a wide variety of tumor types and patient populations, further studies of liposomal anthracycline therapy are needed to fully establish their safety, efficacy, and dosing in the treatment of these patients.

  11. DNA display III. Solid-phase organic synthesis on unprotected DNA.

    Directory of Open Access Journals (Sweden)

    David R Halpin

    2004-07-01

    Full Text Available DNA-directed synthesis represents a powerful new tool for molecular discovery. Its ultimate utility, however, hinges upon the diversity of chemical reactions that can be executed in the presence of unprotected DNA. We present a solid-phase reaction format that makes possible the use of standard organic reaction conditions and common reagents to facilitate chemical transformations on unprotected DNA supports. We demonstrate the feasibility of this strategy by comprehensively adapting solid-phase 9-fluorenylmethyoxycarbonyl-based peptide synthesis to be DNA-compatible, and we describe a set of tools for the adaptation of other chemistries. Efficient peptide coupling to DNA was observed for all 33 amino acids tested, and polypeptides as long as 12 amino acids were synthesized on DNA supports. Beyond the direct implications for synthesis of peptide-DNA conjugates, the methods described offer a general strategy for organic synthesis on unprotected DNA. Their employment can facilitate the generation of chemically diverse DNA-encoded molecular populations amenable to in vitro evolution and genetic manipulation.

  12. A phase I-II trial of fludarabine, bendamustine and rituximab (FBR) in previously treated patients with CLL.

    Science.gov (United States)

    Jain, Nitin; Balakrishnan, Kumudha; Ferrajoli, Alessandra; O'Brien, Susan M; Burger, Jan A; Kadia, Tapan M; Cortes, Jorge E; Ayres, Mary L; Tambaro, Francesco Paolo; Keating, Michael J; Gandhi, Varsha; Wierda, William G

    2016-09-15

    Chemoimmunotherapy regimens have been the standard first-line therapy for patients with chronic lymphocytic leukemia (CLL). For young, fit patients the standard of care is combination of fludarabine, cyclophosphamide, and rituximab (FCR). Based on the preclinical work demonstrating that bendamustine combined with fludarabine resulted in increased DNA damage, we designed a phase I-II clinical trial with fludarabine, bendamustine, and rituximab (FBR) for patients with relapsed/refractory CLL. Treatment consisted of fludarabine 20 mg/m2 daily x 3 days and rituximab 375-500 mg/m2 x 1 day. Phase I included bendamustine at increasing doses of 20, 30, 40, or 50 mg/m2 daily x 3 days; phase II was with FR, and B at the selected dose. DNA damage response (H2AX phosphorylation) was evaluated in a subset of patients. Fifty-one patients were enrolled. The median age was 62 years; median number of prior therapies was 2; 40% had del(11q); and 41 patients had received prior FCR-based therapies. Hematologic toxicity was more common in ≥40 mg/m2 dose cohorts. Maximum tolerated dose (MTD) was not identified. Bendamustine-elicited H2AX phosphorylation was not dose-dependent, but markedly increased after fludarabine. We identified bendamustine 30 mg/m2 as the safe dose for phase II. The overall response rate (ORR) was 67% with 36% complete response (CR) / CR with incomplete count recovery (CRi). Younger patients (<65 years) had significantly higher ORR (81% vs. 50%; p=0.038). The median progression-free survival was 19 months, and the median overall survival was 52.5 months. FBR is an effective and tolerable CIT regimen for patients with relapsed CLL.

  13. Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials

    Science.gov (United States)

    Doblinger, Jakob; Cometti, Barbara; Trevisan, Silvia; Griesinger, Georg

    2016-01-01

    Objective To summarize efficacy and safety data on a new progesterone compound which is available for subcutaneous administration as compared to vaginally administered progesterone for luteal phase support in patients undergoing IVF treatment. Design Data from two randomized phase III trials (07EU/Prg06 and 07USA/Prg05) performed according to GCP standards with a total sample size of 1435 per-protocol patients were meta-analyzed on an individual patient data level. Setting University affiliated reproductive medicine unit. Patients Subcutaneous progesterone was administered to a total of 714 subjects and vaginal progesterone was administered to a total of 721 subjects who underwent fresh embryo transfer after ovarian stimulation followed by IVF or ICSI. The subjects were between 18 and 42 years old and had a BMI <30kg/m2. Interventions Subcutaneous progesterone 25 mg daily vs. either progesterone vaginal gel 90 mg daily (07EU/Prg06) or 100 mg intravaginal twice a day (07USA/Prg05) for luteal phase support in IVF patients. Main outcome measures Ongoing pregnancy rate beyond 10 gestational weeks, live birth rate and OHSS risk. Results The administration of subcutaneous progesterone versus intra-vaginal progesterone had no impact on ongoing pregnancy likelihood (OR = 0.865, 95% CI 0.694 to 1.077; P = n.s.), live birth likelihood (OR = 0.889, 95% CI 0.714 to 1.106; P = n.s.) or OHSS risk (OR = 0.995, 95% CI 0.565 to 1.754; P = n.s.) in regression analyses accounting for clustering of patients within trials, while adjusting for important confounders. Only female age and number of oocytes retrieved were significant predictors of live birth likelihood and OHSS risk. Conclusion No statistical significant or clinical significant differences exist between subcutaneous and vaginal progesterone for luteal phase support. PMID:26991890

  14. Structural transition of PETN-I to ferroelastic orthorhombic phase PETN-III at elevated pressures.

    Science.gov (United States)

    Tschauner, O; Kiefer, B; Lee, Y; Pravica, M; Nicol, M; Kim, E

    2007-09-07

    Using powder x-ray diffraction and first-principles calculations, we provide evidence for a structural transition of PETN-I below 6 GPa to an orthorhombic phase of space group P2(1)2(1)2. The transition can be rationalized as shear-stress induced and ferroelastic, which involves a slight static displacement of the molecules that breaks the fourfold symmetry of PETN-I. Previously reported changes in the optical spectra reflect a lifting of the twofold degeneracy of modes in tetragonal PETN-I. The observed transition is expected to induce soft shear compliances along specific directions in PETN crystallites that may relate to the observed dependence of detonation pressure on crystal orientation.

  15. 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.......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....

  16. Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years, the Nordic Lymphoma Group phase I+II trial NLG-MCL4

    DEFF Research Database (Denmark)

    Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna;

    2016-01-01

    For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untr......For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years...

  17. Hollow fiber liquid phase microextraction combined with electrothermal atomic absorption spectrometry for the speciation of arsenic (III) and arsenic (V) in fresh waters and human hair extracts

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Hongmei [Department of Chemistry, Wuhan University, Wuhan 430072 (China); Hu Bin [Department of Chemistry, Wuhan University, Wuhan 430072 (China)], E-mail: binhu@whu.edu.cn; Chen Beibei; Xia Linbo [Department of Chemistry, Wuhan University, Wuhan 430072 (China)

    2009-02-16

    A new method of hollow fiber liquid phase microextraction (HF-LPME) using ammonium pyrrolidine dithiocarbamate (APDC) as extractant combined with electrothermal atomic absorption spectrometry (ETAAS) using Pd as permanent modifier has been described for the speciation of As(III) and As(V). In a pH range of 3.0-4.0, the complex of As(III)-APDC complex can be extracted using toluene as the extraction solvent leaving As(V) in the aqueous layer. The post extraction organic phase was directly injected into ETAAS for the determination of As(III). To determine total arsenic in the samples, first As(V) was reduced to As(III) by L-cysteine, and then a microextraction method was performed prior to the determination of total arsenic. As(V) assay was based on subtracting As(III) form the total arsenic. All parameters, such as pH of solution, type of organic solvent, the amount of APDC, stirring rate and extraction time, affecting the separation of As(III) from As(V) and the extraction efficiency of As(III) were investigated, and the optimized extraction conditions were established. Under optimized conditions, a detection limit of 0.12 ng mL{sup -1} with enrichment factor of 78 was achieved. The relative standard deviation (R.S.D.) of the method for five replicate determinations of 5 ng mL{sup -1} As(III) was 8%. The developed method was applied to the speciation of As(III) and As(V) in fresh water and human hair extracts, and the recoveries for the spiked samples are 86-109%. In order to validate the developed method, three certified reference materials such as GBW07601 human hair, BW3209 and BW3210 environmental water were analyzed, and the results obtained were in good agreement with the certified values provided.

  18. Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia.

    Science.gov (United States)

    Ghobrial, I M; Redd, R; Armand, P; Banwait, R; Boswell, E; Chuma, S; Huynh, D; Sacco, A; Roccaro, A M; Perilla-Glen, A; Noonan, K; MacNabb, M; Leblebjian, H; Warren, D; Henrick, P; Castillo, J J; Richardson, P G; Matous, J; Weller, E; Treon, S P

    2015-12-01

    We examined the combination of the mammalian target of rapamycin inhibitor everolimus with bortezomib and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM) in a phase I/II study. All patients received six cycles of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab followed by maintenance with everolimus until progression. Forty-six patients were treated; 98% received prior rituximab and 57% received prior bortezomib. No dose-limiting toxicities were observed in the phase I. The most common treatment-related toxicities of all grades were fatigue (63%), anemia (54%), leucopenia (52%), neutropenia (48%) and diarrhea (43%). Thirty-six (78%) of the 46 patients received full dose therapy (FDT) of the three drugs. Of these 36, 2 (6%) had complete response (90% confidence interval (CI): 1-16). In all, 32/36 (89%) of patients experienced at least a minimal response (90% CI: 76-96%). The observed partial response or better response rate was 19/36 (53, 90 CI: 38-67%). For the 36 FDT patients, the median progression-free survival was 21 months (95% CI: 12-not estimable). In summary, this study demonstrates that the combination of everolimus, bortezomib and rituximab is well tolerated and achieved 89% response rate even in patients previously treated, making it a possible model of non-chemotherapeutic-based combination therapy in WM.

  19. Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic cancer patients: a phase I-II study.

    Science.gov (United States)

    Stathopoulos, George P; Boulikas, Teni; Vougiouka, Maria; Rigatos, Sotirios K; Stathopoulos, John G

    2006-05-01

    The present trial is a phase I-II study based on a new liposomal cisplatin (lipoplatin). Previous preclinical and clinical data (phase I pharmacokinetics) led to the investigation of a combined treatment modality involving lipoplatin and gemcitabine. The gemcitabine dose was kept standard at 1000 mg/m2 and the lipoplatin dose was escalated from 25 mg/m2 to 125 mg/m2. The treatment was administered to advanced pretreated pancreatic cancer patients who were refractory to previous chemotherapy which included gemcitabine. Lipoplatin at 125 mg/m2 was defined as dose limiting toxicity (DLT) and 100 mg/m2 as the maximum tolerated dose (MTD) in combination with 1000 mg/m2 of gemcitabine. Preliminary objective response rate data showed a partial response in 2/24 patients (8.3%), disease stability in 14 patients (58.3%) for a median duration of 3 months (range 2-7 months) and clinical benefit in 8 patients (33.3%). Liposomal cisplatin is a non-toxic alternative agent to bare cisplatin. In combination with gemcitabine, it has an MTD of 100 mg/m2 and shows promising efficacy in refractory pancreatic cancer.

  20. 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.

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

    CERN Document Server

    Grobler, T G; Wijnholds, S J; Kenyon, J S; Smirnov, O M

    2016-01-01

    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 anti-ghost) symmetrically opposite an unmodelled source around a modelled source. The analysis in the first two papers indicates that the anti-ghost 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 anti-ghost that is $N$-times (where $N$ denotes the numb...

  2. Phase I Clinical Research of Jejunal Interposition in Adenocarcinoma of the Esophagogastric Junction II/III Proximal Gastrectomy

    Directory of Open Access Journals (Sweden)

    Kai Tao

    2016-01-01

    Full Text Available Objective. To investigate the feasibility and specific methods of single-tract jejunal interposition between esophagus and remnant stomach (ers-STJI in adenocarcinoma of the esophagogastric junction (AEG II/III proximal gastrectomy. Methods. 15 AEG II/III gastric cancer (GC patients in phase T1-3N0M0 with tumor size <5 cm were selected and they underwent proximal gastrectomy with ers-STJI from August 2013 to August 2014. Results. All of the 15 patients successfully completed GC R0 proximal gastrectomy with ers-STJI and no operative death or no significant complication occurred; one patient had anastomotic inflammatory granuloma. The digestive tract reconstruction time was 29.5 ± 5.7 min; the intraoperative blood loss was 96.7 ± 20.2 mL, and the number of lymph node dissections was 21.3 ± 3.0; the postoperative flatus time was 48.2 ± 11.9 h; the average length of hospital stay was 10.7 ± 2.3 d, and the average hospital stay cost was 60 ± 3 thousands. All of the patients were followed up for 12 months, and their postoperative single food intake, body weight, hemoglobin, and albumin were all recovered to the preoperative levels. Conclusions. The applications of ers-STJI in proximal gastrectomy were safe and feasible, and the length of jejunal interposition could be 15–25 cm.

  3. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial.

    NARCIS (Netherlands)

    Eggermont, A.M.; Suciu, S.; Santinami, M.; Testori, A.; Kruit, W.H.; Marsden, J.; Punt, C.J.A.; Sales, F.; Gore, M.; Mackie, R.; Kusic, Z.; Dummer, R.; Hauschild, A.; Musat, E.; Spatz, A.; Keilholz, U.

    2008-01-01

    BACKGROUND: Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability. METHODS: 1256 patients with resected stage III melanoma

  4. Methadone induction in primary care (ANRS-Methaville: a phase III randomized intervention trial

    Directory of Open Access Journals (Sweden)

    Roux Perrine

    2012-06-01

    Full Text Available Abstract Background In France, the rapid scale-up of buprenorphine, an opioid maintenance treatment (OMT, in primary care for drug users has led to an impressive reduction in HIV prevalence among injecting drug users (IDU but has had no major effect on Hepatitis C incidence. To date, patients willing to start methadone can only do so in a methadone clinic (a medical centre for drug and alcohol dependence (CSAPA or a hospital setting and are referred to primary care physicians after dose stabilization. This study aims to assess the effectiveness of methadone in patients who initiated treatment in primary care compared with those who initiated it in a CSAPA, by measuring abstinence from street opioid use after one year of treatment. Methods/Design The ANRS-Methaville study is a randomized multicenter non-inferiority control trial comparing methadone induction (lasting approximately 2 weeks in primary care and in CSAPA. The model of care chosen for methadone induction in primary care was based on study-specific pre-training of all physicians, exclusion criteria and daily supervision of methadone during the initiation phase. Between January 2009 and January 2011, 10 sites each having one CSAPA and several primary care physicians, were identified to recruit patients to be randomized into two groups, one starting methadone in primary care (n = 147, the other in CSAPA (n = 48. The primary outcome of the study is the proportion of participants abstinent from street opioids after 1 year of treatment i.e. non-inferiority of primary care model in terms of the proportion of patients not using street opioids compared with the proportion observed in those starting methadone in a CSAPA. Discussion The ANRS-Methaville study is the first in France to use an interventional trial to improve access to OMT for drug users. Once the non-inferiority results become available, the Ministry of Health and agency for the safety of health products may change the the

  5. Site investigation SFR. Fracture mineralogy including identification of uranium phases and hydrochemical characterisation of groundwater in borehole KFR106

    Energy Technology Data Exchange (ETDEWEB)

    Sandstroem, Bjoern [WSP Sverige AB, Goeteborg (Sweden); Nilsson, Kersti [Geosigma AB, Uppsala (Sweden); Tullborg, Eva-Lena [Terralogica AB, Graabo (Sweden)

    2011-12-15

    This report presents the fracture mineralogy and hydrochemistry of borehole KFR106. The most abundant fracture minerals in the examined drill core samples are clay minerals, calcite, quartz and adularia; chlorite is also common but is mostly altered and found interlayered with corrensite. The most common clay mineral is a mixed layer clay consisting of illite-smectite. Pyrite, galena, chalcopyrite, barite (-celestine) and hematite are also commonly found in the fractures, but usually in trace amounts. Other minerals identified in the examined fractures are U-phosphate, pitchblende, U(Ca)-silicate, asphaltite, biotite, monazite, fluorite, titanite, sericite, xenotime, rutile and (Ca, REEs)-carbonate. Uranium has been introduced, mobilised and reprecipitated during at least four different episodes: 1) Originally, during emplacement of U-rich pegmatites, probably as uraninite. 2) At a second event, uranium was mobilised under brittle conditions during formation of breccia/cataclasite. Uraninite was altered to pitchblende and partly coffinitised. Mobilised uranium precipitated as pitchblende closely associated with hematite and chlorite in cataclasite and fracture sealings prior to 1,000 Ma. 3) During the Palaeozoic U was remobilised and precipitated as U-phosphate on open fracture surfaces. 4) An amorphous U-silicate has also been found in open fractures; the age of this precipitation is not known but it is inferred to be Palaeozoic or younger. Groundwater was sampled in two sections in borehole KFR106 with pumping sequences of about 6 days for each section. The samples from sections KFR106:1 and KFR106:2 (260-300 m and 143-259 m borehole length, i.e. -261 and -187 m.a.s.l. mid elevation of the section, respectively) were taken in November 2009 and yielded groundwater chemistry data in accordance with SKB chemistry class 3 and 5. In section KFR106:1 and KFR106:2, the chloride contents were 850 and 1,150 mg/L and the drilling water content 6 and 4%, respectively

  6. Groundwater types in Southeast Srem

    Directory of Open Access Journals (Sweden)

    Gregorić Enike

    2009-01-01

    Full Text Available The region of Southeast Srem is rich in ground waters, which is of great significance to agricultural production. The objective of this paper was to designate the zones of different groundwater types from the aspect of recharge, based on the analysis of groundwater regimes in the study area. A very complex groundwater regime in Southeast Srem, which depends on a great number of natural and some anthropogenic factors, makes it difficult to designate clearly the zones of the three main types of groundwater regime. Still, the boundaries of the zones of groundwater regime types were defined based on the results of correlation analysis of the basic factors affecting the groundwater regime. Zone I includes the climatic type of groundwater. Its fluctuation corresponds to the vertical factors of water balance (precipitation and evaporation and it is not affected by the river water level. This zone extends North and East of the line Putinci, Golubinci, Stara Pazova, Batajnica, Dobanovci, mainly in the area of the loess plateau. Within the zone, groundwater is at a relatively great depth. Only exceptionally, in the valleys, it appears almost on the surface. Zone II includes the climatic-hydrological groundwater type, which is the transition between the climatic type and the hydrological type. The fluctuation of groundwater regime is affected both by the effect of vertical balance factors, and by the effect of watercourses. Climatic-hydrological groundwater type covers the central and the lowest part of the study area and the South part of the middle terrace. Zone III is classified as the hydrological groundwater type and it covers the riparian areas along the Sava and the Danube. The aquifer is hydraulically connected with the river Sava.

  7. 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 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.

  8. Use of concomitant inhaled corticosteroids: pooled data from two phase III studies of aclidinium plus formoterol in COPD.

    Science.gov (United States)

    D'Urzo, Anthony; Singh, Dave; Garcia Gil, Esther

    2017-12-01

    Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease. In some patients, inhaled corticosteroids can be prescribed in combination with bronchodilators. Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use (user vs. non-user), we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease. The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use. We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies. Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users, these data suggest that both groups achieve lung function improvements, which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids.CHRONIC LUNG DISEASE: 'TRIPLE' THERAPY COULD PROVE BENEFICIAL: A dual bronchodilator therapy taken together with corticosteroid inhalers may benefit patients with severe chronic lung disease. Bronchodilator drugs relax the lungs and widen airways in patients with chronic obstructive pulmonary disease (COPD). While recent studies have shown that a dual bronchodilator therapy containing aclidinium and formoterol significantly improves lung function in COPD, little is known about combining the dual therapy with inhaled corticosteroids (ICSs

  9. Groundwater geochemistry of a municipal landfill in Araras, SP

    Directory of Open Access Journals (Sweden)

    Carlos Frederico de Castro Alves 1

    2014-03-01

    Full Text Available A contaminated area associated with a residential unlined landfill, located in Araras, was investigated. The aim of this work was to develop a hydrogeological and geochemical conceptual model in order to identify the redox zones related to the landfill and to explain the main processes resulting from the impact of leachates on the local groundwaters and soil. The work consisted of a surface geological mapping, geophysical survey with electric tomography, logging of subsoil boreholes, an installation of monitoring wells and soil, gas, leachate and groundwater samples analyses. The results show that the Araras landfill is in the methanogenic phase and promotes alterations in local groundwater quality. The main parameters of environmental interest identified in the leachate were total dissolved solids, biochemical oxygen demand, ammonium, methane, Na, Cl, Fe, Mn, Ba, B, Co and Cd. According to criteria specifically developed for this landfill, the following redox zones were identified in the groundwater: (i aerobic, located upgradient from the landfill; (ii methanogenic, downgradient from the landfill; (iii iron and/or manganese reduction, located between the methanogenic zone and the Araras river. Bypassing the iron and/or manganese redox zone, the existence of a denitrification zone was inferred. Besides the redox reactions in these zones, other processes that mitigate the impact of leachate into groundwater were also discovered: dilution, degradation by the action of surface microorganisms, dispersion, ionic exchange, formation of organic and inorganic complexes, dissolution and precipitation.

  10. Balloon catheter hypoxic pelvic perfusion with mitomycin C and melphalan for locally advanced tumours in the pelvic region : A phase I-II trial

    NARCIS (Netherlands)

    van Ijken, MGA; van Etten, B; Guetens, G; de Bruijn, EA; ten Hagen, TLM; Wiggers, T; Eggermont, AMM

    2005-01-01

    Aims: To investigate the feasibility of hypoxic pelvic perfusion (HPP), using balloon catheter techniques as treatment modality for locally advanced pelvic malignancies. Methods: In a phase I-II study, 16 patients with various non-resectabte pelvic tumours were treated with two HIPP with MMC and mel

  11. Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial.

    NARCIS (Netherlands)

    Janssens, G.O.R.J.; Terhaard, C.H.J.; Doornaert, P.A.; Bijl, H.P.; Ende, P. van den; Chin, A.; Pop, L.A.M.; Kaanders, J.H.A.M.

    2012-01-01

    PURPOSE: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. METHODS AND MATERIALS: From April 2001 to February 2008, 345 patients with

  12. ACUTE TOXICITY PROFILE AND COMPLIANCE TO ACCELERATED RADIOTHERAPY PLUS CARBOGEN AND NICOTINAMIDE FOR CLINICAL STAGE T2-4 LARYNGEAL CANCER : RESULTS OF A PHASE III RANDOMIZED TRIAL

    NARCIS (Netherlands)

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; van den Ende, Piet; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-01-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with

  13. 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 s...

  14. Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine monoclonal antibody in patients with epithelial ovarian cancer after a surgically defined complete remission.

    NARCIS (Netherlands)

    Verheijen, R.H.; Massuger, L.F.A.G.; Benigno, B.B.; Epenetos, A.A.; Lopes, A.; Soper, J.T.; Markowska, J.; Vyzula, R.; Jobling, T.; Stamp, G.; Spiegel, G.; Thurston, D.; Falke, T.; Lambert, J.; Seiden, M.V.

    2006-01-01

    PURPOSE: This was a multinational, open-label, randomized phase III trial comparing yttrium-90-labeled murine HMFG1 (90Y-muHMFG1) plus standard treatment versus standard treatment alone in patients with epithelial ovarian cancer (EOC) who had attained a complete clinical remission after

  15. Talactoferrin in Severe Sepsis: Results From the Phase II/III Oral tAlactoferrin in Severe sepsIS Trial

    NARCIS (Netherlands)

    Vincent, J.L.; Marshall, J.C.; Dellinger, R.P.; Simonson, S.G.; Guntupalli, K.; Levy, M.M.; Singer, M.; Malik, R.; Pickkers, P.

    2015-01-01

    OBJECTIVE: Talactoferrin alfa is a recombinant form of the human glycoprotein, lactoferrin, which has been shown to have a wide range of effects on the immune system. This phase II/III clinical trial compared talactoferrin with placebo, in addition to standard of care, in patients with severe sepsis

  16. Topical report on subsurface fracture mapping from geothermal wellbores. Phase I. Pulsed radar techniques. Phase II. Conventional logging methods. Phase III. Magnetic borehole ranging

    Energy Technology Data Exchange (ETDEWEB)

    Hartenbaum, B.A.; Rawson, G.

    1980-09-01

    To advance the state-of-the-art in Hot Dry Rock technology, an evaluation is made of (i) the use of radar to map far-field fractures, (ii) the use of more than twenty different conventional well logging tools to map borehole-fracture intercepts, and (iii) the use of magnetic dipole ranging to determine the relative positions of the injection well and the production well within the fractured zone. It is found that according to calculations, VHF backscatter radar has the potential for mapping fractures within a distance of 50 +- 20 meters from the wellbore. A new technique for improving fracture identification is presented. Analyses of extant data indicate that when used synergistically the (1) caliper, (2) resistivity dipmeter, (3) televiewer, (4) television, (5) impression packer, and (6) acoustic transmission are useful for mapping borehole-fracture intercepts. Improvements in both data interpretation techniques and high temperature operation are required. The surveying of one borehole from another appears feasible at ranges of up to 200 to 500 meters by using a low frequency magnetic field generated by a moderately strong dipole source (a solenoid) located in one borehole, a sensitive B field detector that traverses part of the second borehole, narrow band filtering, and special data inversion techniques.

  17. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial.

    Science.gov (United States)

    Knauf, Wolfgang U; Lissitchkov, Toshko; Aldaoud, Ali; Liberati, Anna M; Loscertales, Javier; Herbrecht, Raoul; Juliusson, Gunnar; Postner, Gerhard; Gercheva, Liana; Goranov, Stefan; Becker, Martin; Fricke, Hans-Joerg; Huguet, Francoise; Del Giudice, Ilaria; Klein, Peter; Merkle, Karlheinz; Montillo, Marco

    2012-10-01

    The efficacy of bendamustine versus chlorambucil in a phase III trial of previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia (CLL) was re-evaluated after a median observation time of 54 months in May 2010. Overall survival (OS) was analysed for the first time. At follow-up, investigator-assessed complete response (CR) rate (21·0% vs 10·8%), median progression-free survival (21·2 vs 8·8 months; P chlorambucil. OS was not different between groups for all patients or those ≤65 years, >65 years, responders and non-responders. However, patients with objective response or a CR experienced a significantly longer OS than non-responders or those without a CR. Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine (78·3% vs 63·6%; P = 0·004). The benefits of bendamustine over chlorambucil were achieved without reducing quality of life. In conclusion, bendamustine is significantly more effective than chlorambucil in previously untreated CLL patients, with the achievement of a CR or objective response appearing to prolong OS. Bendamustine should be considered as a preferred first-line option over chlorambucil for CLL patients ineligible for fludarabine, cyclophosphamide and rituximab. © 2012 Blackwell Publishing Ltd.

  18. Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results From an International, Phase III Clinical Trial.

    Science.gov (United States)

    Kane, John M; Zukin, Stephen; Wang, Yao; Lu, Kaifeng; Ruth, Adam; Nagy, Krisztián; Laszlovszky, István; Durgam, Suresh

    2015-08-01

    This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P effective treatment for schizophrenia.

  19. Flexible selection of a single treatment incorporating short-term endpoint information in a phase II/III clinical trial.

    Science.gov (United States)

    Stallard, Nigel; Kunz, Cornelia Ursula; Todd, Susan; Parsons, Nicholas; Friede, Tim

    2015-10-15

    Seamless phase II/III clinical trials in which an experimental treatment is selected at an interim analysis have been the focus of much recent research interest. Many of the methods proposed are based on the group sequential approach. This paper considers designs of this type in which the treatment selection can be based on short-term endpoint information for more patients than have primary endpoint data available. We show that in such a case, the familywise type I error rate may be inflated if previously proposed group sequential methods are used and the treatment selection rule is not specified in advance. A method is proposed to avoid this inflation by considering the treatment selection that maximises the conditional error given the data available at the interim analysis. A simulation study is reported that illustrates the type I error rate inflation and compares the power of the new approach with two other methods: a combination testing approach and a group sequential method that does not use the short-term endpoint data, both of which also strongly control the type I error rate. The new method is also illustrated through application to a study in Alzheimer's disease. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  20. Impact of ixekizumab on psoriasis itch severity and other psoriasis symptoms: Results from 3 phase III psoriasis clinical trials.

    Science.gov (United States)

    Kimball, Alexandra B; Luger, Thomas; Gottlieb, Alice; Puig, Luis; Kaufmann, Roland; Nikaï, Enkeleida; Zhu, Baojin; Edson-Heredia, Emily; Carlier, Hilde; Lin, Chen-Yen; Goldblum, Orin; Yosipovitch, Gil

    2016-12-01

    Itch is a prevalent symptom of psoriasis that impacts quality of life. We sought to describe improvements in itch severity, skin pain, and bothersomeness of skin appearance caused by psoriasis among patients who received ixekizumab, etanercept, or placebo in three 12-week, phase III clinical trials (UNCOVER-1, -2, and -3). The itch numeric rating scale evaluated psoriasis itch severity in all 3 trials. Skin pain was assessed by skin pain visual analog scale. Bothersomeness because of redness/discoloration, thickness, and scaling/flaking was assessed with the Psoriasis Skin Appearance Bothersomeness instrument. Psoriasis skin appearance bothersomeness and skin pain were assessed at baseline and week 12; itch numeric rating scale score was assessed at baseline and weeks 1, 2, 4, 8, and 12. Patients who received ixekizumab demonstrated statistically significant improvements (P psoriasis symptom improvement with ixekizumab treatment are needed. After treatment with ixekizumab, patients reported fast, significant, and clinically meaningful improvements in itch severity and other psoriasis-related symptoms such as skin pain and skin appearance bothersomeness. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. 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 journal being ICMJE-affiliated (49.3 vs 40 %; p journal not being affiliated with ICMJE (36.9 vs 21.3 %; p < 0.001). Of the published studies we investigated, over half did not disclose 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.

  2. 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.

  3. 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.

  4. Parametric Dose Standardization for Optimizing Two-Agent Combinations in a Phase I-II Trial with Ordinal Outcomes.

    Science.gov (United States)

    Thall, Peter F; Nguyen, Hoang Q; Zinner, Ralph G

    2017-01-01

    A Bayesian model and design are described for a phase I-II trial to jointly optimise the doses of a targeted agent and a chemotherapy agent for solid tumors. A challenge in designing the trial was that both the efficacy and toxicity outcomes were defined as four-level ordinal variables. To reflect possibly complex joint effects of the two doses on each of the two outcomes, for each marginal distribution a generalised continuation ratio model was assumed, with each agent's dose parametrically standardised in the linear term. A copula was assumed to obtain a bivariate distribution. Elicited outcome probabilities were used to construct a prior, with variances calibrated to obtain small prior effective sample size. Elicited numerical utilities of the 16 elementary outcomes were used to compute posterior mean utilities as criteria for selecting dose pairs, with adaptive randomisation to reduce the risk of getting stuck at a suboptimal pair. A simulation study showed that parametric dose standardisation with additive dose effects provides a robust, reliable model for dose pair optimisation in this setting, and it compares favourably with designs based on alternative models that include dose-dose interaction terms. The proposed model and method are applicable generally to other clinical trial settings with similar dose and outcome structures.

  5. Progress Toward Cleanup of Operable Unit 1 Groundwater at the US DOE Mound, Ohio, Site: Success of a Phase-Combined Remedy – 15310

    Energy Technology Data Exchange (ETDEWEB)

    Hooten, Gwendolyn [U.S. Department of Energy, Harrison, OH (United States). Office of Legacy Management; Cato, Rebecca [Stoller Newport News Nuclear Inc., Weldon Spring, MS (United States); Looney, Brian [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Huntsman, Brent [Terran Corporation, Beavercreek, OH (United States)

    2015-03-01

    Operable Unit 1 (OU-1) soil and groundwater have been affected by volatile organic compounds (VOC) Present groundwater remedy is collection, treatment, and disposal (pump and treat [P&T]) Several combinations of technologies were used to address soil and groundwater contamination Monitored natural attenuation (MNA) is a viable alternative Majority of source term has been excavated VOC concentrations in groundwater have decreased Attenuation mechanisms have been observed in the subsurface at OU-1

  6. The influence of interfacial properties on the two-phase liquid flow of organic contaminants in groundwater. Final report, July 1, 1989--June 30, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Demond, A.H.; Desai, F.N.; Hayes, K.F.

    1992-12-31

    DOE`s waste sites are contaminated with a variety of organic liquids. Because of their low solubility in water, organic liquids such as these will persist as separate liquid phases and be transported as such in the subsurface. Thus, an improved understanding of the factors influencing the movement of a separate organic liquid phase in the subsurface is important to DOE`s efforts to control groundwater contamination. Wettability is sometimes cited as the most important factor influencing two-phase flow in porous media. The wetting phase migrates preferentially through the smaller pores, whereas the nonwetting phase is concentrated in the larger pores. Typically, aquifers are thought of as strongly water-wet, implying that the organic liquid preferentially occupies the larger pores. But in fact, that state depends on the properties of the three interfaces of the system: between the organic liquid and water, water and the solid, and the organic liquid and the solid. Characteristics of the system which affect the interfacial properties also impact the wettability, such as the nature of the aquifer solids` surfaces, the composition of the goundwater and the properties of the organic contaminant. The alteration of wettability at DOE waste sites may be dominated by the presence of co-contaminants such as organic acids and bases which behave as surface-active agents or surfactants. Because of their physicochemical nature, surfactants will sorb preferentially at the interfaces of the system, thereby impacting the wettability and the distribution of the liquids in the porous medium. The over-all objective of this research was to determine how changes in interfacial properties affect two-phase flow. Specifically, the objective was to examine the effect of surfactant sorption on capillary pressure relationships by correlating measurements of sorption, zeta potential, interfacial tension and contact angle, with changes in the capillary pressure-saturation relationships.

  7. Evaluation of Elevated Tritium Levels in Groundwater Downgradient from the 618-11 Burial Ground Phase I Investigations

    Energy Technology Data Exchange (ETDEWEB)

    Dresel, P.E.; Smith, R.M.; Williams, B.A.; Thompson, C.J.; Evans, J.C.; Hulstrom, L.C.

    2000-05-01

    This report describes the results of the preliminary investigation of elevated tritium in groundwater discovered near the 618-11 burial ground, located in the eastern part of the Hanford Site. Tritium in one well downgradient of the burial ground was detected at levels up to 8,140,000 pCi/L. The 618-11 burial ground received a variety of radioactive waste from the 300 Area between 1962 and 1967. The burial ground covers 3.5 hectare (8.6 acre) and contains trenches, large diameter caissons, and vertical pipe storage units. The burial ground was stabilized with a native sediment covering. The Energy Northwest reactor complex was constructed immediately east of the burial ground.

  8. Epitaxial growth of III-V nitrides and phase separation and ordering in indium gallium nitride alloys

    Science.gov (United States)

    Doppalapudi, Dharanipal

    The family of III-V nitrides are wide band-gap semiconductors with a broad range of opto-electronic applications in LEDs, laser diodes, UV detectors as well as high temperature/high frequency devices. Due to the lack of good quality native substrates, GaN is grown on foreign substrates that have a lattice and thermal mismatch with GaN. This results in a material with a high density of defects, which in turn adversely affects the opto-electronic properties of the epilayer. In this study, GaN films were epitaxially grown on various substrates (C-plane sapphire, A-plane sapphire, SiC and ZnO) by molecular beam epitaxy. Additionally, GaN homoepitaxy onto laterally overgrown thick GaN substrates was investigated. It was demonstrated that the polarity of the GaN film plays a major role in determining the properties of the films. The growth parameters were optimized to eliminate inversion domain boundaries, which result in domains of opposite polarity in the GaN lattice. For growth on A-plane sapphire, it was found that substrate nitridation and low temperature buffer deposition are critical in order to obtain good epitaxial growth, in spite of the relatively small mismatch between the film and substrate. A crystallographic model was developed to explain this observation. By optimizing growth parameters, GaN films with excellent structural, transport, optical and device properties were grown. The second part of this research involves growth of ternary alloys and superlattice structures, which are essential in the fabrication of many devices. It was found that the InN-GaN pseudo-binary system is not homogeneous over the entire composition range. Due to the mismatch between the tetrahedral radii of GaN and InN, InGaN alloys exhibited phase separation and long-range atomic ordering. Investigations of InxGa1-xN films grown over a wide range of compositions by XRD and TEM showed that the predominant strain relieving mechanism was phase separation in films with x > 0.2, and

  9. Groundwater degassing and two-phase flow in fractured rock: Summary of results and conclusions achieved during the period 1994-2000

    Energy Technology Data Exchange (ETDEWEB)

    Jarsjoe, J.; Destouni, G. [Royal Inst. of Technology, Stockholm (Sweden). Water Resources Engineering; Gale, J. [Fracflow Consultants Inc., (Canada)

    2001-06-01

    Although water saturated conditions generally prevail several hundreds of metres below the ground water table, two-phase flow conditions, i.e. a mixed flow of gas and water, may develop in the vicinity of a repository situated in a regionally saturated rock mass. Deep groundwater naturally contains dissolved gases that may come out of solution if the water pressure is reduced to atmospheric pressure in the vicinity of boreholes and drifts, for instance, during hydraulic and tracer testing. Under certain conditions, this may lead to development of an unsaturated zone, affecting the local hydrology. Other possible sources of two-phase flow conditions in the vicinity of a deep repository include air entry in connection with tunnel ventilation and gas generation in the repository due to corrosion or biological processes. Quantitative two-phase flow models are needed in order to investigate the potential effects of all the above processes. However, traditional constitutive relations for two-phase/unsaturated flow were developed for porous media and are based on parameters that can be readily estimated in soil, but are difficult or impossible to determine independently in fractured rock. Despite the parameter estimation difficulties, several studies have indicated that these relations can be calibrated to reproduce observed unsaturated fracture flow behaviour. In this report, we show that a novel, fractured rock relation is at least equally capable of calibrated reproduction of unsaturated fracture flow as the widely used van Genuchten relation for porous media. Moreover, due to the fact that the novel relation is based on parameters that are physically relevant for (and independently measurable in) rock fractures in the field, it has the potential of independent prediction capabilities, which is not the case for the van Genuchten relation. We furthermore consider in detail the effects of groundwater degassing on measurements of hydraulic properties in boreholes and

  10. Observation Targeting for the Tehachapi Pass and Mid-Columbia Basin: WindSENSE Phase III Project Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Hanley, D

    2011-10-22

    The overall goal of this multi-phased research project known as WindSENSE is to develop an observation system deployment strategy that would improve wind power generation forecasts. The objective of the deployment strategy is to produce the maximum benefit for 1- to 6-hour ahead forecasts of wind speed at hub-height ({approx}80 m). In Phase III of the project, the focus was on the Mid-Columbia Basin region which encompasses the Bonneville Power Administration (BPA) wind generation area shown in Figure 1 that includes Klondike, Stateline, and Hopkins Ridge wind plants. The typical hub height of a wind turbine is approximately 80-m above ground level (AGL). So it would seem that building meteorological towers in the region upwind of a wind generation facility would provide data necessary to improve the short-term forecasts for the 80-m AGL wind speed. However, this additional meteorological information typically does not significantly improve the accuracy of the 0- to 6-hour ahead wind power forecasts because processes controlling wind variability change from day-to-day and, at times, from hour-to-hour. It is also important to note that some processes causing significant changes in wind power production function principally in the vertical direction. These processes will not be detected by meteorological towers at off-site locations. For these reasons, it is quite challenging to determine the best type of sensors and deployment locations. To address the measurement deployment problem, Ensemble Sensitivity Analysis (ESA) was applied in the Phase I portion of the WindSENSE project. The ESA approach was initially designed to produce spatial fields that depict the sensitivity of a forecast metric to a set of prior state variables selected by the user. The best combination of variables and locations to improve the forecast was determined using the Multiple Observation Optimization Algorithm (MOOA) developed in Phase I. In Zack et al. (2010a), the ESA-MOOA approach was

  11. Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part)

    National Research Council Canada - National Science Library

    Vermorken, J B; Peyrade, F; Krauss, J; Mesía, R; Remenar, E; Gauler, T C; Keilholz, U; Delord, J P; Schafhausen, P; Erfán, J; Brümmendorf, T H; Iglesias, L; Bethe, U; Hicking, C; Clement, P M

    2014-01-01

    ... αvβ3 and αvβ5 integrins and is investigated as a treatment strategy. The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN...

  12. SCORE2 Report 1: Techniques to Optimize Recruitment in Phase III Clinical Trials of Patients With Central Retinal Vein Occlusion.

    Science.gov (United States)

    Scott, Ingrid U; VanVeldhuisen, Paul C; Ip, Michael S; Blodi, Barbara A; Oden, Neal L; Figueroa, Maria

    2016-10-01

    To investigate recruitment rates of patients with central retinal vein occlusion (CRVO) into phase III clinical trials evaluating intravitreal pharmacotherapy for treatment of macular edema in the United States, describe recruitment techniques in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2), and assess which SCORE2 recruitment techniques were most useful to principal investigators and clinical coordinators. Retrospective survey within a randomized clinical trial. Recruitment rates of the Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE)-CRVO trial, CRUISE Study, and SCORE2 were calculated. Techniques employed to facilitate recruitment in SCORE2 are described, and a survey was sent to the principal investigator and primary clinical coordinator of each SCORE2 site to assess the usefulness of recruitment techniques. In SCORE2, the recruitment rate of 0.39 participants/month/site was higher than in SCORE-CRVO (0.10 participants/month/site) and CRUISE (0.23 participants/month/site). For study design factors in SCORE2, investigators and coordinators rated provision of standard-of-care treatments to all study participants as having a major positive impact on recruitment. A monthly e-newsletter to site staff and communication by physician members of the SCORE2 Executive Committee to sites upon each randomization were perceived as effective means to help site staff focus on recruitment. The SCORE2 recruitment rate compares favorably to previous clinical trials investigating intravitreal pharmacotherapy for treatment of CRVO-associated macular edema. Study design factors, methods of communication with sites, and recruitment techniques implemented in SCORE2 were well received by investigators and coordinators and may be helpful in future clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Tai Chi as an adjunct physical activity for adults aged 45 years and older enrolled in phase III cardiac rehabilitation.

    Science.gov (United States)

    Taylor-Piliae, Ruth E; Silva, Edna; Sheremeta, Sharon Peachey

    2012-03-01

    Cardiac rehabilitation improves physical, cognitive and psychosocial functioning, yet services are greatly underutilized with increasing patterns of attrition over time. Tai Chi has been suggested as a possible adjunct to cardiac rehabilitation exercise training. To describe differences in physical, cognitive and psychosocial functioning among adults ≥ 45 years old attending phase III cardiac rehabilitation, who have or have not self-selected Tai Chi exercise as an adjunct physical activity. A cross-sectional design compared subjects attending group-based Wu style Tai Chi classes plus cardiac rehabilitation, with cardiac rehabilitation only. Subjects had a battery of physical and cognitive functioning tests administered to examine aerobic endurance, balance, strength, and flexibility, verbal retrieval/recall, attention, concentration and tracking. Subjects completed a health survey to ascertain cardiac event information, medical history, and psychosocial functioning (i.e. health-related quality of life, stress, depressive symptoms, social support, and Tai Chi self-efficacy). A total of 51 subjects (75% married, 84% college-educated, 96% White/European-American) participated. Subjects were on average 70 (± 8) years old and had attended cardiac rehabilitation for 45 (± 37) months. Approximately 45% (n = 23) attended Tai Chi classes plus cardiac rehabilitation, while 55% (n = 28) attended cardiac rehabilitation only. Subjects attending Tai Chi plus cardiac rehabilitation had better balance, perceived physical health, and Tai Chi self-efficacy compared to those attending cardiac rehabilitation only (p ≤ 0.03). Tai Chi can be easily implemented in any community/cardiac rehabilitation facility, and may offer adults additional options after a cardiac event.

  14. Phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate in dogs with naturally occurring malignant tumors.

    Science.gov (United States)

    Cai, Shuang; Zhang, Ti; Forrest, W C; Yang, Qiuhong; Groer, Chad; Mohr, Eva; Aires, Daniel J; Axiak-Bechtel, Sandra M; Flesner, Brian K; Henry, Carolyn J; Selting, Kimberly A; Tate, Deborah; Swarz, Jeffrey A; Bryan, Jeffrey N; Forrest, M Laird

    2016-09-01

    OBJECTIVE To conduct a phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate (HA-Pt) in dogs with naturally occurring malignant tumors. ANIMALS 18 healthy rats, 9 healthy mice, and 16 dogs with cancer. PROCEDURES HA-Pt was prepared and tested by inductively coupled plasma mass spectrometry; DNA-platinum adduct formation and antiproliferation effects of cisplatin and HA-Pt were compared in vitro. Effects of cisplatin (IV) and HA-Pt (SC) in rodents were tested by clinicopathologic assays. In the clinical trial, dogs with cancer received 1 to 4 injections of HA-Pt (10 to 30 mg/m(2), intratumoral or peritumoral, q 3 wk). Blood samples were collected for pharmacokinetic analysis; CBC, serum BUN and creatinine concentration measurement, and urinalysis were conducted before and 1 week after each treatment. Some dogs underwent hepatic enzyme testing. Tumors were measured before the first treatment and 3 weeks after each treatment to assess response. RESULTS No adverse drug effects were detected in pretrial assessments in rodents. Seven of 16 dogs completed the study; 3 had complete tumor responses, 3 had stable disease, and 1 had progressive disease. Three of 7 dogs with oral and nasal squamous cell carcinoma (SCC) that completed the study had complete responses. Myelosuppression and cardiotoxicosis were identified in 6 and 2 dogs, respectively; none had nephrotoxicosis. Four of 5 dogs with hepatic enzymes assessed had increased ALT activities, attributed to diaquated cisplatin products in the HA-Pt. Pharmacokinetic data fit a 3-compartment model. CONCLUSIONS AND CLINICAL RELEVANCE HA-Pt treatment resulted in positive tumor responses in some dogs, primarily those with SCC. The adverse effect rate was high. IMPACT FOR HUMAN MEDICINE Oral SCC in dogs has characteristics similar to human head and neck SCC; these results could be useful in developing human treatments.

  15. Efficacy and tolerability of fesoterodine in men with overactive bladder: a pooled analysis of 2 phase III studies.

    Science.gov (United States)

    Herschorn, Sender; Jones, J Stephen; Oelke, Matthias; MacDiarmid, Scott; Wang, Joseph T; Guan, Zhonghong

    2010-05-01

    To assess the efficacy, safety, and tolerability of fesoterodine 4 and 8 mg in men with overactive bladder. This was a subanalysis of pooled data from 358 men enrolled in 2 double-blind, placebo-controlled phase III trials. Subjects with frequency and urgency or urgency urinary incontinence (UUI) were randomized to fesoterodine 4 mg, fesoterodine 8 mg, or placebo for 12 weeks. Efficacy endpoints included bladder diary variables and subject-reported treatment response. By week 12, men treated with fesoterodine 4 or 8 mg had significantly greater median percentage improvements in micturition frequency, urgency episodes, and UUI episodes versus placebo and significantly greater percentages reported a treatment response versus placebo. Significant increases in mean voided volume (MVV) per micturition versus placebo occurred with fesoterodine 8 mg only. At week 12, fesoterodine 8 mg was significantly more efficacious than fesoterodine 4 mg in improving UUI episodes and MVV per micturition. The most commonly reported adverse events with fesoterodine 4 and 8 mg were dry mouth (12.5% and 37.7% vs 5.6% with placebo) and constipation (2.5% and 8.8% vs 0.8% with placebo). Symptoms suggestive of urinary retention were reported in 0.8%, 0.8%, and 5.3% of men in the placebo, fesoterodine 4 mg, and fesoterodine 8 mg groups, respectively; only 1 subject, in the fesoterodine 8 mg group, was catheterized. Fesoterodine 4 and 8 mg are generally safe, efficacious, and well tolerated for the treatment of overactive bladder symptoms in men. The 8 mg dose provides additional benefit and allows for treatment individualization. Copyright 2010 Elsevier Inc. All rights reserved.

  16. 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.

  17. 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.

  18. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.

    Science.gov (United States)

    Pujade-Lauraine, Eric; Hilpert, Felix; Weber, Béatrice; Reuss, Alexander; Poveda, Andres; Kristensen, Gunnar; Sorio, Roberto; Vergote, Ignace; Witteveen, Petronella; Bamias, Aristotelis; Pereira, Deolinda; Wimberger, Pauline; Oaknin, Ana; Mirza, Mansoor Raza; Follana, Philippe; Bollag, David; Ray-Coquard, Isabelle

    2014-05-01

    In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. Eligible patients had measurable/assessable OC that had progressed two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.

  19. Effects of interleukin-3 following chemotherapy of non-Hodgkin's lymphoma. A prospective, controlled phase I/II study.

    Science.gov (United States)

    Hovgaard, D J; Nissen, N I

    1995-02-01

    The effect of rhIL-3 was investigated in 32 patients with newly diagnosed non-Hodgkin lymphoma in a phase I/II trial. All patients received 6 cycles of standard CHOP chemotherapy, and each patient was his own control where rhIL-3 was given as a daily s.c. injection for 14 days (day 2-15) in cycle 2 and 4, while cycle 1 and 3 were control cycles. Five dose levels were examined (0.5 - 1 - 5 - 7.5 - 10 micrograms/kg). Compared to the other more lineage-specific hemopoietic growth factors G- and GM-CSF, the effect of rhIL-3 on the hemopoiesis was less dramatic and more delayed, i.e. the most apparent effect was observed in the 2 weeks of treatment. Thus, the neutrophil counts from days 15 to 22 following CHOP were significantly raised and the duration of neutropenia was shorter (significantly only at 10 micrograms/kg), while the nadir values were unaffected. Platelet recovery from days 12-22 was significantly increased and nadir values occurred earlier compared to control cycles, but were only increased in some subsets. Other cell populations affected moderately in the recovery period were eosinophils and monocytes. Reticulocytes increased, but no effect on hemoglobin or RBC transfusion requirement was noted. Only moderate adverse reactions occurred such as fever, chills, flushing of the face and flu-like symptoms. There was no evidence of stimulation of tumor growth. Most significant, the rhIL-3 treatment at all but the lowest dose levels led to an improved tolerance to chemotherapy, as indicated by a decline in number of delayed cycles. A conclusion concerning the role of rhIL-3 as post-chemotherapy adjuvant should await studies using rhIL-3 in combination with more lineage-restricted hemopoietic growth factors.

  20. A phase III randomised controlled trial of single-dose triple therapy in COPD: the IMPACT protocol.

    Science.gov (United States)

    Pascoe, Steven J; Lipson, David A; Locantore, Nicholas; Barnacle, Helen; Brealey, Noushin; Mohindra, Rajat; Dransfield, Mark T; Pavord, Ian; Barnes, Neil

    2016-08-01

    Patients with symptomatic advanced chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations are particularly at risk of poor outcomes and present a significant burden on healthcare systems. The relative merits of treating with different inhaled combination therapies e.g. inhaled corticosteroids (ICS)/long-acting β2-agonist (LABA), LABA/long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, in this patient group are poorly understood, as is reflected in current guidelines. The InforMing the PAthway of COPD Treatment (IMPACT) study will evaluate the efficacy and safety of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI over a 52-week treatment period. The study has been designed with a focus on understanding the comparative merits of each treatment modality in different phenotypes/endotypes.This is a phase III, randomised, double-blind, three-arm, parallel-group, global multicentre study comparing the rate of moderate and severe exacerbations between FF/UMEC/VI and FF/VI or UMEC/VI over a 52-week treatment period. The study aims to recruit 10 000 patients from approximately 1070 centres. Eligible patients are aged ≥40 years, with symptomatic advanced COPD (Global initiative for chronic Obstructive Lung Disease (GOLD) group D) and an exacerbation in the previous 12 months.The first patients were recruited to the IMPACT study (ClinicalTrials.gov: NCT02164513) in June 2014 and the anticipated completion date is July 2017. Copyright ©ERS 2016.

  1. 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.

  2. Survival Outcomes of Sipuleucel-T Phase III Studies: Impact of Control-Arm Cross-Over to Salvage Immunotherapy.

    Science.gov (United States)

    George, Daniel J; Nabhan, Chadi; DeVries, Todd; Whitmore, James B; Gomella, Leonard G

    2015-09-01

    Sipuleucel-T is an autologous cellular immunotherapy for asymptomatic/minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC). After disease progression, control-arm patients on three double-blind, randomized phase III sipuleucel-T trials were offered, in nonrandomized open-label protocols, APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control manufacture. These exploratory analyses evaluated potential effects on survival outcomes associated with such treatment. Of 249 control-treated patients, 165 (66.3%) received APC8015F. We explored the effects of APC8015F on the overall survival (OS; Cox regression) of control-arm patients and treatment effects of sipuleucel-T versus control adjusted for APC8015F treatment [iterative parameter estimation model (IPE)]. The median time to first APC8015F infusion was 5.2 months (range, 1.8-33.1) after randomization and 2.2 months (0.5-14.6) after progression. After disease progression, median survival was longer for APC8015F-treated versus control-only treated patients [20.0 vs. 9.8 months; HR, 0.53; 95% confidence interval (CI), 0.38-0.74; P sipuleucel-T versus control adjusted for APC8015F treatment was 3.9 months if APC8015F had no effect and was 8.1 months if APC8015F was equally as effective as sipuleucel-T. Exploratory analyses indicate that APC8015F treatment may have extended patient survival, suggesting the sipuleucel-T OS advantage in CRPC may be more robust than previously estimated.

  3. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120770.

  4. 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.

  5. Direct speciation analysis of thallium based on solid phase extraction and specific retention of a Tl(III) complex on alumina coated with sodium dodecyl sulfate.

    Science.gov (United States)

    Biaduń, Ewa; Sadowska, Monika; Ospina-Alvarez, Natalia; Krasnodębska-Ostręga, Beata

    Alumina (Al2O3) with an average particle size of 63 μm was modified with the anionic surfactant sodium dodecyl sulfate (SDS) and then applied to (i) solid phase extraction and separation of both thallium(I) and thallium(III), and (ii) preconcentration of Tl(III) from waste water samples. Only Tl(III), in the form of its complex with diethylenetriaminepentaacetate (DTPA), was retained on the sorbent, from where it can be eluted with 40 % nitric acid. Thallium species were then quantified by ICP MS. The method was characterized by a LOD of 25 pg of Tl(I) and 160 pg of Tl(III) in 10 mL samples. A large excesses of Tl(I) over Tl(III) was tolerated, and relatively high levels of other metal ions, such as a 500-fold excess of Pb(II) and Cd(II), and a 2000-fold excess of Zn(II), respectively, do not interfere. The sorbent was easily prepared and possesses a high loading capacity, and these properties make it an attractive material for rapid and efficient extraction and speciation of Tl. Graphical abstract:Schematic of the SPE procedure for separation (with preconcentration) of Tl(III) from Tl(I) was developed and applied to direct speciation analysis of thallium in wastewater. Self-made columns packed with alumina coated with SDS were used. The method is resistant to interferences from Pb, Cd, Zn and tolerates a large excess of Tl(I) over Tl(III).

  6. Analysis of trace levels of sulfonamide and tetracycline antimicrobials in groundwater and surface water using solid-phase extraction and liquid chromatography/mass spectrometry

    Science.gov (United States)

    Lindsey, M.E.; Meyer, M.; Thurman, E.M.

    2001-01-01

    A method has been developed for the trace analysis of two classes of antimicrobials consisting of six sulfonamides (SAs) and five tetracyclines (TCs), which commonly are used for veterinary purposes and agricultural feed additives and are suspected to leach into ground and surface water. The method used solid-phase extraction and liquid chromatography/mass spectrometry (LC/MS) with positive ion electrospray. The unique combination of a metal chelation agent (Na2EDTA) with a macroporous copolymer resulted in quantitative recoveries by solid-phase extraction (mean recovery, 98 ?? 12%) at submicrogram-per-liter concentrations. An ammonium formate/formic acid buffer with a methanol/water gradient was used to separate the antimicrobials and to optimize the signal intensity. Mass spectral fragmentation and ionization characteristics were determined for each class of compounds for unequivocal identification. For all SAs, a characteristic m/z 156 ion representing the sulfanilyl fragment was identified. TCs exhibited neutral losses of 17 amu resulting from the loss of ammonia and 35 amu from the subsequent loss of water. Unusual matrix effects were seen only for TCs in this first survey of groundwater and surface water samples from sites around the United States, requiring that TCs be quantitated using the method of standard additions.

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

    DEFF Research Database (Denmark)

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

    1990-01-01

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

  8. Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study

    OpenAIRE

    Kimihiro Okubo; Minoru Gotoh; Mikiya Asako; Yasuyuki Nomura; Michinori Togawa; Akihiro Saito; Takayuki Honda; Yoshihiro Ohashi

    2017-01-01

    Background: Bilastine, a novel non-sedating second-generation H1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). Methods: This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexo...

  9. Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis

    OpenAIRE

    Miller, Aaron E.; O’Connor, Paul; Wolinsky, Jerry S.; Confavreux, Christian; Kappos, Ludwig; Olsson, Tomas P.; Truffinet, Philippe; Wang, Lin; D’Castro, Laura; Comi, Giancarlo; Freedman, Mark S; ,

    2012-01-01

    Background: The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients. Objective: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified s...

  10. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

    OpenAIRE

    Schuler, M.; Yang, J. C.-H.; Park, K.; Kim, J. -H.; Bennouna, J; Chen, Y.-M.; Chouaid, C.; de Marinis, F.; Feng, J. -F.; Grossi, F; Kim, D.-W.; Liu, X.; Lu, S.; Strausz, J.; Vinnyk, Y.

    2015-01-01

    Background Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. Patients and methods Patients with relapsed/refractory disease following ≥1 ...

  11. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

    OpenAIRE

    Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina

    2016-01-01

    Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethaso...

  12. Intermolecular proton transfer in solid phase: a rare example of crystal-to-crystal transformation from hydroxo- to oxo-bridged iron(III) molecule-based magnet.

    Science.gov (United States)

    Armentano, Donatella; De Munno, Giovanni; Mastropietro, Teresa F; Julve, Miguel; Lloret, Francesc

    2005-08-10

    Intermolecular proton transfer in solid phase from the hydroxo bridge to a water molecule occurs in a new mu-hydroxo iron(III) compound of formula {EtNH3[Fe2(ox)2Cl2(mu-OH)].2H2O}n leading to a still crystalline compound in which the mu-oxo bridge replaces the mu-hydroxo one. Both three-dimensional compounds exhibit magnetic ordering at Tc ca. 70 K due to a spin canting.

  13. Position-controlled III-V compound semiconductor nanowire solar cells by selective-area metal-organic vapor phase epitaxy.

    Science.gov (United States)

    Fukui, Takashi; Yoshimura, Masatoshi; Nakai, Eiji; Tomioka, Katsuhiro

    2012-01-01

    We demonstrate position-controlled III-V semiconductor nanowires (NWs) by using selective-area metal-organic vapor phase epitaxy and their application to solar cells. Efficiency of 4.23% is achieved for InP core-shell NW solar cells. We form a 'flexible NW array' without a substrate, which has the advantage of saving natural resources over conventional thin film photovoltaic devices. Four junction NW solar cells with over 50% efficiency are proposed and discussed.

  14. The Convergence of Heat, Groundwater & Fracture Permeability. Innovative Play Fairway Modelling Applied to the Tularosa Basin Phase 1 Project Report

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Carlon R. [Ruby Mountain Inc., Salt Lake City, UT (United States); Nash, Gregory D. [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Sorkhabi, Rasoul [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Moore, Joseph [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Simmons, Stuart [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Brandt, Adam [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Barker, Benjamin [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Swanson, Brigitte [Ruby Mountain Inc., Salt Lake City, UT (United States)

    2015-10-16

    This report summarizes the activities and key findings of the project team occurring during Phase 1 (August 2014-October 2015) of the Tularosa Basin Geothermal Play Fairway Analysis Project. The Tularosa Basin Play Fairway Analysis (PFA) project tested two distinct geothermal exploration methodologies covering the entire basin within South Central New Mexico and Far West Texas. Throughout the initial phase of the project, the underexplored basin proved to be a challenging, yet ideal test bed to evaluate effectiveness of the team’s data collection techniques as well as the effectiveness of our innovative PFA. Phase 1 of the effort employed a low-cost, pragmatic approach using two methods to identify potential geothermal plays within the study area and then compared and contrasted the results of each method to rank and evaluate potential plays. Both methods appear to be very effective and highly transferable to other areas.

  15. Exploratory analysis of a phase III trial of pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment

    Directory of Open Access Journals (Sweden)

    Takahashi Hiroki

    2011-10-01

    Full Text Available Abstract Background A phase III trial in Japan showed that pirfenidone is effective for idiopathic pulmonary fibrosis (IPF. To find out which patients specifically benefit from pirfenidone, we analyzed in an exploratory manner the data from the phase III trial. Methods The patients in the phase III trial were stratified by baseline percentage predicted vital capacity (%VC, arterial oxygen partial pressure (PaO2, and the lowest oxygen saturation by pulse oximetry (SpO2 during the 6-minute steady-state exercise test (6MET. In the subpopulations, changes in VC and subjective symptoms (cough and dyspnea on the Fletcher, Hugh-Jones [F, H-J] Classification scale were evaluated in patients treated with high-dose (1800 mg/day pirfenidone, low-dose (1200 mg/day pirfenidone, and placebo at week 52. Results Significant efficacy of pirfenidone in reducing the decline in VC could be seen in a subpopulation having %VC ≥ 70% and SpO2 Conclusions IPF patients having %VC ≥ 70% and SpO2 Trial Registration This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC on September 13th, 2005 (Registration Number: JAPICCTI-050121.

  16. Postoperative opioid sparing with injectable hydroxypropyl-β-cyclodextrin-diclofenac: pooled analysis of data from two Phase III clinical trials

    Science.gov (United States)

    Gan, Tong J; Singla, Neil; Daniels, Stephen E; Hamilton, Douglas A; Lacouture, Peter G; Reyes, Christian RD; Carr, Daniel B

    2017-01-01

    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 for the 0–24 through 0–120 hour time periods (P<0.0001), as well as versus ketorolac for the 0–72 through 0–120 hour time periods (P<0.05). HPβCD-diclofenac significantly reduced opioid consumption versus placebo in subgroups based on baseline pain severity (moderate, severe) and age (<65 years, ≥65 years) from the 0–24 hour period onward. When compared to ketorolac, HPβCD-diclofenac also significantly reduced cumulative opioid consumption among patients with moderate baseline pain (0–72 through 0–120 hours) and opioid dose number among patients ≥65 years old (0–24 through 0

  17. 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.)

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

    Directory of Open Access Journals (Sweden)

    Wall Bradley

    2009-06-01

    exercise in this patient population specifically 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. Clinical Trial Registry A Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer; ACTRN12609000200280

  19. Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

    Science.gov (United States)

    Komatsu, Yoshito; Okita, Kenji; Yuki, Satoshi; Furuhata, Tomohisa; Fukushima, Hiraku; Masuko, Hiroyuki; Kawamoto, Yasuyuki; Isobe, Hiroshi; Miyagishima, Takuto; Sasaki, Kazuaki; Nakamura, Michio; Ohsaki, Yoshinobu; Nakajima, Junta; Tateyama, Miki; Eto, Kazunori; Minami, Shinya; Yokoyama, Ryoji; Iwanaga, Ichiro; Shibuya, Hitoshi; Kudo, Mineo; Oba, Koji; Takahashi, Yasuo

    2015-07-01

    The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

  20. Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from the randomised phase III ORAL Start trial

    Science.gov (United States)

    Strand, Vibeke; Lee, Eun Bong; Fleischmann, Roy; Koncz, Tamas; Zwillich, Samuel H; Gruben, David; Wilkinson, Bethanie; Krishnaswami, Sriram; Wallenstein, Gene

    2016-01-01

    Objectives To compare patient-reported outcomes (PROs) in methotrexate (MTX)-naive patients (defined as no prior treatment or ≤3 doses) receiving tofacitinib versus MTX. Methods In the 24-month, phase III, randomised, controlled, ORAL Start trial (NCT01039688), patients were randomised 2:2:1 to receive tofacitinib 5 mg two times per day (n=373), tofacitinib 10 mg two times per day (n=397) or MTX (n=186). PROs assessed included Patient Global Assessment of disease (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and health-related quality of life (Short Form-36 [SF-36]). Results PROs improved following tofacitinib and MTX treatment: benefits were sustained over 24 months. Patients receiving tofacitinib reported earlier responses which were significantly different between each tofacitinib dose and MTX at month 3 through month 24. At month 6 (primary end point), significant improvements versus MTX were observed in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 5/8 domain scores and FACIT-F with tofacitinib 5 mg two times per day; all PROs, except SF-36 Mental Component Summary Score and Medical Outcomes Survey-Sleep, with tofacitinib 10 mg two times per day. At month 6, the proportion of patients reporting improvements ≥minimum clinically important difference were significant versus MTX with tofacitinib 5 mg two times per day in PtGA and 3/8 SF-36 domains; and with tofacitinib 10 mg two times per day in PtGA, pain, HAQ-DI, SF-36 PCS, 4/8 domains and FACIT-F. Conclusions Patients with rheumatoid arthritis receiving tofacitinib 5 and 10 mg two times per day monotherapy versus MTX reported statistically significant and clinically meaningful improvements in multiple PROs over 24 months; onset of benefit with tofacitinib treatment occurred earlier. Trial registration number NCT01039688.

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

    Directory of Open Access Journals (Sweden)

    Forder Peta M

    2011-04-01

    Full Text Available Abstract Background 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. Methods/Design 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. Discussion 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

  2. A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study.

    Science.gov (United States)

    Grénman, Seija; Wiklund, Tom; Jalkanen, Jyrki; Kuoppala, Tapio; Mäenpää, Johanna; Kuronen, Arja; Leminen, Arto; Puistola, Ulla; Vuolo-Merilä, Päivi; Salmi, Tuula; Vuento, Maarit; Yliskoski, Merja; Itälä, Maija; Helenius, Hans; Joensuu, Heikki; Lehtovirta, Pentti

    2006-09-01

    Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

  3. Synthesis, characterization and stability of Cr(III) and Fe(III) hydroxides.

    Science.gov (United States)

    Papassiopi, N; Vaxevanidou, K; Christou, C; Karagianni, E; Antipas, G S E

    2014-01-15

    Chromium is a common contaminant of soils and aquifers and constitutes a major environmental problem. In nature, chromium usually exists in the form of two oxidation states, trivalent, Cr(III), which is relatively innocuous for biota and for the aquatic environment, and hexavalent, Cr(VI) which is toxic, carcinogenic and very soluble. Accordingly, the majority of wastewater and groundwater treatment technologies, include a stage where Cr(VI) is reduced to Cr(III), in order to remove chromium from the aqueous phase and bind the element in the form of environmentally stable solid compounds. In the absence of iron the final product is typically of the form Cr(OH)3·xH2O whereas in the presence of iron the precipitate is a mixed Fe(1-x)Crx(OH)3 phase. In this study, we report on the synthesis, characterisation and stability of mixed (Fex,Cr1-x)(OH)3 hydroxides as compared to the stability of Cr(OH)3. We established that the plain Cr(III) hydroxide, abiding to the approximate molecular formula Cr(OH)3·3H2O, was crystalline, highly soluble, i.e. unstable, with a tendency to transform into the stable amorphous hydroxide Cr(OH)3(am) phase. Mixed Fe0.75Cr0.25(OH)3 hydroxides were found to be of the ferrihydrite structure, Fe(OH)3, and we correlated their solubility to that of a solid solution formed by plain ferrihydrite and the amorphous Cr(III) hydroxide. Both our experimental results and thermodynamic calculations indicated that mixed Fe(III)-Cr(III) hydroxides are more effective enhancers of groundwater quality, in comparison to the plain amorphous or crystalline Cr(III) hydroxides, the latter found to have a solubility typically higher than 50μg/l (maximum EU permitted Cr level in drinking water), while the amorphous Cr(OH)3(am) phase was within the drinking water threshold in the range 5.7hydroxides studied were of extended stability in the 4.8

  4. Selective determination of gold(III) ion using CuO microsheets as a solid phase adsorbent prior by ICP-OES measurement.

    Science.gov (United States)

    Rahman, Mohammed M; Khan, Sher Bahadar; Marwani, Hadi M; Asiri, Abdullah M; Alamry, Khalid A; Al-Youbi, Abdulrahman O

    2013-01-30

    We have prepared calcined CuO microsheets (MSs) by a wet-chemical process using reducing agents in alkaline medium and characterized by UV/vis., fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (XRD), and field-emission scanning electron microscopy (FESEM) etc. The detailed structural, compositional, and optical characterizations of the MSs were evaluated by XRD pattern, FT-IR, X-ray photoelectron spectroscopy (XPS), and UV-vis spectroscopy, respectively which confirmed that the obtained MSs are well-crystalline CuO and possessed good optical properties. The CuO MSs morphology was investigated by FESEM, which confirmed that the calcined nanomaterials were sheet-shaped and grown in large-quantity. Here, the efficiency of the CuO MS was applied for a selective adsorption of gold(III) ion prior to its detection by inductively coupled plasma-optical emission spectrometry (ICP-OES). The selectivity of CuO MSs towards various metal ions, including Au(III), Cd(II), Co(II), Cr(III), Fe(III), Pd(II), and Zn(II) was analyzed. Based on the adsorption isotherm study, it was confirmed that the selectivity of MSs phase was mostly towards Au(III) ion. The static adsorption capacity for Au(III) was calculated to be 57.0 mg g(-1). From Langmuir adsorption isotherm, it was confirmed that the adsorption process was mainly monolayer-adsorption onto a surface containing a finite number of adsorption sites.

  5. Heat capacity and magnetic phase transition of two-dimensional metal-assembled complex, K[{l_brace}Mn{sup III}(3-MeOsalen){r_brace}{sub 2}Fe{sup III}(China){sub 6}

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Yuji [Research Center for Molecular Thermodynamics, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan)]. E-mail: miyazaki@chem.sci.osaka-u.ac.jp; Wang, Qi [Research Center for Molecular Thermodynamics, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Department of Chemistry, Zhejiang University, Hangzhou 310027 (China); Yu, Qing-sen [Research Center for Molecular Thermodynamics, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Department of Chemistry, Zhejiang University, Hangzhou 310027 (China); Matsumoto, Tetsuya [Research Center for Molecular Thermodynamics, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Miyasaka, Hitoshi [Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Minami-ohsawa 1-1, Hachioji, Tokyo 192-0397 (Japan); Matsumoto, Naohide [Department of Chemistry, Faculty of Science, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Sorai, Michio [Research Center for Molecular Thermodynamics, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan)

    2005-06-15

    Heat capacities of the two-dimensional metal-assembled complex, K[{l_brace}Mn{sup III}(3-MeOsalen){r_brace}{sub 2}Fe{sup III}(China){sub 6}] [3-MeOsalen N,N'-ethylenebis(3-methoxysalicylideneaminato) dianion], were measured at the temperatures from 0.5 to 300 K by adiabatic calorimetry. An antiferromagnetic phase transition was observed at T {sub N} = 8.29 K. Above T {sub N}, a heat capacity tail arising from the short-range-order effect of the spins was found, which is characteristic of two-dimensional magnets. The magnetic enthalpy and entropy were evaluated to be {delta}H = 373 J mol{sup -1} and {delta}S = 31.3 J K{sup -1} mol{sup -1}, respectively. The experimental magnetic entropy is in good agreement with {delta}S = R ln (5 x 5 x 2) (=32.5 J K{sup -1} mol{sup -1}; R being the gas constant), which is expected for the metal complex with two Mn(III) ions in high spin state (spin quantum number S = 2) and one Fe(III) ion in low spin state (S = 1/2). The spin wave analysis suggests that the complex shows three-dimensional antiferromagnetic order below T {sub N}. The heat capacity tail above T {sub N} was decreased by grinding and pressurizing the crystal. This mechanochemical effect would originate in the increase of lattice defects and imperfections in the crystal lattice, leading to decrease of the magnetic heat capacity and hence the magnetic enthalpy and entropy.

  6. SURFACE CHEMKIN-III: A Fortran package for analyzing heterogeneous chemical kinetics at a solid-surface - gas-phase interface

    Energy Technology Data Exchange (ETDEWEB)

    Coltrin, M.E.; Kee, R.J.; Rupley, F.M.; Meeks, E.

    1996-05-01

    This document is the user`s manual for the SURFACE CHEMKIN-III package. Together with CHEMKIN-III, this software facilitates the formation, solution, and interpretation of problems involving elementary heterogeneous and gas-phase chemical kinetics in the presence of a solid surface. The package consists of two major software components: an Interpreter and a Surface Subroutine Library. The Interpreter is a program that reads a symbolic description of a user-specified chemical reaction mechanism. One output from the Interpreter is a data file that forms a link to the Surface Subroutine Library, which is a collection of about seventy modular Fortran subroutines that may be called from a user`s application code to return information on chemical production rates and thermodynamic properties. This version of SURFACE CHEMKIN-III includes many modifications to allow treatment of multi-fluid plasma systems, for example modeling the reactions of highly energetic ionic species with a surface. Optional rate expressions allow reaction rates to depend upon ion energy rather than a single thermodynamic temperature. In addition, subroutines treat temperature as an array, allowing an application code to define a different temperature for each species. This version of SURFACE CHEMKIN-III allows use of real (non-integer) stoichiometric coefficients; the reaction order with respect to species concentrations can also be specified independent of the reaction`s stoichiometric coefficients. Several different reaction mechanisms can be specified in the Interpreter input file through the new construct of multiple materials.

  7. 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.

    Science.gov (United States)

    Narin, Ibrahim; Kars, Ayse; Soylak, Mustafa

    2008-01-31

    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 microg/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.

  8. Influence of the V/III ratio in the gas phase on thin epitaxial AlN layers grown on (0001) sapphire by high temperature hydride vapor phase epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Claudel, A., E-mail: arnaud.claudel@grenoble-inp.org [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Fellmann, V. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Science et Ingénierie des Matériaux et des Procédés, Grenoble INP-CNRS-UJF, BP 75, 38402 Saint Martin d' Hères (France); Gélard, I. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Coudurier, N. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Science et Ingénierie des Matériaux et des Procédés, Grenoble INP-CNRS-UJF, BP 75, 38402 Saint Martin d' Hères (France); Sauvage, D. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Balaji, M. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Science et Ingénierie des Matériaux et des Procédés, Grenoble INP-CNRS-UJF, BP 75, 38402 Saint Martin d' Hères (France); Crystal Growth Center, Anna University, Chennai 600025 (India); and others

    2014-12-31

    Thin (0001) epitaxial aluminum nitride (AlN) layers were grown on c-plane sapphire using high temperature hydride vapor phase epitaxy. The experimental set-up consists of a vertical cold-wall quartz reactor working at low pressure in which the reactions take place on a susceptor heated by induction. The reactants used are ammonia and aluminum chlorides in situ formed via hydrogen chloride reaction with high purity aluminum pellets. As-grown AlN layers have been characterized by scanning electron microscopy, atomic force microscopy, X-ray diffraction, transmission electron microscopy, photoluminescence and Raman spectroscopies. The influence of the V/III ratio in the gas phase, from 1.5 to 15, on growth rate, surface morphology, roughness and crystalline quality is investigated in order to increase the quality of thin epitaxial AlN layers grown at high temperature. Typical growth rates of around 0.45 μm/h were obtained for such thin epitaxial AlN layers. The growth rate was unaffected by the V/III ratio. An optimum for roughness, crystalline quality and optical properties seems to exist at V/III = 7.5. As a matter of fact, for a V/III ratio of 7.5, best root mean square roughness and crystalline quality — measured on 0002 symmetric reflection — as low as 6.9 nm and 898 arcsec were obtained, respectively. - Highlights: • Growth of thin epitaxial AlN layers by high temperature hydride vapor phase epitaxy • Influence of V/III ratio on growth rate, morphology and crystalline quality • The effect of surface morphology on strain state and crystal quality is established.

  9. 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

  10. Polymorphism of Alprazolam (Xanax): a review of its crystalline phases and identification, crystallographic characterization, and crystal structure of a new polymorph (form III).

    Science.gov (United States)

    de Armas, Héctor Novoa; Peeters, Oswald M; Van den Mooter, Guy; Blaton, Norbert

    2007-05-01

    A new polymorphic form of Alprazolam (Xanax), 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo-[4,3-alpha][1,4]benzodiazepine, C(17)H(13)ClN(4), has been investigated by means of X-ray powder diffraction (XRPD), single crystal X-ray diffraction, and differential scanning calorimetry (DSC). This polymorphic form (form III) was obtained during DSC experiments after the exothermic recrystallization of the melt of form I. The crystal unit cell dimensions for form III were determined from diffractometer methods. The monoclinic unit cell found for this polymorph using XRPD after indexing the powder diffractogram was confirmed by the cell parameters obtained from single crystal X-ray diffractometry on a crystal isolated from the DSC pans. The single crystal unit cell parameters are: a = 28.929(9), b = 13.844(8), c = 7.361(3) angstroms, beta = 92.82(3) degrees , V = 2944(2) angstroms(3), Z = 8, space group P2(1) (No.4), Dx = 1.393 Mg/m(3). The structure obtained from single crystal X-ray diffraction was used as initial model for Rietveld refinement on the powder diffraction data of form III. The temperature phase transformations of alprazolam were also studied using high temperature XRPD. A review of the different phases available in the Powder Diffraction File (PDF) database for this drug is described bringing some clarification and corrections.

  11. 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.

  12. Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs

    OpenAIRE

    Takeuchi, Tsutomu; Matsubara, Tsukasa; Urata, Yukitomo; Suematsu, Eiichi; Ohta, Shuji; Honjo, Shigeru; Abe, Tohru; Yamamoto, Ami; Miyasaka, Nobuyuki; ,

    2014-01-01

    Objectives To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs. Methods This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies re...

  13. 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

  14. 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

  15. Synthesis, characterization and stability of Cr(III) and Fe(III) hydroxides

    Energy Technology Data Exchange (ETDEWEB)

    Papassiopi, N.; Vaxevanidou, K.; Christou, C.; Karagianni, E.; Antipas, G.S.E., E-mail: gantipas@metal.ntua.gr

    2014-01-15

    Highlights: • Fe(III)–Cr(III) hydroxides enhance groundwater quality better than pure Cr(III) compounds. • Crystalline Cr(OH){sub 3}·3H{sub 2}O was unstable, with a solubility higher than 50 μg/l. • Amorphous Cr(OH){sub 3}(am) was stable with a solubility lower than 50 μg/l in the range 5.7 < pH < 11. • For mixed Fe{sub 0.75}Cr{sub 0.25}(OH){sub 3}, the stability region was extended to 4.8 < pH < 13.5. -- Abstract: Chromium is a common contaminant of soils and aquifers and constitutes a major environmental problem. In nature, chromium usually exists in the form of two oxidation states, trivalent, Cr(III), which is relatively innocuous for biota and for the aquatic environment, and hexavalent, Cr(VI) which is toxic, carcinogenic and very soluble. Accordingly, the majority of wastewater and groundwater treatment technologies, include a stage where Cr(VI) is reduced to Cr(III), in order to remove chromium from the aqueous phase and bind the element in the form of environmentally stable solid compounds. In the absence of iron the final product is typically of the form Cr(OH){sub 3}·xH{sub 2}O whereas in the presence of iron the precipitate is a mixed Fe{sub (1−x)}Cr{sub x}(OH){sub 3} phase. In this study, we report on the synthesis, characterisation and stability of mixed (Fe{sub x},Cr{sub 1−x})(OH){sub 3} hydroxides as compared to the stability of Cr(OH){sub 3}. We established that the plain Cr(III) hydroxide, abiding to the approximate molecular formula Cr(OH){sub 3}·3H{sub 2}O, was crystalline, highly soluble, i.e. unstable, with a tendency to transform into the stable amorphous hydroxide Cr(OH){sub 3}(am) phase. Mixed Fe{sub 0.75}Cr{sub 0.25}(OH){sub 3} hydroxides were found to be of the ferrihydrite structure, Fe(OH){sub 3}, and we correlated their solubility to that of a solid solution formed by plain ferrihydrite and the amorphous Cr(III) hydroxide. Both our experimental results and thermodynamic calculations indicated that mixed Fe(III)–Cr(III

  16. Groundwater cleanup by in-situ sparging. XIII. Random air channels for sparing of dissolved and nonaqueous phase volatiles

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, D.J.; Clarke, A.N. [Eckenfelder, Inc., Nashville, TN (United States); Kaminski, K.M.; Chang, E.Y. [Martin Luther King Magnet High School, Nashville, TN (United States)

    1997-12-01

    A mathematical model is developed to simulate the sparging of dissolved volatile organic compounds (VOCs) and nonaqueous phase liquid (NAPL) from contaminated aquifers. The sparging air moves through the aquifer in persistent, random channels, to which VOC must move by diffusion/dispersion to be removed. The dependence of the rate of remediation on the various model parameters is investigated and some practical conclusions are reached regarding the operation of air sparging wells for aquifer remediation. VOCs of low water solubility (such as alkanes) and present as NAPL are found to be removed by air sparging much more slowly than VOCs of higher water solubility (such as benzene, toluene, ethylbenzene and xylenes) and present as NAPL, due to the very small maximum concentration gradients which can be maintained around droplets of the former. These small concentration gradients result in very slow rates of NAPL solution.

  17. Groundwater cleanup by in-situ sparging. X. Air channeling model for biosparging of nonaqueous phase liquid

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, D.J.; Norris, R.D.; Clarke, A.N. [Eckenfelder Inc., Nashville, TN (United States)

    1996-06-01

    A column model is developed to simulate the removal and biodegradation of dissolved and nonaqueous phase liquid (NAPL) volatile organic compounds (VOCs) from contaminated aquifers by biosparging. The model assumes that the injected air moves through the aquifer in persistent channels and that NAPL must dissolve and move to these channels by diffusion and dispersion. The dependence of model results on several of the parameters of the model is investigated, and suggestions for optimizing biosparging system operations are made. The removal of NAPL VOCs of quite low solubility (such as alkanes) from smear zones below the water is modeled, and is found to be an extremely slow process. Drawing down the water table to below the smear zone by pumping is suggested as a possible solution.

  18. groundwater contribution to crop water requirement groundwater ...

    African Journals Online (AJOL)

    eobe

    Keywords: Groundwater, water table, capillary rise, soil type, waterleaf, ... GROUNDWATER CONTRIBUTION TO WATERLEAF (TALINUM TRIANGULARE) IN OXISOLS, I. J. ... Nutritionally, ... information to facilitate increased crop production,.

  19. 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.

  20. 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.

  1. Dosing considerations for rufinamide in patients with Lennox-Gastaut syndrome: Phase III trial results and real-world clinical data.

    Science.gov (United States)

    Kothare, Sanjeev; Kluger, Gerhard; Sachdeo, Rajesh; Williams, Betsy; Olhaye, Omar; Perdomo, Carlos; Bibbiani, Francesco

    2017-04-01

    Lennox-Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, rufinamide dosing and titration may differ from the trial setting. Here, rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. Results demonstrated that a rapid titration schedule (7 or 14 days) of rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic-atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study - somnolence, vomiting, and pyrexia - occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of rufinamide in LGS. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. 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

    Full Text Available BACKGROUND: 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]. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: Quality control guidelines when applied in field laboratories ensured the reliability and validity

  3. Phase Coupling in Langmuir Wave Packets: Evidence for Four Wave Interactions in Solar Type III Radio Bursts

    Science.gov (United States)

    Thejappa, G.; MacDowall, R. J.; Bergamo, M.

    2012-01-01

    The four wave interaction process, known as the oscillating two stream instability (OTSI) is considered as one of the mechanisms responsible for stabilizing the electron beams associated with solar type III radio bursts. It has been reported that (1) an intense localized Langmuir wave packet associated with a type III burst contains the spectral characteristics of the OTSI: (a) a resonant peak at the local electron plasma frequency, f(sub pe), (b) a Stokes peak at a frequency slightly lower than f(sub pe), (c) anti-Stokes peak at a frequency slightly higher than f(sub pe), and (d) a low frequency enhancement below a few hundred Hz, (2) the frequencies and wave numbers of these spectral components satisfy the resonance conditions of the OTSI, and (3) the peak intensity of the wave packet is well above the thresholds for the OTSI as well as spatial collapse of envelope solitons. Here, for the first time, applying the trispectral analysis on this wave packet, we show that the tricoherence, which measures the degree of coherent four-wave coupling amongst the observed spectral components exhibits a peak. This provides an additional evidence for the OTSI and related spatial collapse of Langmuir envelope solitons in type III burst sources.

  4. Chitosan film loaded with silver nanoparticles-sorbent for solid phase extraction of Al(III), Cd(II), Cu(II), Co(II), Fe(III), Ni(II), Pb(II) and Zn(II).

    Science.gov (United States)

    Djerahov, Lubomir; Vasileva, Penka; Karadjova, Irina; Kurakalva, Rama Mohan; Aradhi, Keshav Krishna

    2016-08-20

    The present study describes the ecofriendly method for the preparation of chitosan film loaded with silver nanoparticles (CS-AgNPs) and application of this film as efficient sorbent for separation and enrichment of Al(III), Cd(II), Cu(II), Co(II), Fe(III), Ni(II), Pb(II) and Zn(II). The stable CS-AgNPs colloid was prepared by dispersing the AgNPs sol in chitosan solution at appropriate ratio and further used to obtain a cast film with very good stability under storage and good mechanical strength for easy handling in aqueous medium. The incorporation of AgNPs in the structure of CS film and interaction between the polymer matrix and nanoparticles were confirmed by UV-vis and FTIR spectroscopy. The homogeneously embedded AgNPs (average diameter 29nm, TEM analysis) were clearly observed throughout the film by SEM. The CS-AgNPs nanocomposite film shows high sorption activity toward trace metals under optimized chemical conditions. The results suggest that the CS-AgNPs nanocomposite film can be feasibly used as a novel sorbent material for solid-phase extraction of metal pollutants from surface waters.

  5. DEMONSTRATION OF FUEL CELLS TO RECOVER ENERGY FROM LANDFILL GAS - PHASE III. DEMONSTRATION TESTS - PHASE IV. GUIDELINES AND RECOMMENDATIONS- VOLUME 1. TECHNICAL REPORT

    Science.gov (United States)

    The report summarizes the results of a four-phase program to demonstrate that fuel cell energy recovery using a commercial phosphoric acid fuel cell is both environmentally sound and commercially feasible. Phase I, a conceptual design and evaluation study, addressed the technical...

  6. Determination of pharmaceutical compounds in surface- and ground-water samples by solid-phase extraction and high-performance liquid chromatography-electrospray ionization mass spectrometry

    Science.gov (United States)

    Cahill, J.D.; Furlong, E.T.; Burkhardt, M.R.; Kolpin, D.; Anderson, L.G.

    2004-01-01

    Commonly used prescription and over-the-counter pharmaceuticals are possibly present in surface- and ground-water samples at ambient concentrations less than 1 μg/L. In this report, the performance characteristics of a combined solid-phase extraction isolation and high-performance liquid chromatography–electrospray ionization mass spectrometry (HPLC–ESI-MS) analytical procedure for routine determination of the presence and concentration of human-health pharmaceuticals are described. This method was developed and used in a recent national reconnaissance of pharmaceuticals in USA surface waters. The selection of pharmaceuticals evaluated for this method was based on usage estimates, resulting in a method that contains compounds from diverse chemical classes, which presents challenges and compromises when applied as a single routine analysis. The method performed well for the majority of the 22 pharmaceuticals evaluated, with recoveries greater than 60% for 12 pharmaceuticals. The recoveries of angiotensin-converting enzyme inhibitors, a histamine (H2) receptor antagonist, and antihypoglycemic compound classes were less than 50%, but were retained in the method to provide information describing the potential presence of these compounds in environmental samples and to indicate evidence of possible matrix enhancing effects. Long-term recoveries, evaluated from reagent-water fortifications processed over 2 years, were similar to initial method performance. Method detection limits averaged 0.022 μg/L, sufficient for expected ambient concentrations. Compound-dependent matrix effects on HPLC/ESI-MS analysis, including enhancement and suppression of ionization, were observed as a 20–30% increase in measured concentrations for three compounds and greater than 50% increase for two compounds. Changing internal standard and more frequent ESI source maintenance minimized matrix effects. Application of the method in the national survey demonstrates that several

  7. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02.

    Science.gov (United States)

    Lee, Eudocia Q; Kuhn, John; Lamborn, Kathleen R; Abrey, Lauren; DeAngelis, Lisa M; Lieberman, Frank; Robins, H Ian; Chang, Susan M; Yung, W K Alfred; Drappatz, Jan; Mehta, Minesh P; Levin, Victor A; Aldape, Kenneth; Dancey, Janet E; Wright, John J; Prados, Michael D; Cloughesy, Timothy F; Gilbert, Mark R; Wen, Patrick Y

    2012-12-01

    The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor-β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents.

  8. A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: A Hellenic Cooperative Oncology Group study

    Directory of Open Access Journals (Sweden)

    Efstratiou Ioannis

    2011-01-01

    Full Text Available Abstract Background Colon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU plus leucovorin (LV was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11 is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer. Methods The study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (IV, LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A versus LV 200 mg/m2 and 5FU 500 mg/m2 IV bolus (Arm B. In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS at three years. Results The probability of overall survival (OS at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436. Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334. With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms. Conclusions Irinotecan added to weekly bolus 5FU plus LV did not result

  9. High temperature process steam application at the Southern Union Refining Company, Hobbs, New Mexico. Solar energy in the oil patch. Final report, Phase III: operation, maintenance, and performance

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, L.E.; McGuire, D.R.

    1984-05-01

    This final report summarizes the technical reports for Phase III of this project. The third phase included the operation, maintenance, upgrade and performance reporting of a 10,080 square foot Solar Industrial Process Heat System installed at the Famariss Energy Refinery of Southern Union Refining Company near Hobbs, New Mexico. This report contains a description of the upgraded system, and a summary of the overall operation, maintenance and performance of the installed system. The results of the upgrade activities can be seen in the last two months of operational data. Steam production was significantly greater in peak flow and monthly total than at any previous time. Also monthly total cost savings was greatly improved even though natural gas costs remain much lower than originally anticipated.

  10. Measurement of the νe and total 8B solar neutrino fluxes with the Sudbury Neutrino Observatory phase-III data set

    Science.gov (United States)

    Aharmim, B.; Ahmed, S. N.; Amsbaugh, J. F.; Anaya, J. M.; Anthony, A. E.; Banar, J.; Barros, N.; Beier, E. W.; Bellerive, A.; Beltran, B.; Bergevin, M.; Biller, S. D.; Boudjemline, K.; Boulay, M. G.; Bowles, T. J.; Browne, M. C.; Bullard, T. V.; Burritt, T. H.; Cai, B.; Chan, Y. D.; Chauhan, D.; Chen, M.; Cleveland, B. T.; Cox, G. A.; Currat, C. A.; Dai, X.; Deng, H.; Detwiler, J. A.; DiMarco, M.; Doe, P. J.; Doucas, G.; Dragowsky, M. R.; Drouin, P.-L.; Duba, C. A.; Duncan, F. A.; Dunford, M.; Earle, E. D.; Elliott, S. R.; Evans, H. C.; Ewan, G. T.; Farine, J.; Fergani, H.; Fleurot, F.; Ford, R. J.; Formaggio, J. A.; Fowler, M. M.; Gagnon, N.; Germani, J. V.; Goldschmidt, A.; Goon, J. TM.; Graham, K.; Guillian, E.; Habib, S.; Hahn, R. L.; Hallin, A. L.; Hallman, E. D.; Hamian, A. A.; Harper, G. C.; Harvey, P. J.; Hazama, R.; Heeger, K. M.; Heintzelman, W. J.; Heise, J.; Helmer, R. L.; Henning, R.; Hime, A.; Howard, C.; Howe, M. A.; Huang, M.; Jagam, P.; Jamieson, B.; Jelley, N. A.; Keeter, K. J.; Klein, J. R.; Kormos, L. L.; Kos, M.; Krüger, A.; Kraus, C.; Krauss, C. B.; Kutter, T.; Kyba, C. C. M.; Lange, R.; Law, J.; Lawson, I. T.; Lesko, K. T.; Leslie, J. R.; Loach, J. C.; MacLellan, R.; Majerus, S.; Mak, H. B.; Maneira, J.; Martin, R.; McCauley, N.; McDonald, A. B.; McGee, S. R.; Mifflin, C.; Miller, G. G.; Miller, M. L.; Monreal, B.; Monroe, J.; Morissette, B.; Myers, A. W.; Nickel, B. G.; Noble, A. J.; O'Keeffe, H. M.; Oblath, N. S.; Ollerhead, R. W.; Orebi Gann, G. D.; Oser, S. M.; Ott, R. A.; Peeters, S. J. M.; Poon, A. W. P.; Prior, G.; Reitzner, S. D.; Rielage, K.; Robertson, B. C.; Robertson, R. G. H.; Rollin, E.; Schwendener, M. H.; Secrest, J. A.; Seibert, S. R.; Simard, O.; Simpson, J. J.; Skensved, P.; Smith, M. W. E.; Sonley, T. J.; Steiger, T. D.; Stonehill, L. C.; Tešić, G.; Thornewell, P. M.; Tolich, N.; Tsui, T.; Tunnell, C. D.; Van Wechel, T.; Van Berg, R.; VanDevender, B. A.; Virtue, C. J.; Wall, B. L.; Waller, D.; Wan Chan Tseung, H.; Wendland, J.; West, N.; Wilhelmy, J. B.; Wilkerson, J. F.; Wilson, J. R.; Wouters, J. M.; Wright, A.; Yeh, M.; Zhang, F.; Zuber, K.

    2013-01-01

    This paper details the solar neutrino analysis of the 385.17-day phase-III data set acquired by the Sudbury Neutrino Observatory (SNO). An array of 3He proportional counters was installed in the heavy-water target to measure precisely the rate of neutrino-deuteron neutral-current interactions. This technique to determine the total active 8B solar neutrino flux was largely independent of the methods employed in previous phases. The total flux of active neutrinos was measured to be 5.54-0.31+0.33(stat.)-0.34+0.36(syst.)×106 cm-2 s-1, consistent with previous measurements and standard solar models. A global analysis of solar and reactor neutrino mixing parameters yielded the best-fit values of Δm2=7.59-0.21+0.19×10-5eV2 and θ=34.4-1.2+1.3degrees.

  11. 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

  12. 3Q/4Q99 Annual M-Area and Metallurgical Laboratory Hazardous Waste Management Facilities Groundwater Monitoring and Corrective-Action Report - Third and Fourth Quarters 1999 - Volumes I, II, and III

    Energy Technology Data Exchange (ETDEWEB)

    Chase, J.

    2000-04-19

    This report describes the groundwater monitoring and corrective-action program at the M-Area Hazardous Waste Management Facility (HWMF) and the Metallurgical Laboratory (Met Lab) HWMF at the Savannah River Site (SRS) during 1999.

  13. 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.

  14. Examination of the coordination sphere of Al(III) in trifluoromethyl-heteroarylalkenolato complex ions by gas-phase IRMPD spectroscopy and computational modelling.

    Science.gov (United States)

    Brückmann, Lisa; Tyrra, Wieland; Mathur, Sanjay; Berden, Giel; Oomens, Jos; Meijer, Anthony J H M; Schäfer, Mathias

    2012-06-01

    A series of aluminium complex ions with trifluoromethyl-heteroarylalkenolato (TMHA) ligands are studied by gas-phase infrared multiphoton-dissociation (IRMPD) spectroscopy and computational modelling. The selected series of aluminium TMHA complex ions are promising species for the initial study of intrinsic binding characteristics of Al(III) cations in the gas phase as corresponding molecular ions. They are readily available for examination by (+) and (-) electrospray ionization mass spectrometry (ESI-MS) by spraying of [Al(3+)⋅(L(-))(3)] solutions. The complex ions under investigation contain trivalent Al(3+) cations with two chelating anionic enolate ligands, [Al(3+)⋅(L(-))(2)](+), providing insights in the nature of the heteroatom-Al bonds. Additionally, the structure of a deprotonated benzimidazole ligand, L(-,) and an anionic complex ion of Al(III) with two doubly deprotonated benzimidazole ligands, [Al(3+)⋅(L(2-))(2)](-), are examined by (-)ESI-IRMPD spectroscopy. Experimental and computational results are highly consistent and allow a reliable identification of the ion structures. In all complex ions examined the planar TMHA ligands are oriented perpendicular to each other around the metal ion, leading to a tetrahedral coordination sphere in which aluminium interacts with the enolate oxygen and heteroaryl nitrogen atoms available in each of the bidentate ligands.

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

    Directory of Open Access Journals (Sweden)

    Michelle M. Kim

    2016-04-01

    Full Text Available BACKGROUND: 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. SIGNIFICANCE: 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.

  16. Defining the Role of Neoadjuvant Chemotherapy Followed by Surgery in Locally Advanced Cancer Cervix: A Meta-analysis of Phase III Trials.

    Science.gov (United States)

    Osman, Mohammed A

    2016-10-01

    This meta-analysis was performed to compare the outcomes between NACT-S and RT for locally advanced cancer cervix. The primary end points were survival benefits. The data sources for the search included medline, national library of medicine, and the embase search engines. Inclusion criteria included studies published between 2000 and 2012, and FIGO stages IB2 to IVA. Studies had to be properly randomized, prospective, or retrospective and only phase III. Further, the studies had to be with two arms, including one arm for neoadjuvant chemotherapy then-surgery (NACT-S), and the other arm for radiotherapy (RT). Data were collected from 1171 patients enrolled in seven phase III trials. The 5-year PFS (progression-free survival) for NACT-S and RT were 62 and 45.5 %, respectively. The 5-year OS for NACT-S and RT were 66 and 49 %, respectively. NACT-S was associated with better late toxicities compared to RT. NACT-S is a reasonable treatment option for locally advanced cancer cervix. It achieved better results than RT, especially for stages from IB2 to IIB.

  17. Results from phase III clinical trials with radachlorine for photodynamic therapy of pre-cancer and early cancer of cervix

    Directory of Open Access Journals (Sweden)

    E. V. Filonenko

    2015-01-01

    Full Text Available The results of clinical study for efficacy of photodynamic therapy (PDT with radachlorine in patients with pre-cancer and cancer of cervix are represented. The study enrolled 30 patients including 4 patients with cervical erosion, 5 patients with cervical intraepithelial neoplasia II, 13 patients with cervical intraepithelial neoplasia III, 4 patients with carcinoma in situ and 4 patients with cervical cancer stage Ia. Radachlorine was administrated as single 30 minute intravenous injection at dose of 1,0 mg/kg of body weight 3 h before irradiation (wavelength of 662 nm, light dose of 300–350 J/cm2. The results of treatment in 26 (86,7% patients was assessed as complete tumor regression and in 4 (13,3% patients — as partial regression. In cervical erosion, intraepithelial neoplasia II and carcinoma in situ groups total regression was in all cases. In the cervical intraepithelial neoplasia III group total regression after first course of PDT was achieved in 77% of patients, in cervical cancer stage Ia group – in 75% of patients. From 3 to 6 months after first course of treatment all patients with partial tumor regression underwent the second course of PDT with complete regression. There were no side-effects due to radachorine or PDT in the course of treatment and during follow-up. Thus, PDT with Russian photosensitizer radachlorine showed high efficiency for treatment of pre-cancer and cancer of cervix. 

  18. NATO/CCMS PILOT STUDY - EVALUATION OF DEMONSTRATED AND EMERGING TECHNOLOGIES FOR THE TREATMENT OF CONTAMINATED LAND AND GROUNDWATER (PHASE III)

    Science.gov (United States)

    The Council of the North Atlantic Treaty Organization (NATO) established the Committee on the Challenges of Modern Society (CCMS) in 1969. CCMS was charged with developing meaningful programs to share information among countries on environmental and societal issues that complemen...

  19. 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

    2016-01-01

    Purpose 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. Experimental Design 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. Results 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 (P<0.001) and higher levels of baseline methylation correlated with the obtainment of stable disease (P=0.04). Conclusions Azacitidine and CAPOX were well tolerated with high rates of stable disease in CIMP-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. PMID:27542211

  20. Groundwater Waters

    Directory of Open Access Journals (Sweden)

    Ramón Llamas

    1999-10-01

    Full Text Available The groundwaters released through springs constituted a basic element for the survival and progressive development of human beings. Man came to learn how to take better advantage of these waters by digging wells, irrigation channels, and galleries. Nevertheless, these activities do not require cooperation nor the collective agreement of relatively large groups of people, as in the case of creating the necessary structures to take advantage of the resources of surfacewaters. The construction and operation of these structures was a powerful factor in the birth of an urban or civil society – the designated water civilizations. The difference between people taking advantage of groundwater, quasi-individually, and those of surface water, where people work in a group, has continued to the present day. Whereas earlier, this difference did not bring about any special problems, the technological advances of this century, especially theturbine pump, have led to a spectacular increase in the use of roundwater. This advance has significantly contributed to reducing hunger in the world and has provided potable water in developing countries. However, the almost generalized lack of planning and control in the exploitation of these groundwaters reflects that they are little or badly understood by the managers of water policy in almost every country. As such, problems have occurred which have often become exaggerated, giving rise to water-myths. These problems, though, should be addressed if the aim is the sustainable usage of surface water as well as groundwater. To counter any misconceptions and to seek solutions to the problems, distinct plans of action can be highlighted: educating the public; fomenting a system of participative management and decisive support for the communities of users of subterranean waters; integrating a sufficient number of experts in hydrology in the various water management organizations;and assuring transparency of the data on

  1. Dating degassed groundwater with 3H/3He

    NARCIS (Netherlands)

    Visser, A.; Broers, H.P.; Bierkens, M.F.P.

    2007-01-01

    The production of gases in groundwater under contaminated locations by geochemical and biological processes is not uncommon. Degassing of these gases from groundwater and repartitioning of noble gases between water and gas phase distorts groundwater dating by 3H/3He. We observed noble gas concentrat

  2. Dating degassed groundwater with 3H/3He

    NARCIS (Netherlands)

    Visser, A.; Broers, H.P.; Bierkens, M.F.P.

    2007-01-01

    The production of gases in groundwater under contaminated locations by geochemical and biological processes is not uncommon. Degassing of these gases from groundwater and repartitioning of noble gases between water and gas phase distorts groundwater dating by 3H/3He. We observed noble gas

  3. Correct usage, ease of use, and preference of two dry powder inhalers in patients with COPD: analysis of five phase III, randomized trials

    Directory of Open Access Journals (Sweden)

    Riley JH

    2016-08-01

    Full Text Available John H Riley,1 Maggie Tabberer,2 Nathalie Richard,3 Alison Donald,3 Alison Church,3 Stephanie S Harris3 1MDC Global Clinical Development – UK, GlaxoSmithKline, 2Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, Middlesex, UK; 3Respiratory Medicines Development Center, GlaxoSmithKline, Durham, NC, USA Background: Handheld inhalers are used to deliver treatment for COPD. Incorrect usage leads to suboptimal disease control. Complex treatment regimens and use of multiple inhalers may reduce patient compliance. The Anoro Ellipta™ dry powder inhaler (DPI simultaneously delivers umeclidinium bromide (UMEC and vilanterol (VI without coformulation being required.Aim: To assess the correct usage and ease of use of the Ellipta™ DPI administering UMEC/VI and to compare patient preference for Ellipta™ with the HandiHaler® through exploratory analyses of patient and observer questionnaires in five Phase III studies.Methods: Two Phase III, 3-month double-blind, placebo-controlled studies assessed the correct usage of the Ellipta™ DPI at Day 1 and after 6 weeks, and ease of use of the Ellipta™ DPI using a nonvalidated patient questionnaire after 6 weeks or early withdrawal. In three 6-month, blinded double-dummy, active comparator studies (two Phase IIIa and one Phase IIIb, patients completed a COPD device preference questionnaire between the Ellipta™ DPI and the HandiHaler® at Day 168 (Week 24 or early withdrawal.Results: In the 3-month placebo-controlled studies, ≥98% of patients used the Ellipta™ DPI correctly and 99% of patients found the inhaler easy/very easy-to-use and the dose counter easy/very easy to read. Across the two Phase IIIa active comparator studies, patients consistently stated a preference for the Ellipta™ DPI over HandiHaler® regarding the number of steps to use (59% vs 17%, time taken to use (62% vs 14%, and ease of use (63% vs 15% regardless of which inhaler contained active drug. Results were consistent

  4. LIQUID PHASE FISCHER-TROPSCH (III & IV) DEMONSTRATION IN THE LAPORTE ALTERNATIVE FUELS DEVELOPMENT UNIT. Final Topical Report. Volume I/II: Main Report. Task 1: Engineering Modifications (Fischer-Tropsch III & IV Demonstration) and Task 2: AFDU Shakedown, Operations, Deactivation (Shut-Down) and Disposal (Fischer-Tropsch III & IV Demonstration).

    Energy Technology Data Exchange (ETDEWEB)

    Bharat L. Bhatt

    1999-06-01

    Slurry phase Fischer-Tropsch technology was successfully demonstrated in DOE's Alternative Fuels Development Unit (AFDU) at LaPorte, Texas. Earlier work at LaPorte, with iron catalysts in 1992 and 1994, had established proof-of-concept status for the slurry phase process. The third campaign (Fischer-Tropsch III), in 1996, aimed at aggressively extending the operability of the slurry reactor using a proprietary cobalt catalyst. Due to an irreversible plugging of catalyst-wax separation filters as a result of unexpected catalyst fines generation, the operations had to be terminated after seven days on-stream. Following an extensive post-run investigation by the participants, the campaign was successfully completed in March-April 1998, with an improved proprietary cobalt catalyst. These runs were sponsored by the U. S. Department of Energy (DOE), Air Products & Chemicals, Inc., and Shell Synthetic Fuels, Inc. (SSFI). A productivity of approximately 140 grams (gm) of hydrocarbons (HC)/ hour (hr)-liter (lit) of expanded slurry volume was achieved at reasonable system stability during the second trial (Fischer-Tropsch IV). The productivity ranged from 110-140 at various conditions during the 18 days of operations. The catalyst/wax filters performed well throughout the demonstration, producing a clean wax product. For the most part, only one of the four filter housings was needed for catalyst/wax filtration. The filter flux appeared to exceed the design flux. A combination of use of a stronger catalyst and some innovative filtration techniques were responsible for this success. There was no sign of catalyst particle attrition and very little erosion of the slurry pump was observed, in contrast to the Fischer-Tropsch III operations. The reactor operated hydrodynamically stable with uniform temperature profile and gas hold-ups. Nuclear density and differential pressure measurements indicated somewhat higher than expected gas hold-up (45 - 50 vol%) during Fischer

  5. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    Science.gov (United States)

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  6. Phase I/II Clinical Study of Tosedostat, an Inhibitor of Aminopeptidases, in Patients With Acute Myeloid Leukemia and Myelodysplasia

    NARCIS (Netherlands)

    Lowenberg, Bob; Morgan, Gareth; Ossenkoppele, Gert J.; Burnett, Alan K.; Zachee, Pierre; Duehrsen, Ulrich; Dierickx, Daan; Mueller-Tidow, Carsten; Sonneveld, Pieter; Krug, Utz; Bone, Elisabeth; Flores, Nicolas; Richardson, Alison F.; Hooftman, Leon; Jenkins, Chris; Zweegman, Sonja; Davies, Faith

    2010-01-01

    Purpose To identify the maximum-tolerated dose (MTD) and to evaluate the antileukemic activity of tosedostat (formerly CHR-2797), an orally bioavailable aminopeptidase inhibitor. Patients and Methods In phase I, the MTD of once daily oral doses of tosedostat in hematologic malignancies was defined.

  7. Groundwater and security

    NARCIS (Netherlands)

    Conti, K.I.; Kukurić, N.; Gupta, J.; Pahl-Wostl, C.; Bhaduri, A.; Gupta, J.

    2016-01-01

    Humans abstract two hundred times more groundwater than oil, annually. Ironically, the role of groundwater in water management and supply is underappreciated, partially due to its invisibility. By conducting a literature survey and investigating groundwater information databases, this chapter answer

  8. Cytokine Profile of Children Hospitalized with Virologically-Confirmed Dengue during Two Phase III Vaccine Efficacy Trials.

    Directory of Open Access Journals (Sweden)

    Anke Harenberg

    2016-07-01

    Full Text Available Two large-scale efficacy studies with the recombinant yellow fever-17D-dengue virus, live-attenuated, tetravalent dengue vaccine (CYD-TDV candidate undertaken in Asia (NCT01373281 and Latin America (NCT01374516 demonstrated significant protection against dengue disease during two years' active surveillance (active phase. Long-term follow up of participants for breakthrough disease leading to hospitalization is currently ongoing (hospital phase.We assessed the cytokine profile in acute sera from selected participants hospitalized (including during the active phase up to the beginning of the second year of long-term follow up for both studies. The serum concentrations of 38 cytokines were measured in duplicate using the Milliplex Human Cytokine MAGNETIC BEAD Premixed 38 Plex commercial kit (Millipore, Billerica, MA, USA. Partial least squares discriminant analyses did not reveal any difference in the overall cytokine profile of CYD-TDV and placebo recipients hospitalized for breakthrough dengue regardless of stratification used. In addition, there was no difference in the cytokine profile for breakthrough dengue among those aged <9 years versus those aged ≥ 9 years.These exploratory findings show that CYD-TDV does not induce a particular immune profile versus placebo, corroborating the clinical profile observed.

  9. TLC-MS versus TLC-LC-MS fingerprints of herbal extracts. Part III. Application of the reversed-phase liquid chromatography systems with C18 stationary phase.

    Science.gov (United States)

    Sajewicz, Mieczysław; Staszek, Dorota; Natic, Maja; Waksmundzka-Hajnos, Monika; Kowalska, Teresa

    2011-08-01

    In the previous paper from this series, we proposed mass spectrometric fingerprinting of complex botanical samples upon the examples of the pharmacologically important phenolic acids and flavonoids selectively extracted from Salvia lavandulifolia. In this study, we explore fingerprinting efficiency with a novel two-dimensional analytical system composed of the reversed-phase thin-layer chromatography and the reversed-phase high performance liquid chromatography with mass spectrometric detection (2D RP-TLC-RP-LC-MS). We also compare its efficiency with that of the one-dimensional analytical system (the reversed-phase thin-layer chromatography with mass spectrometric detection; 1D RP-TLC-MS). As our present study is basically focused on the method development, we considered it as justified to carry out our comparison with the phenolic acid extracts selectively derived from the Salvia lavandulifolia species, similar as it was done in Part II from this series. Upon the results obtained, it was established that the 1D RP-TLC-MS mode and the 2D RP-TLC-RP-LC-MS mode can be applied to fingerprinting of herbal extracts, and that the 2D RP-TLC-RP-LC mode can provide a more abundant information than that originating from the 1D RP-TLC mode.

  10. 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.

  11. Variability in the Propagation Phase of CFD-Based Noise Prediction: Summary of Results From Category 8 of the BANC-III Workshop

    Science.gov (United States)

    Lopes, Leonard; Redonnet, Stephane; Imamura, Taro; Ikeda, Tomoaki; Zawodny, Nikolas; Cunha, Guilherme

    2015-01-01

    The usage of Computational Fluid Dynamics (CFD) in noise prediction typically has been a two part process: accurately predicting the flow conditions in the near-field and then propagating the noise from the near-field to the observer. Due to the increase in computing power and the cost benefit when weighed against wind tunnel testing, the usage of CFD to estimate the local flow field of complex geometrical structures has become more routine. Recently, the Benchmark problems in Airframe Noise Computation (BANC) workshops have provided a community focus on accurately simulating the local flow field near the body with various CFD approaches. However, to date, little effort has been given into assessing the impact of the propagation phase of noise prediction. This paper includes results from the BANC-III workshop which explores variability in the propagation phase of CFD-based noise prediction. This includes two test cases: an analytical solution of a quadrupole source near a sphere and a computational solution around a nose landing gear. Agreement between three codes was very good for the analytic test case, but CFD-based noise predictions indicate that the propagation phase can introduce 3dB or more of variability in noise predictions.

  12. 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

  13. Proposal of a concept and design of a randomized phase III trial investigating the survival effect of para-aortic lymphadenectomy in endometrial cancer.

    Science.gov (United States)

    Watari, Hidemichi; Todo, Yukiharu; Kang, Sokbom; Odagiri, Tetsuji; Sakuragi, Noriaki

    2014-02-01

    Although prospective studies have failed to show the therapeutic effect of lymphadenectomy in the surgical treatment of endometrial cancer, several retrospective studies including the SEPAL study revealed the survival effect of lymphadenectomy. To prospectively investigate the survival benefit of para-aortic lymphadenectomy shown in the SEPAL study, we are proposing a new concept of a randomized phase III trial. An appropriate study population will be selected according to the preoperative assessments (evaluation of myometrial invasion and cervical invasion with magnetic resonance imaging, extrauterine spread with computed tomography, and histological type and grade by pathological evaluation) to estimate the risk of lymph node metastasis. Patients relevant to potential International Federation of Gynecology and Obstetrics (2008) stage IB, II and III diseases will be eligible, and randomly assigned to two arms: pelvic lymphadenectomy alone (control), or pelvic and para-aortic lymphadenectomy (experimental). After initial surgery, patients with postoperative pathological risk factors for recurrence will receive adjuvant chemotherapy. Because we aim to investigate the therapeutic significance of primary treatments, including surgery and adjuvant chemotherapy, the primary end-point could be recurrence-free survival. One of the most important issues to successfully perform this prospective study is to assure the quality of lymphadenectomy (extent and area), which could be evaluated based on the number of harvested nodes and objective evaluation of dissected area by videos and/or photos. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  14. 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 low-dose lenalidomide and alemtuzumab induced major perturbations of T cells, including increased proliferative activity and cytotoxic potential.

  15. Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-centre trial of the RTS,S/AS01 malaria vaccine in African children

    Directory of Open Access Journals (Sweden)

    Lievens Marc

    2011-08-01

    Full Text Available Abstract Background There has been much debate about the appropriate statistical methodology for the evaluation of malaria field studies and the challenges in interpreting data arising from these trials. Methods The present paper describes, for a pivotal phase III efficacy of the RTS, S/AS01 malaria vaccine, the methods of the statistical analysis and the rationale for their selection. The methods used to estimate efficacy of the primary course of vaccination, and of a booster dose, in preventing clinical episodes of uncomplicated and severe malaria, and to determine the duration of protection, are described. The interpretation of various measures of efficacy in terms of the potential public health impact of the vaccine is discussed. Conclusions The methodology selected to analyse the clinical trial must be scientifically sound, acceptable to regulatory authorities and meaningful to those responsible for malaria control and public health policy. Trial registration Clinicaltrials.gov NCT00866619

  16. Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

    Directory of Open Access Journals (Sweden)

    Van Nguyen Thu

    2011-09-01

    Full Text Available Abstract Background Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. Materials and Methods We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA Results Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51. Maximal grade 1, 2, and 3 acute ( Conclusions Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.

  17. Progress and Continuing Challenges in GaSb-based III-V Alloys and Heterostructures Grown by Organometallic Vapor Phase Epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    CA Wang

    2004-05-06

    This paper discusses progress in the preparation of mid-IR GaSb-based III-V materials grown by organometallic vapor phase epitaxy (OMVPE). The growth of these materials is complex, and fundamental and practical issues associated with their growth are outlined. Approaches that have been explored to further improve the properties and performance are briefly reviewed. Recent materials and device results on GaInAsSb bulk layers and GaInAsSb/AlGaAsSb heterostructures, grown lattice matched to GaSb, are presented. State-of-the-art GaInAsSb materials and thermophotovoltaic devices have been achieved. This progress establishes the high potential of OMVPE for mid-IR GaSb-based devices.

  18. An instrument for in situ coherent x-ray studies of metal-organic vapor phase epitaxy of III-nitrides

    Science.gov (United States)

    Ju, Guangxu; Highland, Matthew J.; Yanguas-Gil, Angel; Thompson, Carol; Eastman, Jeffrey A.; Zhou, Hua; Brennan, Sean M.; Stephenson, G. Brian; Fuoss, Paul H.

    2017-03-01

    We describe an instrument that exploits the ongoing revolution in synchrotron sources, optics, and detectors to enable in situ studies of metal-organic vapor phase epitaxy (MOVPE) growth of III-nitride materials using coherent x-ray methods. The system includes high-resolution positioning of the sample and detector including full rotations, an x-ray transparent chamber wall for incident and diffracted beam access over a wide angular range, and minimal thermal sample motion, giving the sub-micron positional stability and reproducibility needed for coherent x-ray studies. The instrument enables surface x-ray photon correlation spectroscopy, microbeam diffraction, and coherent diffraction imaging of atomic-scale surface and film structure and dynamics during growth, to provide fundamental understanding of MOVPE processes.

  19. 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.

  20. Fluorouracil Based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy Following Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the US Intergroup/RTOG 9704 Phase III Trial

    Science.gov (United States)

    Regine, William F.; Winter, K.A.; Abrams, R.; Safran, H.; Hoffman, J.P.; Konski, A.; Benson, A.B.; Macdonald, J.S.; Rich, T.A.; Willett, C.G.

    2011-01-01

    Background The impact of the addition of gemcitabine (G) to 5-FU chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. Methods Following resection of pancreatic adenocarcinoma patients were randomized to pre and post CRT 5-FU vs. pre and post CRT G. 5-FU = continuous (CI) at 250 mg/m2/day. G = 1000 mg/m2 weekly; both given over 3 weeks pre and 12 weeks post - CRT. CRT = 50.4 Gy with CI 5-FU. Primary endpoint was survival for all patients and for pancreatic head tumor patients. Results Four hundred and fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n=388) had a median survival and 5-year OS of 20.5 months and 22% with G vs. 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the G arm with pancreatic head tumors experienced a trend towards improved OS (p=0.08). First site of relapse local recurrence in 28% of patients vs. distant relapse in 73%. Conclusion(s) The sequencing of 5-FU CRT with G as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥ 70% of patients. These findings serve as the basis for the recently activated EORTC/US Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of G. PMID:21499862

  1. 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

  2. Efficacy and Safety of Risedronate in Osteoporosis Subjects with Comorbid Diabetes, Hypertension, and/or Dyslipidemia: A Post Hoc Analysis of Phase III Trials Conducted in Japan.

    Science.gov (United States)

    Inoue, Daisuke; Muraoka, Ryoichi; Okazaki, Ryo; Nishizawa, Yoshiki; Sugimoto, Toshitsugu

    2016-02-01

    Many osteoporotics have comorbid diabetes mellitus (DM), hypertension (HT), and dyslipidemia (DL). However, whether such comorbidities alter response to anti-osteoporotic treatment is unknown. We did post hoc analyses of combined data from three risedronate Japanese phase III trials to determine whether the presence of DM, HT, or DL affects its efficacy and safety. Data from 885 subjects who received 48-week treatment with risedronate were collected and combined from the three phase III trials. They were divided into two groups by the presence or absence of comorbidities: DM (n = 53) versus non-DM (n = 832); HT (n = 278) versus non-HT (n = 607); and DL (n = 292) versus non-DL (n = 593). Bone mineral density (BMD), urinary type 1 collagen N-telopeptide (uNTX), and serum bone-specific alkaline phosphatase (BAP) were measured at baseline and sequentially until 48 weeks. BMD or bone markers were not different between any of the two groups. Overall, BMD was increased by 5.52%, and uNTX and BAP were decreased by 35.4 and 33.8%, respectively. Some bone markers were slightly lower in DM and DL subjects, but the responses to risedronate were not significantly different. Statin users had lower uNTX and BAP, but showed no difference in the treatment response. All the other medications had no apparent effect. Adverse event incidence was marginally higher in DL compared with non-DL (Relative risk 1.06; 95% confidence interval 1.01-1.11), but was not related to increase in any specific events. Risedronate shows consistent safety and efficacy in suppressing bone turnover and increasing BMD in osteoporosis patients with comorbid DM, HT, and/or DL.

  3. Radioimmunotherapy in medullary thyroid cancer using bispecific antibody and iodine 131-labeled bivalent hapten: preliminary results of a phase I/II clinical trial.

    Science.gov (United States)

    Kraeber-Bodéré, F; Bardet, S; Hoefnagel, C A; Vieira, M R; Vuillez, J P; Murat, A; Ferreira, T C; Bardiès, M; Ferrer, L; Resche, I; Gautherot, E; Rouvier, E; Barbet, J; Chatal, J F

    1999-10-01

    The toxicity and therapeutic efficacy of escalating doses of anti-carcinoembryonic antigen x anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid)-In bispecific monoclonal antibody (F6-734) and iodine 131-labeled bivalent hapten were determined in a Phase I/II trial. A total of 26 patients with recurrences of medullary thyroid cancer documented by imaging and a rise in serum thyrocalcitonin were enrolled. Twenty to 50 mg of F6-734 and 40-100 mCi of 131I-hapten were injected 4 days apart. Quantitative scintigraphy was performed after the second injection for dosimetry estimations in eight cases. Clinical, biological, and morphological follow-up was carried out for 1 year after treatment. The mean percentage of injected activity per gram of tumor at the time of maximum uptake was 0.08% (range, 0.003-0.26%). The tumor biological half-life ranged from 3 to 95 days, and tumor doses ranged from 2.91 to 184 cGy/mCi. The estimated tumor-to-nontumor dose ratios were 43.8 x 53.4, 29.6 x 35.3, 10.9 x 13.6, and 8.4 x 10.0 for total body, red marrow, liver, and kidney, respectively. Grade III/IV hematological toxicity was observed in seven patients, most of them with bone metastases. Among the 17 evaluable patients, 4 pain reliefs, 5 minor tumor responses, and 4 biological responses with decrease of thyrocalcitonin were observed. Nine patients developed human anti-mouse antibody. Dose-limiting toxicity was hematological, and maximum tolerated activity was 48 mCi/m2 in this group of patients, most of whom had suspected bone marrow involvement. The therapeutic responses observed in patients mainly with a small tumor burden are encouraging for the performance of a Phase II trial with minimal residual disease.

  4. A Phase III Skin Cancer Chemoprevention Study of DFMO: Long-term Follow-up of Skin Cancer Events and Toxicity

    Science.gov (United States)

    Kreul, Sarah M.; Havighurst, Tom; Kim, KyungMann; Mendonça, Eneida A.; Wood, Gary S.; Snow, Stephen; Borich, Abbey; Verma, Ajit; Bailey, Howard H.

    2012-01-01

    Decreasing the incidence of non-melanoma skin cancer (NMSC) is of great importance in regards to future healthcare services. Given the previously reported preventive effects of α-difluoromethylornithine (DFMO) in skin and colon cancer trials, we determined appropriate cause to update the clinical data on the subjects from the recently reported Randomized, Double-Blind, Placebo-Controlled Phase III Skin Cancer Prevention Study of DFMO. Our intention was to retrospectively assess the further incidence of skin cancer, other malignancies, and adverse events of patients accrued to our phase III skin cancer prevention study of DFMO. Clinical records of 209 UW Health subjects were reviewed, and 2092.7 person years of on study (884.3 person years) and post study (1208.4 person years) follow-up for these patients were assessed for new NMSC events and recurrence rates from the on study period, the post study period, and the two study periods combined. No evidence of increased significant diagnoses or serious adverse events was observed in the DFMO participants. The initially observed, marginally significant reduction (p=0.069) in NMSC rates for DFMO subjects relative to placebo continued without evidence of rebound. Event rates after discontinuation from study for total NMSCs (DFMO 0.236 NMSC/person/year, placebo 0.297, p=0.48) or the subtypes of BCCs (DFMO 0.179 BCC/person/year, placebo 0.190, p=0.77) and SCCs (DFMO 0.057 SCC/person/year, placebo 0.107, p=0.43) are listed. Follow-up data revealed a persistent but insignificant reduction in new NMSCs occurring in DFMO subjects without evidence of latent or cumulative toxicity relative to placebo subjects. PMID:23060038

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

    Science.gov (United States)

    Petersen, Lone K; Restrepo, Jaime; Moreira, Edson D; Iversen, Ole-Erik; Pitisuttithum, Punnee; Van Damme, Pierre; Joura, Elmar A; Olsson, Sven-Erik; Ferris, Daron; Block, Stan; Giuliano, Anna R; Bosch, Xavier; Pils, Sophie; Cuzick, Jack; Garland, Suzanne M; Huh, Warner; Kjaer, Susanne K; Bautista, Oliver M; Hyatt, Donna; Maansson, Roger; Moeller, Erin; Qi, Hong; Roberts, Christine; Luxembourg, Alain

    2017-06-01

    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. 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. GMTs to all 9 vaccine HPV types decreased with age at vaccination initiation, and were otherwise generally similar among the demographic subgroups defined by gender, race and region of residence. For all subgroups defined by race or region of residence, GMTs were higher in girls and boys than in young women. Vaccination of subjects who were seropositive at day 1 to a vaccine HPV type resulted in higher GMTs to that type, compared with those in subjects who were seronegative for that type at day 1. 9vHPV vaccine immunogenicity was robust among subjects with differing baseline characteristics. It was generally comparable across subjects of different races and from different regions. Greater immunogenicity in girls and boys versus young women (the population used to establish 9vHPV vaccine efficacy in clinical studies) indicates that the anti-HPV responses generated by the vaccine in adolescents from all races or regions were sufficient to induce high-level protective efficacy. This immunogenicity profile supports a widespread 9vHPV vaccination program and early vaccination. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Solutions Remediate Contaminated Groundwater

    Science.gov (United States)

    2010-01-01

    During the Apollo Program, NASA workers used chlorinated solvents to clean rocket engine components at launch sites. These solvents, known as dense non-aqueous phase liquids, had contaminated launch facilities to the point of near-irreparability. Dr. Jacqueline Quinn and Dr. Kathleen Brooks Loftin of Kennedy Space Center partnered with researchers from the University of Central Florida's chemistry and engineering programs to develop technology capable of remediating the area without great cost or further environmental damage. They called the new invention Emulsified Zero-Valent Iron (EZVI). The groundwater remediation compound is cleaning up polluted areas all around the world and is, to date, NASA's most licensed technology.

  7. 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).

  8. A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors.

    Science.gov (United States)

    Kristeleit, Rebecca; Shapiro, Geoffrey I; Burris, Howard A; Oza, Amit M; LoRusso, Patricia; Patel, Manish R; Domchek, Susan M; Balmaña, Judith; Drew, Yvette; Chen, Lee-May; Safra, Tamar; Montes, Ana; Giordano, Heidi; Maloney, Lara; Goble, Sandra; Isaacson, Jeff; Xiao, Jim; Borrow, Jen; Rolfe, Lindsey; Shapira-Frommer, Ronnie

    2017-08-01

    Purpose: Rucaparib is a potent, oral, small-molecule PARP inhibitor. This phase I-II study was the first to evaluate single-agent oral rucaparib at multiple doses.Experimental Design: Part 1 (phase I) sought to determine the MTD, recommended phase II dose (RP2D), and pharmacokinetics of oral rucaparib administered in 21-day continuous cycles in patients with advanced solid tumors. Part 2A (phase II) enrolled patients with platinum-sensitive, high-grade ovarian carcinoma (HGOC) associated with a germline BRCA1/2 mutation who received two to four prior regimens and had a progression-free interval of 6 months or more following their most recent platinum therapy. The primary endpoint was investigator-assessed objective response rate (ORR) by RECIST version 1.1.Results: In part 1, 56 patients received oral rucaparib (40 to 500 mg once daily and 240 to 840 mg twice daily). No MTD was identified per protocol-defined criteria; 600 mg twice daily was selected as the RP2D based on manageable toxicity and clinical activity. Pharmacokinetics were approximately dose-proportional across all dose levels. In part 2A, 42 patients with germline BRCA1/2-mutated HGOC received rucaparib 600 mg twice daily. Investigator-assessed ORR was 59.5%. The most common treatment-emergent adverse events (all grades) were asthenia/fatigue (85.7%; 36/42), nausea (83.3%; 35/42), anemia (71.4%; 30/42), alanine transaminase and/or aspartate transaminase elevations (57.1%; 24/42), and vomiting (54.8%; 23/42). Among 98 patients, 5 (5.1%) discontinued because of an adverse event (excluding disease progression).Conclusions: Rucaparib was tolerable and had activity in patients with platinum-sensitive germline BRCA1/2-mutated HGOC. Clin Cancer Res; 23(15); 4095-106. ©2017 AACR. ©2017 American Association for Cancer Research.

  9. Exoplanet Imaging with a Phase-induced Amplitude Apodization Coronagraph III. Hybrid Approach: Optical Design and Diffraction Analysis

    CERN Document Server

    Pluzhnik, E A; Galicher, R; Guyon, O; Martinache, F; Ridgway, S T; Woodruff, R A

    2005-01-01

    Properly apodized pupils can deliver point spread functions (PSFs) free of Airy rings, and are suitable for high dynamical range imaging of extrasolar terrestrial planets (ETPs). To reach this goal, classical pupil apodization (CPA) unfortunately requires most of the light gathered by the telescope to be absorbed, resulting in poor throughput and low angular resolution. Phase-induced amplitude apodization (PIAA) of the telescope pupil (Guyon 2003) combines the advantages of classical pupil apodization (particularly low sensitivity to low order aberrations) with full throughput, no loss of angular resolution and little chromaticity, which makes it, theoretically, an extremely attractive coronagraph for direct imaging of ETPs. The two most challenging aspects of this technique are (1) the difficulty to polish the required optics shapes and (2) diffraction propagation effects which, because of their chromaticity, can decrease the spectral bandwidth of the coronagraph. We show that a properly designed hybrid syst...

  10. 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.

  11. Geohydrology of Big Bear Valley, California: phase 1--geologic framework, recharge, and preliminary assessment of the source and age of groundwater

    Science.gov (United States)

    Flint, Lorraine E.; Contributions by Brandt, Justin; Christensen, Allen H.; Flint, Alan L.; Hevesi, Joseph A.; Jachens, Robert; Kulongoski, Justin T.; Martin, Peter; Sneed, Michelle

    2012-01-01

    The Big Bear Valley, located in the San Bernardino Mountains of southern California, has increased in population in recent years. Most of the water supply for the area is pumped from the alluvial deposits that form the Big Bear Valley groundwater basin. This study was conducted to better understand the thickness and structure of the groundwater basin in order to estimate the quantity and distribution of natural recharge to Big Bear Valley. A gravity survey was used to estimate the thickness of the alluvial deposits that form the Big Bear Valley groundwater basin. This determined that the alluvial deposits reach a maximum thickness of 1,500 to 2,000 feet beneath the center of Big Bear Lake and the area between Big Bear and Baldwin Lakes, and decrease to less than 500 feet thick beneath the eastern end of Big Bear Lake. Interferometric Synthetic Aperture Radar (InSAR) was used to measure pumping-induced land subsidence and to locate structures, such as faults, that could affect groundwater movement. The measurements indicated small amounts of land deformation (uplift and subsidence) in the area between Big Bear Lake and Baldwin Lake, the area near the city of Big Bear Lake, and the area near Sugarloaf, California. Both the gravity and InSAR measurements indicated the possible presence of subsurface faults in subbasins between Big Bear and Baldwin Lakes, but additional data are required for confirmation. The distribution and quantity of groundwater recharge in the area were evaluated by using a regional water-balance model (Basin Characterization Model, or BCM) and a daily rainfall-runoff model (INFILv3). The BCM calculated spatially distributed potential recharge in the study area of approximately 12,700 acre-feet per year (acre-ft/yr) of potential in-place recharge and 30,800 acre-ft/yr of potential runoff. Using the assumption that only 10 percent of the runoff becomes recharge, this approach indicated there is approximately 15,800 acre-ft/yr of total recharge in

  12. THE RESULTS OF A PHASE III COMPARATIVE CLINICAL TRIAL OF RITUXIMAB (ACELLBIA® AND MABTHERA® IN RHEUMATOID ARTHRITIS (THE BIORA STUDY

    Directory of Open Access Journals (Sweden)

    E. L. Nasonov

    2016-01-01

    Full Text Available The article considers the results of an international multicenter randomized clinical trial of the efficacy and safety of the brand-name drug rituximab (MabThera, a monoclonal antibody against CD20 antigen of B cells, and its biosimi-lar drug (Acellbia® (the BIORA study in patients with rheumatoid arthritis (RA refractory to therapy with tumor necrosis factor-а inhibitors.Objective: to provide evidence for the therapeutic equivalence of Acellbia® and MabThera® and also to assess their interchangeability.Subjects and methods. The trial enrolled adult patients with active seropositive RA, who were randomized into two groups (1:1: 1 the patients who received Acellbia® 1000 mg intravenously on days 1 and 15; 2 those who had MabThera® in a similar way. When RA activity persisted at 24 weeks, there was re-randomization (1:1 with a partial overlap: Group 1 patients were randomized into group AA (the drug of the second therapy cycle was Acellbia® or Group AM (that was MabThera®, the similar methodology was followed in Group 2 (Groups MM and MA. Throughout the study, the patients received methotrexate at a stable dose of 7.5—25 mg/week and folic acid at a dose of 5 mg/week. The follow-up lasted 48 weeks.Results and discussion. 24 weeks after treatment initiation, the ACR20 response was observed in 84.1% of the patients in the Acellbia® group (95% CI, 74.75—90.50 and in 87% in the MabThera® group (95% CI, 77.71—92.79%; p = 0.773, which suggests that the drugs are therapeutically equivalent. In the second phase of the study, the efficiency of therapy remained high; there were no differences in Groups AA/MM, AA/AM and MM/MA. In both phases, the safety profile of the drugs was comparable; the immunogenicity of treatment remained low. The findings suggest that the brand-name MabThera® and its biosimilar drug Acellbia® are equivalent. Switching from the biosimilar drug to the brand-name one and vice versa has no negative impact on treatment

  13. Elastic Anomalies Accompanying Phase Transitions in (CaSr)TiO3 Perovskite III: Experimental Investigation of Polycrystalline Samples

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter,M.; Li, B.; Liebermann, R.

    2007-01-01

    Bulk and shear moduli of polycrystalline samples of perovskites with different compositions across the CaTiO3-SrTiO3 solid solution have been measured at ambient conditions and in-situ at high pressures by pulse-echo ultrasonic methods. The samples were prepared as dense pellets by hot pressing synthetic powders at {approx}7.5 GPa and {approx}1000 C. Any variations of bulk modulus due to phase transitions are small, but significant anomalies have been observed in the shear modulus at ambient conditions. These are associated with a sequence of symmetry changes PmFormulam -> I4/mcm -> Pbcm -> Pnma with increasing CaTiO3 content. Comparison with variations in elastic properties predicted using Landau theory suggests that a substantial part of the elastic softening observed in tetragonal samples could be due to anelastic contributions from transformation twin walls. This additional softening does not occur in orthorhombic samples, and the transition from tetragonal to orthorhombic symmetry results in a stiffening of the shear modulus. No overt evidence was found for a phase transition I4/mcm {leftrightarrow} Pnma at high pressures in Ca0.35Sr0.65TiO3 but small changes in the trends of both bulk and shear moduli in the range 2.5-3 GPa could be due either to a different transition or a change in compression mechanism. A PmFormulam {leftrightarrow} I4/mcm transition at {approx}2 GPa in Ca0.05Sr0.95TiO3 shows the same form of softening as observed for the transition as a function of composition. A simple model of twin wall contributions to the compliance of tetragonal samples failed to match the observed variations that, alternatively, seem to follow {Delta}G {proportional_to} q4 where {Delta}G is the change in shear modulus and q4 the driving order parameter for the PmFormulam {leftrightarrow} I4/mcm transition. Analogous elastic behavior is expected to occur in (Mg,Fe)SiO3 and CaSiO3 perovskites at high pressures and temperatures.

  14. 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.

  15. Double-Blind Phase III Randomized Trial of the Antiprogestin Agent Mifepristone in the Treatment of Unresectable Meningioma: SWOG S9005.

    Science.gov (United States)

    Ji, Yongli; Rankin, Cathryn; Grunberg, Steven; Sherrod, Andy E; Ahmadi, Jamshid; Townsend, Jeannette J; Feun, Lynn G; Fredericks, Ruth K; Russell, Christy A; Kabbinavar, Fairooz F; Stelzer, Keith J; Schott, Anne; Verschraegen, Claire

    2015-12-01

    Progesterone receptors are expressed in approximately 70% of meningiomas. Mifepristone is an oral antiprogestational agent reported to have modest activity in a phase II study. This multicenter, prospective, randomized, placebo-controlled phase III trial conducted by SWOG was planned to define the role of mifepristone in the treatment of unresectable meningioma. Eligible patients were randomly assigned to receive either mifepristone or placebo for 2 years unless disease progressed. Patients who were stable or responding to protocol therapy after 2 years had the option to continue with the same blinded therapy. Serial follow-up allowed assessment of efficacy and toxicity. Time to treatment failure and overall survival were ascertained for all randomly assigned patients. On progression, patients receiving placebo could cross over and receive active drug. Among 164 eligible patients, 80 were randomly assigned to mifepristone and 84 to placebo. Twenty-four patients (30%) were able to complete 2 years of mifepristone without disease progression, adverse effects, or other reasons for discontinuation. Twenty-eight patients (33%) in the placebo arm completed the 2-year study. There was no statistical difference between the arms in terms of failure-free or overall survival. Long-term administration of mifepristone was well tolerated but had no impact on patients with unresectable meningioma. © 2015 by American Society of Clinical Oncology.

  16. Phase I/II Trial of 5-Fluorouracil and a Noncytotoxic Dose Level of Suramin in Patients with Metastatic Renal Cell Carcinoma

    Science.gov (United States)

    George, Saby; Dreicer, Robert; Au, Jessie J. L.; Shen, Tong; Rini, Brian I.; Roman, Susan; Cooney, Matthew M.; Mekhail, Tarek; Elson, Paul; Wientjes, Guillaume M.; Ganapathi, Ram; Bukowski, Ronald M.

    2010-01-01

    Background Renal cell carcinoma (RCC) is recognized as a neoplasm resistant to chemotherapy. In vitro experiments demonstrated that suramin, at noncytotoxic doses, enhanced the activity of chemotherapy including 5-fluorouracil (5-FU) in xenograft models. Patients and Methods A phase I/II trial of noncytotoxic suramin in combination with weekly 5-FU in patients with metastatic RCC was conducted. The treatment consisted of intravenous (I.V.) suramin followed by a 500 mg/m2 I.V. bolus of 5-FU given 4.5 hours after starting suramin. In the phase I portion, a cohort of 6 patients received a suramin dose calculated to achieve a plasma level of 10–50 μmol/L. Therapy was administered once weekly for 6 doses, followed by 2 weeks off. This was followed by a phase II portion in which the primary goal was to determine the objective response rate. Results Twenty-three patients were enrolled in the study: 6 in the phase I portion and 17 in phase II. Seventy-eight percent of patients were men, the mean age was 58.8 years, 96% had previous nephrectomy, and 70% had received previous systemic therapy. Histologic subtype was clear cell in 91%. Dose-limiting toxicity was observed in 1 of 6 patients (grade 3 hypersensitivity related to suramin infusion). The suramin dosing nomogram used in phase I and II portions of the trial yielded the desired plasma level of 10–50 μmol/L from 4.5 hours to 48 hours after infusion in 94 of 115 treatments. No objective responses were noted, and the median time to treatment failure was 2.5 months. The major toxicities (all grades) were fatigue (83%), nausea/vomiting (78%), diarrhea (61%), and chills (61%). Conclusion Suramin levels expected to reverse fibroblast growth factor–induced resistance can be achieved with the dosing regimen used in this study. The toxicity observed with suramin and 5-FU was acceptable. The combination does not have clinical activity in patients with metastatic RCC. PMID:18824429

  17. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study

    Directory of Open Access Journals (Sweden)

    Moehler Markus

    2011-08-01

    Full Text Available Abstract Background Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neoadjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC has been designed to explore the efficacy of neoadjuvant chemotherapy. Methods/Design This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2 for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2 followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked

  18. Arsenic(III) and arsenic(V) speciation during transformation of lepidocrocite to magnetite.

    Science.gov (United States)

    Wang, Yuheng; Morin, Guillaume; Ona-Nguema, Georges; Brown, Gordon E

    2014-12-16

    Bioreduction of As(V) and As-bearing iron oxides is considered to be one of the key processes leading to arsenic pollution in groundwaters in South and Southeast Asia. Recent laboratory studies with simple aqueous media showed that secondary Fe(II)-bearing phases (e.g., magnetite and green rust), which commonly precipitate during bioreduction of iron oxides, captured arsenic species. The aim of the present study was to follow arsenic speciation during the abiotic Fe(II)-induced transformation of As(III)- and As(V)-doped lepidocrocite to magnetite, and to evaluate the influence of arsenic on the transformation kinetics and pathway. We found green rust formation is an intermediate phase in the transformation. Both As(III) and As(V) slowed the transformation, with the effect being greater for As(III) than for As(V). Prior to the formation of magnetite, As(III) adsorbed on both lepidocrocite and green rust, whereas As(V) associated exclusively with green rust, When magnetite precipitated, As(III) formed surface complexes on magnetite nanoparticles and As(V) is thought to have been incorporated into the magnetite structure. These processes dramatically lowered the availability of As in the anoxic systems studied. These results provide insights into the behavior of arsenic during magnetite precipitation in reducing environments. We also found that As(V) removal from solution was higher than As(III) removal following magnetite formation, which suggests that conversion of As(III) to As(V) is preferred when using As-magnetite precipitation to treat As-contaminated groundwaters.

  19. Evaluation of Groundwater Impacts to Support the National Environmental Policy Act Environmental Assessment for the INL Remote-Handled Low-Level Waste Disposal Project

    Energy Technology Data Exchange (ETDEWEB)

    Annette Schafer, Arthur S. Rood, A. Jeffrey Sondrup

    2011-12-23

    Groundwater impacts have been analyzed for the proposed remote-handled low-level waste disposal facility. The analysis was prepared to support the National Environmental Policy Act environmental assessment for the top two ranked sites for the proposed disposal facility. A four-phase screening and analysis approach was documented and applied. Phase I screening was site independent and applied a radionuclide half-life cut-off of 1 year. Phase II screening applied the National Council on Radiation Protection analysis approach and was site independent. Phase III screening used a simplified transport model and site-specific geologic and hydrologic parameters. Phase III neglected the infiltration-reducing engineered cover, the sorption influence of the vault system, dispersion in the vadose zone, vertical dispersion in the aquifer, and the release of radionuclides from specific waste forms. These conservatisms were relaxed in the Phase IV analysis which used a different model with more realistic parameters and assumptions. Phase I screening eliminated 143 of the 246 radionuclides in the inventory from further consideration because each had a half-life less than 1 year. An additional 13 were removed because there was no ingestion dose coefficient available. Of the 90 radionuclides carried forward from Phase I, 57 radionuclides had simulated Phase II screening doses exceeding 0.4 mrem/year. Phase III and IV screening compared the maximum predicted radionuclide concentration in the aquifer to maximum contaminant levels. Of the 57 radionuclides carried forward from Phase II, six radionuclides were identified in Phase III as having simulated future aquifer concentrations exceeding maximum contaminant limits. An additional seven radionuclides had simulated Phase III groundwater concentrations exceeding 1/100th of their respective maximum contaminant levels and were also retained for Phase IV analysis. The Phase IV analysis predicted that none of the thirteen remaining

  20. Idaho Water Rental Pilot Project Probability/Coordination Study Resident Fish and Wildlife Impacts Phase III, 1996 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Leitzinger, Eric J. [Idaho Dept. of Fish and Game, Boise, ID (United States)

    1997-12-01

    Phase 3 began in 1995 with the overall goal of quantifying changes in resident fish habitat in the Snake River Basin upstream of Brownlee Reservoir resulting from the release of salmon flow augmentation water. Existing data, in the form of weighted usable area versus flow relationships, were used to estimate habitat changes for white sturgeon (Acipenser transinontanus) and rainbow trout (Oncorhynchus mykiss) in the Snake River between C.J. Strike Dam and Brownlee pool. The increased flows resulted in increased habitat for adult and juvenile white sturgeon and adult rainbow trout. But, the flows have failed to meet mean monthly flow recommendations for the past three years despite the addition of the flow augmentation releases. It is unlikely that the flow augmentation releases have had any significant long-term benefit for sturgeon and rainbow trout in the Snake River. Flow augmentation releases from the Boise and Payette rivers have in some years helped to meet or exceed minimum flow recommendations in these tributaries. The minimum flows would not have been reached without the flow augmentation releases. But, in some instances, the timing of the releases need to be adjusted in order to maximize benefits to resident fishes in the Boise and Payette rivers.

  1. Three-Dimensional Groundwater Models of the 300 Area at the Hanford Site, Washington State

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Mark D.; Rockhold, Mark L.; Thorne, Paul D.; Chen, Yousu

    2008-09-01

    Researchers at Pacific Northwest National Laboratory developed field-scale groundwater flow and transport simulations of the 300 Area to support the 300-FF-5 Operable Unit Phase III Feasibility Study. The 300 Area is located in the southeast portion of the U.S. Department of Energy’s Hanford Site in Washington State. Historical operations involving uranium fuel fabrication and research activities at the 300 Area have contaminated engineered liquid-waste disposal facilities, the underlying vadose zone, and the uppermost aquifer with uranium. The main objectives of this research were to develop numerical groundwater flow and transport models to help refine the site conceptual model, and to assist assessment of proposed alternative remediation technologies focused on the 300 Area uranium plume.

  2. Phase I and II feasibility study report for the 300-FF-5 operable unit

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    The purpose of this Phase I/II feasibility study is to assemble and screen a list of alternatives for remediation of the 300-FF-5 operable site on the Hanford Reservation. This screening is based on information gathered in the Phase I Remedial Investigation (RI) and on currently available information on remediation technologies. The alternatives remaining after screening provide a range of response actions for remediation. In addition, key data needs are identified for collection during a Phase II RI (if necessary). This Phase I/II FS represents a primary document as defined by the Tri-Party Agreement, but will be followed by a Phase III FS that will further develop the alternatives and provide a detailed evaluation of them. The following remedial action objectives were identified for the 300-FF-5 operable unit: Limit current human exposure to contaminated groundwater in the unit; Limit discharge of contaminated groundwater to the Columbia River; Reduce contaminant concentrations in groundwater below acceptable levels by the year 2018.

  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. Characterisation of organic matter associated with groundwater arsenic in reducing aquifers of southwestern Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Al Lawati, Wafa M. [School of Earth, Atmospheric and Environmental Sciences, Williamson Research Centre for Molecular Environmental Science, University of Manchester, Manchester (United Kingdom); Higher College of Technology, Ministry of Manpower, Muscat (Oman); Jean, Jiin-Shuh [Department of Earth Sciences, National Cheng Kung University, 1 University Road, Tainan 701, Taiwan (China); Kulp, Thomas R. [Department of Earth Sciences and Environmental Studies, State University of New York, Binghamton, NY (United States); Lee, Ming-Kuo [Department of Geology and Geography, Auburn University, Auburn, AL (United States); Polya, David A. [School of Earth, Atmospheric and Environmental Sciences, Williamson Research Centre for Molecular Environmental Science, University of Manchester, Manchester (United Kingdom); Liu, Chia-Chuan [Department of Earth Sciences, National Cheng Kung University, 1 University Road, Tainan 701, Taiwan (China); Dongen, Bart E. van, E-mail: Bart.vanDongen@manchester.ac.uk [School of Earth, Atmospheric and Environmental Sciences, Williamson Research Centre for Molecular Environmental Science, University of Manchester, Manchester (United Kingdom)

    2013-11-15

    Highlights: ► First lipid analysis of Taiwanese aquifer sediments from groundwater As-prone region. ► Both plant-derived terrestrial and mature hydrocarbon lipid sources identified. ► Organic matter sources similar to those of other high As groundwater aquifers. ► Groundwater arsenic at depth controlled by biotic As mobilisation processes. ► Biotic As mobilisation not controlled by a specific source of analysed organic matter. -- Abstract: Arsenic (As) in groundwaters extensively used by people across the world constitutes a serious public health threat. The importance of organic matter (OM) as an electron donor in microbially-mediated reduction of As(V) or Fe(III)-bearing As-host minerals leading to mobilisation of solid-phase arsenic is widely recognised. Notwithstanding this, there are few studies characterising OM in such aquifers and, in particular, there is a dearth of data from the classic arsenic bearing aquifers in southwestern Taiwan. Organic geochemical analyses of sediments from a known groundwater arsenic hot-spot in southwestern Taiwan revealed contributions of thermally mature and plant derived origin, consistent with OM sources in all other Asian groundwater aquifer sediments analysed to date, indicating comparable sources and routes of OM transfer. The combined results of amended As(V) reduction assays with the organic geochemical analysis revealed that the microbiological process of dissimilatory As(V) reduction is active in this aquifer, but it is not controlled by a specific source of analysed OM. These indicate that (i) part of the OM that was considered to be less bio-available could still be used as an electron donor or (ii) other electron donors, not analysed in present study, could be controlling the rate of As release.

  5. 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

    Directory of Open Access Journals (Sweden)

    Vekemans Johan

    2011-08-01

    Full Text Available Abstract Background 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. Methods 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

  6. 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

  7. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study

    Science.gov (United States)

    Canaud, Bernard; Mingardi, Giulio; Braun, Johann; Aljama, Pedro; Kerr, Peter G.; Locatelli, Francesco; Villa, Giuseppe; Van Vlem, Bruno; McMahon, Alan W.; Kerloëguen, Cécile; Beyer, Ulrich

    2008-01-01

    Background. Extending the administration interval of erythropoiesis-stimulating agents (ESAs) represents an opportunity to improve the efficiency of anaemia management in patients with chronic kidney disease (CKD). However, effective haemoglobin (Hb) maintenance can be challenging with epoetin alfa and epoetin beta administered at extended intervals. C.E.R.A., a continuous erythropoietin receptor activator, has a unique pharmacologic profile and long half-life (∼130 h), allowing administration at extended intervals. Phase III results have demonstrated that C.E.R.A. administered once every 4 weeks effectively maintains stable Hb levels in patients with CKD on dialysis. Methods. STRIATA (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. Treatment for Anaemia) was a multicentre, open-label randomized phase III study to evaluate the efficacy and safety of intravenous C.E.R.A. administered once every 2 weeks (Q2W) for Hb maintenance following direct conversion from darbepoetin alfa (DA). Adult patients on dialysis receiving stable intravenous DA once weekly (QW) or Q2W were randomized (1:1) to continue their current DA regimen (n = 156) or receive intravenous C.E.R.A. Q2W (n = 157) for 52 weeks. Doses were adjusted to maintain Hb levels within ± 1.0 g/dl of baseline and between 10.0 and 13.5 g/dl. The primary endpoint was the mean Hb change between baseline and the evaluation period (weeks 29–36). Results. Most patients (>80%) received DA QW before randomization. The mean (95% CI) difference between C.E.R.A. and DA in the primary endpoint was 0.18 g/dl (−0.05, 0.41), within a pre-defined non-inferiority limit. C.E.R.A. was clinically non-inferior to DA (P < 0.0001) in maintaining Hb levels. Both treatments were well tolerated. Conclusions. Stable Hb levels were successfully maintained in patients on haemodialysis directly converted to Q2W intravenous C.E.R.A. from DA. PMID:18586762

  8. 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

    Directory of Open Access Journals (Sweden)

    Combs Stephanie E

    2010-11-01

    Full Text Available Background 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. Methods/Design 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. Discussion Up

  9. 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

  10. 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

  11. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

    NARCIS (Netherlands)

    Stupp, R.; Hegi, M.E.; Mason, W.P.; Bent, M.J. van den; Taphoorn, M.J.B.; Janzer, R.C.; Ludwin, S.K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; Brandes, A.A.; Gijtenbeek, J.M.M.; Marosi, C.; Vecht, C.J.; Mokhtari, K.; Wesseling, P.; Villa, S.; Eisenhauer, E.; Gorlia, T.; Weller, M.; Lacombe, D.; Cairncross, J.G.; Mirimanoff, R.O.

    2009-01-01

    BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and ad

  12. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study : 5-year analysis of the EORTC-NCIC trial

    NARCIS (Netherlands)

    Stupp, Roger; Hegi, Monika E.; Mason, Warren P.; van den Bent, Martin J.; Taphoorn, Martin J. B.; Janzer, Robert C.; Ludwin, Samuel K.; Allgeier, Anouk; Fisher, Barbara; Belanger, Karl; Hau, Peter; Brandes, Alba A.; Gijtenbeek, Johanna; Marosi, Christine; Vecht, Charles J.; Mokhtari, Karima; Wesseling, Pieter; Villa, Salvador; Eisenhauer, Elizabeth; Gorlia, Thierry; Weller, Michael; Lacombe, Denis; Cairncross, J. Gregory; Mirimanoff, Rene-Olivier

    2009-01-01

    Background In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adj

  13. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage II and IV low-grade malignant non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    A. Hagenbeek; H. Eghbali; S. Monfardini; U. Viloto; P.J. Hoskin; C. de Wolf-Peeters; K. MacLennan; E. Staab-Renner; J. Kalmus; A. Schott; I. Teodorovic; A. Negrouk; M. van Glabbeke; R. Marcus

    2006-01-01

    Purpose To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study. Patients and Methods Between 1993 and 1997

  14. Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: Results of a multicenter, single-blind, interindividual, randomized clinical phase III trial

    NARCIS (Netherlands)

    B. Tombach (Bernd); K. Bohndorf (Klaus); W. Brodtrager (Wolfgang); C.D. Claussen (Claus); C. Düber (Christoph); M. Galanski (Michael); E. Grabbe (Eckhardt); G. Gortenuti (Giacomo); M. Kuhn (Michael); W. Gross-Fengels (Walter); R. Hammerstingl (Renate); B. Happel (Brigitte); G. Heinz-Peer (Gertraud); G. Jung (Gregor); T. Kittner (Thomas); R. Lagalla; P. Lengsfeld (Philipp); R. Loose (Reinhard); R.H.G. Oyen (Raymond); P. Pavlica (Pietro); C. Pering (Christiane); R. Pozzi Mucelli (Roberto Silvio); T. Persigehl (Thorsten); P. Reimer (Peter); N.S. Renken (Nomdo); G.M. Richter (Götz); E.J. Rummeny (Ernst); F. Schäfer (Fritz); M. Szczerbo-Trojanowska (Malgorzata); A. Urbanik (Andrzej); T.J. Vogl (Thomas); P. Hajek (Paul)

    2008-01-01

    textabstractThe purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, in

  15. QUALITY ASSURANCE OF 4D-CT SCAN TECHNIQUES IN MULTICENTER PHASE III TRIAL OF SURGERY VERSUS STEREOTACTIC RADIOTHERAPY (RADIOSURGERY OR SURGERY FOR OPERABLE EARLY STAGE (STAGE 1A) NON-SMALL-CELL LUNG CANCER [ROSEL] STUDY)

    NARCIS (Netherlands)

    Hurkmans, Coen W.; van Lieshout, Maarten; Schuring, Danny; van Heumen, Marielle J. T.; Cuijpers, Johan P.; Lagerwaard, Frank J.; Widder, Joachim; van der Heide, Uulke A.; Senan, Suresh

    2011-01-01

    Purpose: To determine the accuracy of four-dimensional computed tomography (4D-CT) scanning techniques in institutions participating in a Phase III trial of surgery vs. stereotactic radiotherapy (SBRT) for lung cancer. Methods and Materials: All 9 centers performed a 4D-CT scan of a motion phantom (

  16. Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer : updated survival analysis of the AVAPERL (MO22089) randomized phase III trial

    NARCIS (Netherlands)

    Barlesi, F.; Scherpereel, A.; Gorbunova, V.; Gervais, R.; Vikstrom, A.; Chouaid, C.; Chella, A.; Kim, J. H.; Ahn, M. J.; Reck, M.; Pazzola, A.; Kim, H. T.; Aerts, J. G.; Morando, C.; Loundou, A.; Groen, H. J. M.; Rittmeyer, A.

    The randomized, phase III AVAPERL trial evaluated the safety and efficacy of bevacizumab maintenance with or without pemetrexed in nonsquamous nonsmall-cell lung cancer (nsNSCLC). Progression-free survival (PFS) was significantly prolonged with bevacizumab-pemetrexed, but overall survival (OS) data

  17. 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

  18. 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.

  19. EORTC QLQ-COMU26: a questionnaire for the assessment of communication between patients and professionals. Phase III of the module development in ten countries.

    Science.gov (United States)

    Arraras, Juan Ignacio; Wintner, Lisa M; Sztankay, Monika; Tomaszewski, Krzysztof A; Hofmeister, Dirk; Costantini, Anna; Bredart, Anne; Young, Teresa; Kuljanic, Karin; Tomaszewska, Iwona M; Kontogianni, Meropi; Chie, Wei-Chu; Kulis, Dagmara; Greimel, Eva

    2017-05-01

    Communication between patients and professionals is one major aspect of the support offered to cancer patients. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) has developed a cancer-specific instrument for the measurement of different issues related to the communication between cancer patients and their health care professionals. Questionnaire development followed the EORTC QLG Module Development Guidelines. A provisional questionnaire was pre-tested (phase III) in a multicenter study within ten countries from five cultural areas (Northern and South Europe, UK, Poland and Taiwan). Patients from seven subgroups (before, during and after treatment, for localized and advanced disease each, plus palliative patients) were recruited. Structured interviews were conducted. Qualitative and quantitative analyses have been performed. One hundred forty patients were interviewed. Nine items were deleted and one shortened. Patients' comments had a key role in item selection. No item was deleted due to just quantitative criteria. Consistency was observed in patients' answers across cultural areas. The revised version of the module EORTC QLQ-COMU26 has 26 items, organized in 6 scales and 4 individual items. The EORTC COMU26 questionnaire can be used in daily clinical practice and research, in various patient groups from different cultures. The next step will be an international field test with a large heterogeneous group of cancer patients.

  20. Bortezomib-thalidomide-based regimens improved clinical outcomes without increasing toxicity as induction treatment for untreated multiple myeloma: a meta-analysis of phase III randomized controlled trials.

    Science.gov (United States)

    Huang, Hejing; Zhou, Lili; Peng, Lihui; Fu, Weijun; Zhang, Chunyang; Hou, Jian

    2014-09-01

    Novel agents thalidomide and bortezomib have significantly improved myeloma treatment. However, it remains unclear whether patients will benefit more from the combination therapy of these two agents. Our meta-analysis aims to compare the efficiency, and more importantly, the safety of bortezomib-thalidomide-based (VT-based) versus bortezomib-based or thalidomide-based (V-based/T-based) regimens as induction therapy in patients with previously untreated myeloma. Overall, five phase III RCTs including 1765 patients were identified. Compared with V-based or T-based regimens, VT-based regimens significantly improved CR (OR=2.22, 95% CI [1.44, 3.43]), ORR (OR=2.19, 95% CI [1.51, 3.19]) as well as PFS (HR=0.69, 95% CI [0.54, 0.88]), but not OS (HR=1.04, 95% CI [0.91, 1.19]). Notably, most expected side effects of bortezomib or thalidomide were comparable in both groups, including hematologic (anemia, neutropenia, thrombocytopenia), nonhematologic (peripheral neuropathy, deep venous thrombosis, infections, gastrointestinal events) side effects and discontinuation during or after induction therapy. These results suggest that combination of thalidomide and bortezomib might be a better first-line choice for patients with untreated myeloma.

  1. Outpatient bendamustine and idarubicin for upfront therapy of elderly acute myeloid leukaemia/myelodysplastic syndrome: a phase I/II study using an innovative statistical design.

    Science.gov (United States)

    Lionberger, Jack M; Pagel, John M; Sandhu, Vicky K; Xie, Hu; Shadman, Mazyar; Mawad, Raya; Boehm, Alexandra; Dean, Carol; Shannon-Dorcy, Kathleen; Scott, Bart L; Deeg, Hans Joachim; Becker, Pamela S; Hendrie, Paul C; Walter, Roland B; Ostronoff, Fabiana; Appelbaum, Frederick R; Estey, Elihu H

    2014-08-01

    Combinations of agents may improve outcomes among elderly acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS) patients. We performed an adaptive phase I/II trial for newly-diagnosed AML or high-risk MDS patients aged ≥50 years using a Bayesian approach to determine whether 1 of 3 doses of bendamustine (45, 60, 75 mg/m(2) days 1-3), together with idarubicin (12 mg/m(2) days 1-2), might provide a complete response (CR) rate ≥40% with 10% marrow blasts; median age 73 years). None of the three bendamustine doses in combination with idarubicin met the required CR and toxicity rates; the 75 mg/m(2) dose because of excess toxicity (two of three patients) and the 60 mg/m(2) dose because of low efficacy (CR rate 10/33), although no grade 3-4 non-haematological toxicity was seen at this dose. Median survival was 7·2 months. All patients began treatment as outpatients but hospitalization was required in 90% (35/39). Although we did not find a dose of bendamustine combined with idarubicin that would provide a CR rate of >40% with acceptable toxicity, bendamustine may have activity in AML/MDS patients, suggesting its addition to other regimens may be warranted.

  2. Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study

    Directory of Open Access Journals (Sweden)

    Freihorst Joachim

    2007-08-01

    Full Text Available Abstract Background Vaccination against Pseudomonas aeruginosa is a desirable albeit challenging strategy for prevention of airway infection in patients with cystic fibrosis. We assessed the immunogenicity of a nasal vaccine based on the outer membrane proteins F and I from Pseudomonas aeruginosa in the lower airways in a phase I/II clinical trial. Methods N = 12 healthy volunteers received 2 nasal vaccinations with an OprF-OprI gel as a primary and a systemic (n = 6 or a nasal booster vaccination (n = 6. Antibodies were assessed in induced sputum (IS, bronchoalveolar lavage (BAL, and in serum. Results OprF-OprI-specific IgG and IgA antibodies were found in both BAL and IS at comparable rates, but differed in the predominant isotype. IgA antibodies in IS did not correlate to the respective serum levels. Pulmonary antibodies were detectable in all vaccinees even 1 year after the vaccination. The systemic booster group had higher IgG levels in serum. However, the nasal booster group had the better long-term response with bronchial antibodies of both isotypes. Conclusion The nasal OprF-OprI-vaccine induces a lasting antibody response at both, systemic and airway mucosal site. IS is a feasible method to non-invasively assess bronchial antibodies. A further optimization of the vaccination schedule is warranted.

  3. 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.

  4. Lymphadenectomy in locally advanced cervical cancer study (LiLACS): Phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA cervical cancer.

    Science.gov (United States)

    Frumovitz, Michael; Querleu, Denis; Gil-Moreno, Antonio; Morice, Philippe; Jhingran, Anuja; Munsell, Mark F; Macapinlac, Homer A; Leblanc, Eric; Martinez, Alejandra; Ramirez, Pedro T

    2014-01-01

    Radiation treatment planning for women with locally advanced cervical cancer (stages IB2-IVA) is often based on positron emission tomography (PET). PET, however, has poor sensitivity in detecting metastases in aortocaval nodes. We have initiated a study with the objective of determining whether pre-therapeutic laparoscopic surgical staging followed by tailored chemoradiation improves survival as compared with PET/computed tomography (CT) radiologic staging alone followed by chemoradiation. This international, multicenter phase III trial will enroll 600 women with stages IB2-IVA cervical cancer and PET/CT findings showing fluorodeoxyglucose-avid pelvic nodes and fluorodeoxyglucose-negative para-aortic nodes. Eligible patients will be randomized to undergo either pelvic radiotherapy with chemotherapy (standard-of-care arm) or surgical staging via a minimally invasive extraperitoneal approach followed by tailored radiotherapy with chemotherapy (experimental arm). The primary end point is overall survival. Secondary end points are disease-free survival, short- and long-term morbidity with pre-therapeutic surgical staging, and determination of anatomic locations of metastatic para-aortic nodes in relationship to the inferior mesenteric artery. We believe this study will show that tailored chemoradiation after pre-therapeutic surgical staging improves survival as compared with chemoradiation based on PET/CT in women with stages IB2-IVA cervical cancer.

  5. Telomerase-pulsed dendritic cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Schmiedel, Alexandra

    2006-02-01

    Full Text Available Objective: Therapeutic vaccination with dendritic cells (DC showed promising results in first clinical trials in cases of metastatic renal cell carcinoma (RCC. Human telomerase reverse transcriptase (hTERT could be a potential target because it is detectable in more than 85% of human tumors including RCC. Design: 10 patients with progressive metastatic RCC were enrolled in a clinical phase I/II trial using DC pulsed with hTERT-peptide. Beside toxicity and feasibility aspects, a complex immune monitoring including in vitro data were evaluated. In addition to detection of tumor-specific effector cells we investigated their functionality like IFN-γ secretion and cytotoxic activity against tumor cells. Results: The vaccine was well tolerated. Two patients showed a mixed response (MR and one patient a stable disease (SD. Interestingly, responders showed cytotoxic activity already before start of therapy and there was a significant increase in cytotoxic activity of effector cells from all responders (SD and MR patients after the first vaccination. In contrast non-responders showed no cytotoxic activity before and during treatment. Therefore, cytotoxic activity might be used as a predictive marker in the future. Tetramer staining detected higher amounts of tumor-specific cytotoxic cells in responding patients compared to non-responders. Also, responders possessed increasing amounts of IFN-γ producing immunological effector cells. Conclusion: Telomerase-pulsed DC could enhance a tumor-specific immune response against RCC.

  6. 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.

  7. Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

    Directory of Open Access Journals (Sweden)

    Maria Graziella Catalano

    2016-01-01

    Full Text Available Anaplastic thyroid cancer (ATC has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly and valproic acid (1,000 mg/day; the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11.

  8. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Roberto Hegg

    Full Text Available OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI for the rate of neutropenia between the two groups (12.61% was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa’s approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯.

  9. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Science.gov (United States)

    Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

    2016-01-01

    OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

  10. Prevalence and risk factors of asthma and allergic diseases in primary schoolchildren living in Bushehr, Iran: phase I, III ISAAC protocol.

    Directory of Open Access Journals (Sweden)

    Shokrollah Farrokhi

    2014-10-01

    Full Text Available Asthma and allergic diseases present a major health burden. Information on the prevalence of these diseases indicates that these diseases are increasing in various parts of the world. It was hoped that this study would be helpful to health system policy-makers in planning allergy prevention programs in the region.The prevalence of asthma and allergic diseases and relation between the various risk factors involved were assessed among schoolchildren in the city of Bushehr, Iran. The ISAAC Phase I and III questionnaires were completed by parents of 1280 children aged 6-7 years and self-completed by 1115 students aged 13-14 years.The prevalence of atopic eczema, allergic rhinitis and asthma among 6-7 year-old students were 12.1%, 11.8% and 6.7%, respectively. While, the prevalence of these diseases among 13-14 year-old students were found to be 19%, 30% and 7.6%, respectively. There was an association between asthma and allergic rhinitis as well as eczema (p<0.05. Consumption of fast food as a risk factor was significantly associated with asthma (p=0.03.The prevalence of asthma and allergic diseases was high among schoolchildren in the city of Bushehr, Iran. Also an association was observed between the fast food consumption and asthma.

  11. 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.

  12. Innovative applications of energy storage in a restructured electricity marketplace : Phase III final report : a study for the DOE Energy Storage Systems Program.

    Energy Technology Data Exchange (ETDEWEB)

    Eyer, James M. (Distributed Utility Associates, Livermore, CA); Erdman, Bill (Distributed Utility Associates, Livermore, CA); Iannucci, Joseph J., Jr. (, . Distributed Utility Associates, Livermore, CA)

    2005-03-01

    This report describes Phase III of a project entitled Innovative Applications of Energy Storage in a Restructured Electricity Marketplace. For this study, the authors assumed that it is feasible to operate an energy storage plant simultaneously for two primary applications: (1) energy arbitrage, i.e., buy-low-sell-high, and (2) to reduce peak loads in utility ''hot spots'' such that the utility can defer their need to upgrade transmission and distribution (T&D) equipment. The benefits from the arbitrage plus T&D deferral applications were estimated for five cases based on the specific requirements of two large utilities operating in the Eastern U.S. A number of parameters were estimated for the storage plant ratings required to serve the combined application: power output (capacity) and energy discharge duration (energy storage). In addition to estimating the various financial expenditures and the value of electricity that could be realized in the marketplace, technical characteristics required for grid-connected distributed energy storage used for capacity deferral were also explored.

  13. Evaluation of clinical utility of {sup 123}I-MIBG scintigraphy in localization of tumors of sympathetic and adrenomedullary origin. A report of multicenter phase III clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Katsumi; Horiike, Shigeharu [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine; Kubo, Atsushi; Kusakabe, Kiyoko; Murata, Hajime; Masaki, Hidekazu; Hayashi, Akira; Hara, Yuuko

    2000-01-01

    Phase III clinical study was performed to evaluate clinical utility of {sup 123}I-MIBG in the localization of tumors in 48 patients with tumors of sympathetic and adrenomedullary origin, diagnosed or strongly suspected. Sixteen patients had pheochromocytoma, 23 had neuroblastoma, 7 had medullary carcinoma of the thyroid, and 2 had Sipple syndrome. In 3 out of 48 patients, {sup 123}I-MIBG scintigraphy was performed twice. The clinical utility of {sup 123}I-MIBG was evaluated in 50 cases. Out of 140 lesions, {sup 123}I-MIBG scintigraphy demonstrated 51 true positive, 79 true negative, 1 false positive, and 2 false negative. Seven lesions were not evaluable. Sensitivity was 96.2%, Specificity was 98.8%, and Accuracy was 97.7%. An acquisition between 4 hrs and a day after injection was adequate for tumor detection. Neither adverse reactions nor abnormal laboratory findings were noted in relation to {sup 123}I-MIBG injections. Our study indicates that {sup 123}I-MIBG is a safe and useful radiotracer for visualization and localization of tumors of sympathetic and adrenomedullary origin. (author)

  14. 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.)

  15. Groundwater flow with energy transport and water-ice phase change: Numerical simulations, benchmarks, and application to freezing in peat bogs

    Science.gov (United States)

    McKenzie, J.M.; Voss, C.I.; Siegel, D.I.

    2007-01-01

    In northern peatlands, subsurface ice formation is an important process that can control heat transport, groundwater flow, and biological activity. Temperature was measured over one and a half years in a vertical profile in the Red Lake Bog, Minnesota. To successfully simulate the transport of heat within the peat profile, the U.S. Geological Survey's SUTRA computer code was modified. The modified code simulates fully saturated, coupled porewater-energy transport, with freezing and melting porewater, and includes proportional heat capacity and thermal conductivity of water and ice, decreasing matrix permeability due to ice formation, and latent heat. The model is verified by correctly simulating the Lunardini analytical solution for ice formation in a porous medium with a mixed ice-water zone. The modified SUTRA model correctly simulates the temperature and ice distributions in the peat bog. Two possible benchmark problems for groundwater and energy transport with ice formation and melting are proposed that may be used by other researchers for code comparison. ?? 2006 Elsevier Ltd. All rights reserved.

  16. Groundwater recharge: Accurately representing evapotranspiration

    CSIR Research Space (South Africa)

    Bugan, Richard DH

    2011-09-01

    Full Text Available Groundwater recharge is the basis for accurate estimation of groundwater resources, for determining the modes of water allocation and groundwater resource susceptibility to climate change. Accurate estimations of groundwater recharge with models...

  17. Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study.

    Science.gov (United States)

    Cohen, Ezra E W; Davis, Darren W; Karrison, Theodore G; Seiwert, Tanguy Y; Wong, Stuart J; Nattam, Sreenivasa; Kozloff, Mark F; Clark, Joseph I; Yan, Duen-Hwa; Liu, Wen; Pierce, Carolyn; Dancey, Janet E; Stenson, Kerstin; Blair, Elizabeth; Dekker, Allison; Vokes, Everett E

    2009-03-01

    Epidermal growth factor receptor (EGFR) is a validated target in squamous-cell carcinoma of the head and neck, but in patients with recurrent or metastatic disease, EGFR targeting agents have displayed modest efficacy. Vascular endothelial growth factor (VEGF)-mediated angiogenesis has been implicated as a mechanism of resistance to anti-EGFR therapy. In this multi-institutional phase I/II study we combined an EGFR inhibitor, erlotinib, with an anti-VEGF antibody, bevacizumab. Between April 15, 2003, and Jan 27, 2005, patients with recurrent or metastatic squamous-cell carcinoma of the head and neck were enrolled from seven centres in the USA and were given erlotinib (150 mg daily) and bevacizumab in escalating dose cohorts. The primary objectives in the phase I and II sections, respectively, were to establish the maximum tolerated dose and dose-limiting toxicity of bevacizumab when administered with erlotinib and to establish the proportion of objective responses and time to disease progression. Pretreatment serum and tissues were collected and analysed by enzyme-linked immunosorbent assay and immunofluorescence quantitative laser analysis, respectively. This study was registered with ClinicalTrials.gov, number NCT00055913. In the phase I section of the trial, ten patients were enrolled in three successive cohorts with no dose-limiting toxic effects noted. 46 patients were enrolled in the phase II section of the trial (including three patients from the phase I section) on the highest dose of bevacizumab (15 mg/kg every 3 weeks). Two additional patients were accrued beyond the protocol-stipulated 46, leaving a total of 48 patients for the phase II assessment. The most common toxic effects of any grade were rash and diarrhoea (41 and 16 of 48 patients, respectively). Three patients had serious bleeding events of grade 3 or higher. Seven patients had a response, with four showing a complete response allowing rejection of the null hypothesis. Median time of overall

  18. ICEBERG, Phase III. Appendix H

    Science.gov (United States)

    1945-05-06

    N r j O N 2 | < N | r -~~~~~~~~~~~~I-jI- H ol (9 0) _~ tq r~ >- U r 0 P- 0 ~nIJ p-i e * *I sF · L-- c~~J r3~~ ~~O~~~~~r CD , , . °OY O W @u upt eo a...tz C Ct < eo O el I’ Fffl C+ C Od 0~~~~~~~~~~~’ oq w~ O~ @r 0o . - O, OC 0 I O~~~~~~~~~~~~~~~~~~~~~~~~~~~~~C F CD ? -32sc .Fd IJ 0 t3L CD d r· c ; (p...present vrill include: Shore Based Supported fro;- forces afloat 10 LCT 9 DD 6 YMIS 20 LCIA 6 DE 2 PCS(H) 10 LCVP 6 PC(IJC) 1 QGP 4 YWTT 6 sc (Nc) 1 IRL

  19. A matched-pair cluster design study protocol to evaluate implementation of the Canadian C-spine rule in hospital emergency departments: Phase III

    Directory of Open Access Journals (Sweden)

    Rowe Brian H

    2007-02-01

    Full Text Available Abstract Background Physicians in Canadian emergency departments (EDs annually treat 185,000 alert and stable trauma victims who are at risk for cervical spine (C-spine injury. However, only 0.9% of these patients have suffered a cervical spine fracture. Current use of radiography is not efficient. The Canadian C-Spine Rule is designed to allow physicians to be more selective and accurate in ordering C-spine radiography, and to rapidly clear the C-spine without the need for radiography in many patients. The goal of this phase III study is to evaluate the effectiveness of an active strategy to implement the Canadian C-Spine Rule into physician practice. Specific objectives are to: 1 determine clinical impact, 2 determine sustainability, 3 evaluate performance, and 4 conduct an economic evaluation. Methods We propose a matched-pair cluster design study that compares outcomes during three consecutive 12-months "before," "after," and "decay" periods at six pairs of "intervention" and "control" sites. These 12 hospital ED sites will be stratified as "teaching" or "community" hospitals, matched according to baseline C-spine radiography ordering rates, and then allocated within each pair to either intervention or control groups. During the "after" period at the intervention sites, simple and inexpensive strategies will be employed to actively implement the Canadian C-Spine Rule. The following outcomes will be assessed: 1 measures of clinical impact, 2 performance of the Canadian C-Spine Rule, and 3 economic measures. During the 12-month "decay" period, implementation strategies will continue, allowing us to evaluate the sustainability of the effect. We estimate a sample size of 4,800 patients in each period in order to have adequate power to evaluate the main outcomes. Discussion Phase I successfully derived the Canadian C-Spine Rule and phase II confirmed the accuracy and safety of the rule, hence, the potential for physicians to improve care. What

  20. Study protocol of the SACURA trial: a randomized phase III trial of efficacy and safety of UFT as adjuvant chemotherapy for stage II colon cancer

    Directory of Open Access Journals (Sweden)

    Ishiguro Megumi

    2012-07-01

    Full Text Available Abstract Background Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy, but the usefulness of adjuvant chemotherapy for stage II colon cancer remains controversial. The major Western guidelines recommend adjuvant chemotherapy for “high-risk stage II” cancer, but this is not clearly defined and the efficacy has not been confirmed. Methods/design SACURA trial is a multicenter randomized phase III study which aims to evaluate the superiority of 1-year adjuvant treatment with UFT to observation without any adjuvant treatment after surgery for stage II colon cancer in a large population, and to identify “high-risk factors of recurrence/death” in stage II colon cancer and predictors of efficacy and adverse events of the chemotherapy. Patients aged between 20 and 80 years with curatively resected stage II colon cancer are randomly assigned to a observation group or UFT adjuvant therapy group (UFT at 500–600 mg/day as tegafur in 2 divided doses after meals for 5 days, followed by 2-day rest. This 1-week treatment cycle is repeated for 1 year. The patients are followed up for 5 years until recurrence or death. Treatment delivery and adverse events are entered into a web-based case report form system every 3 months. The target sample size is 2,000 patients. The primary endpoint is disease-free survival, and the secondary endpoints are overall survival, recurrence-free survival, and incidence and severity of adverse events. In an additional translational study, the mRNA expression of 5-FU-related enzymes, microsatellite instability and chromosomal instability, and histopathological factors including tumor budding are assessed to evaluate correlation with recurrences, survivals and adverse events. Discussion A total of 2,024 patients were enrolled from October 2006 to July 2010. The results of this study will provide important information that help to improve the

  1. Groundwater Managment Districts

    Data.gov (United States)

    Kansas Data Access and Support Center — This dataset outlines the location of the five Groundwater Management Districts in Kansas. GMDs are locally formed and elected boards for regional groundwater...

  2. A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Suenaga M

    2015-03-01

    Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Keisho Chin,1 Toshiharu Yamaguchi2 1Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan Background: Triweekly capecitabine plus irinotecan (XELIRI is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI in metastatic colorectal cancer (mCRC because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV as second-line chemotherapy for mCRC.Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin and BV and had a UGT1A1 genotype of wild-type or heterozygous for UGT1A1*6 or *28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5 mg/kg on day 1 every 2 weeks. The phase I study consisted of two steps (irinotecan 150 and 180 mg/m2, and dose-limiting toxicity was assessed during the first treatment cycle. The primary endpoint of the phase II study was progression-free survival (PFS.  Results: The recommended dose of irinotecan was determined to be 180 mg/m2 in the phase I study. Between November 2010 and August 2013, 44 patients were enrolled in phase II. The patients’ characteristics were as follows (N=44: median age, 60 years (range 32–80; male/female, 21/23; and UGT1A1 wild-type/heterozygous, 29/15. The median PFS was 6.8 months (95% confidence interval, 5.3–8.2 months, and the primary endpoint was met. Median overall survival was 18.3 months. The response rate was 22.7%. There was no significant difference in PFS or overall survival according to UGT1A1 status. Grade 3 or higher adverse events were mainly neutropenia in six

  3. Radiotherapy versus concurrent 5-day cisplatin and radiotherapy in locally advanced cervical carcinoma. Long-term results of a Phase III randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Viorica; Coza, Ovidiu; Ghilezan, Nicolae [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Radiation Oncology; ' Iuliu Hatieganu' Univ. of Medicine and Pharmacy, Cluj-Napoca (Romania); Ordeanu, Claudia; Todor, Nicolae [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Radiation Oncology; Traila, Alexandru [' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Surgery; Rancea, Alin [' Iuliu Hatieganu' Univ. of Medicine and Pharmacy, Cluj-Napoca (Romania); ' Ion Chiricuta' Cancer Institute, Cluj-Napoca (Romania). Dept. of Surgery

    2009-03-15

    Purpose: To prove the superiority of concurrent radiochemotherapy (RTCT) over radiotherapy (RT) alone in locally advanced cervical carcinoma. Patients and Methods: In this randomized monocentric phase III study, 566 patients with squamous cell carcinoma of the cervix were included: 284 in arm A (RT) and 282 in arm B (concurrent RTCT with cisplatin 20 mg/m{sup 2} x 5 days). 238 patients (42%) were in stage IIB, 209 (37%) in stage IIIA, and 119 (21%) in stage IIIB. The median follow-up was 62.8 months. RT to the pelvis was delivered to a dose of 46 Gy/23 fractions. A cervical boost was given using the X-ray arch technique or high-dose-rate intracavitary brachytherapy at a dose of 10 Gy. Thereafter, patients were evaluated: those with good response optionally underwent surgery and the others continued RT until 64 Gy/pelvis (with or without CT according to randomization) and 14 Gy/central tumor volume. Results: The 5-year survival rate was statistically significantly superior in the concurrent RTCT group (74%) versus the RT group (64%; p < 0.05). In patients undergoing surgery after RT or RTCT, superior results were obtained, compared to the nonoperated patients: 5-year survival rate 86% versus 53% (p < 0.01). 192 failures were recorded: 109 (38%) after RT alone versus 83 (29%) after concurrent RTCT (p < 0.01). Conclusion: The results of this study prove the obvious superiority of concurrent RTCT with 5-day cisplatin compared to RT alone in patients with locally advanced cervical carcinoma, regarding local control (78% vs. 67%) and 5-year survival rates (74% vs. 64%). (orig.)

  4. Voxel-based evidence of perfusion normalization in glioblastoma patients included in a phase I-II trial of radiotherapy/tipifarnib combination.

    Science.gov (United States)

    Ken, Soléakhéna; Deviers, Alexandra; Filleron, Thomas; Catalaa, Isabelle; Lotterie, Jean-Albert; Khalifa, Jonathan; Lubrano, Vincent; Berry, Isabelle; Péran, Patrice; Celsis, Pierre; Moyal, Elizabeth Cohen-Jonathan; Laprie, Anne

    2015-09-01

    We previously showed that the farnesyl transferase inihibitor, Tipifarnib induced vascularization normalization, oxygenation and radiosensitization in a pre-clinical glioblastoma (GBM) model. The aim of this study was to assess by dynamic-susceptibility-contrast MRI (DSC-MRI) the effect of radiotherapy (RT) and Tipifarnib combination on tumor perfusion in GBM patients. Eighteen patients with newly diagnosed GBM, enrolled in a phase I-II clinical trial associating RT with Tipifarnib, underwent anatomical MR imaging and DSC-MRI before (M0) and two months after treatment (M2). Anatomic volumes of interest (VOIs) were delineated according to contrast-enhanced and hyper-intense signal areas on T1-Gd and T2 images, respectively. Perfusion variations between M0 and M2 were assessed with median relative cerebral blood volume (rCBV) inside these VOIs. Another voxel by voxel analysis of CBV values classified 405,117 tumor voxels into High_, Normal_ and Low_CBVTUMOR according to the distribution of CBV in the contralateral normal tissue. These three categories of CBVTUMOR voxels were color-coded over anatomical MRI. Variations of median rCBV were significantly different for two groups of patients (P  1) and rCBV increased when initial rCBV was color-coded voxels provided additional spatial and quantitative information about tumor perfusion: Group_rCBV_M0 > 1 presented a significant decrease of High_CBVTUMOR volume (P = 0.015) simultaneously with a significant increase of Normal_CBVTUMOR volume (P = 0.009) after treatment. Group_rCBV_M0 perfusion evolution in GBM patients treated with RT combined to Tipifarnib; showing variations in favour of tumor perfusion normalization in agreement with our pre-clinical results of vascular normalization.

  5. Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer.

    Science.gov (United States)

    Tabernero, Josep; Ohtsu, Atsushi; Muro, Kei; Van Cutsem, Eric; Oh, Sang Cheul; Bodoky, György; Shimada, Yasuhiro; Hironaka, Shuichi; Ajani, Jaffer A; Tomasek, Jiri; Safran, Howard; Chandrawansa, Kumari; Hsu, Yanzhi; Heathman, Michael; Khan, Azhar; Ni, Lan; Melemed, Allen S; Gao, Ling; Ferry, David; Fuchs, Charles S

    2017-10-01

    Ramucirumab is an IgG1 monoclonal antibody specific for the vascular endothelial growth factor receptor-2. Ramucirumab, 8 mg/kg every 2 weeks, administered as monotherapy (REGARD) or in combination with paclitaxel (RAINBOW), was safe and effective in patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer. We evaluated exposure-efficacy and exposure-safety relationships of ramucirumab from two randomized, placebo-controlled phase III trials. Sparse pharmacokinetic samples were collected, and a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (Cmin,ss). Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the ramucirumab exposure (Cmin,ss)-efficacy relationship to overall survival (OS) and progression-free survival (PFS). Logistic regression analyses were used to evaluate exposure-safety relationships. Analyses included 321 ramucirumab + paclitaxel and 335 placebo + paclitaxel patients from RAINBOW and 72 ramucirumab and 35 placebo patients from REGARD. Exposure-efficacy analysis showed ramucirumab Cmin,ss was a significant predictor of OS and PFS in both trials. Higher ramucirumab exposure was associated with longer OS and PFS. In RAINBOW, grade ≥3 hypertension, leukopenia, and neutropenia, but not febrile neutropenia, significantly correlated with Cmin,ss, with increased exposure leading to increased incidence. Exploratory exposure-response analyses suggest a positive relationship between efficacy and ramucirumab exposure with manageable toxicities at exposures generated from a dose of 8 mg/kg ramucirumab given every 2 weeks for patients with advanced gastric/GEJ cancer. These findings suggest an opportunity to further optimize benefit versus risk profiles of ramucirumab treatment in patients with gastric/GEJ cancer. Mol Cancer Ther; 16(10); 2215-22. ©2017 AACR. ©2017 American Association for Cancer Research.

  6. The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines

    Directory of Open Access Journals (Sweden)

    Sanvictores Diozele Hazel M

    2012-06-01

    Full Text Available Abstract Background A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration Current Controlled Trials ISRCTN62323832

  7. Secukinumab and Sustained Improvement in Signs and Symptoms of Patients With Active Ankylosing Spondylitis Through Two Years: Results From a Phase III Study.

    Science.gov (United States)

    Marzo-Ortega, H; Sieper, J; Kivitz, A; Blanco, R; Cohen, M; Martin, R; Readie, A; Richards, H B; Porter, B

    2017-07-01

    Secukinumab improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks in the phase III MEASURE 2 study. Here, we report longer-term (104 weeks) efficacy and safety results. Patients with active AS were randomized to subcutaneous secukinumab 150 mg, 75 mg, or placebo at baseline; weeks 1, 2, and 3; and every 4 weeks from week 4. The primary end point was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16. Other end points included ASAS40, high-sensitivity C-reactive protein, ASAS5/6, Bath Ankylosing Spondylitis Disease Activity Index, Short Form 36 health survey physical component summary, ASAS partial remission, EuroQol 5-domain measure, and Functional Assessment of Chronic Illness Therapy fatigue subscale. End points were assessed through week 104, with multiple imputation for binary variables and a mixed-effects model repeated measures for continuous variables. Of 219 randomized patients, 60 of 72 (83.3%) and 57 of 73 (78.1%) patients completed 104 weeks of treatment with secukinumab 150 mg and 75 mg, respectively; ASAS20/ASAS40 response rates at week 104 were 71.5% and 47.5% with both secukinumab doses, respectively. Clinical improvements with secukinumab were sustained through week 104 across all secondary end points. Across the entire treatment period (mean secukinumab exposure 735.6 days), exposure-adjusted incidence rates for serious infections and infestations, Crohn's disease, malignant or unspecified tumors, and major adverse cardiac events with secukinumab were 1.2, 0.7, 0.5, and 0.7 per 100 patient-years, respectively. No cases of tuberculosis reactivation, opportunistic infections, or suicidal ideation were reported. Secukinumab provided sustained improvement through 2 years in the signs and symptoms of AS, with a safety profile consistent with previous reports. © 2017 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of

  8. A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.

    Science.gov (United States)

    Planchard, David; Yokoi, Takashi; McCleod, Michael J; Fischer, Jürgen R; Kim, Young-Chul; Ballas, Marc; Shi, Kelvin; Soria, Jean-Charles

    2016-05-01

    Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing.

  9. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy

    Science.gov (United States)

    Emery, Paul; Vencovský, Jiří; Sylwestrzak, Anna; Leszczyński, Piotr; Porawska, Wieslawa; Baranauskaite, Asta; Tseluyko, Vira; Zhdan, Vyacheslav M; Stasiuk, Barbara; Milasiene, Roma; Barrera Rodriguez, Aaron Alejandro; Cheong, Soo Yeon; Ghil, Jeehoon

    2017-01-01

    Objectives To compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. Methods This is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured. Results 596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was −9.41% to 4.98%, which is completely contained within the predefined equivalence margin of −15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%). Conclusions SB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN. Trial registration numbers NCT01895309, EudraCT 2012-005026-30. PMID:26150601

  10. Immunogenicity and safety of a cell culture-based quadrivalent influenza vaccine in adults: A Phase III, double-blind, multicenter, randomized, non-inferiority study

    Science.gov (United States)

    Bart, Stephan; Cannon, Kevin; Herrington, Darrell; Mills, Richard; Forleo-Neto, Eduardo; Lindert, Kelly; Abdul Mateen, Ahmed

    2016-01-01

    ABSTRACT Quadrivalent influenza vaccines (QIVs), which include both B lineage strains, are expected to provide broader protection than trivalent influenza vaccines (TIVs). The non-inferiority, immunogenicity, and safety of a cell culture-based investigational QIVc and 2 TIVs (TIV1c, TIV2c), in adults (≥18 y), were evaluated in this Phase III, double-blind, multicenter study. A total of 2680 age-stratified subjects were randomized (2:1:1) to receive 1 dose of QIVc (n = 1335), TIV1c (n = 676), or TIV2c (n = 669). TIV1c (B/Yamagata) and TIV2c (B/Victoria) differed only in B strain lineage. The primary objective was to demonstrate non-inferiority of the hemagglutinin-inhibition antibody responses of QIVc against TIVc, 22 d post-vaccination. Secondary objectives included the evaluation of immunogenicity of QIVc and TIVc in younger (≥18 – <65 y) and older (≥65 y) adults. Hemagglutinin inhibition assays were performed at days 1 and 22. Solicited local and systemic adverse events (AEs) were monitored for 7 d post-vaccination, and unsolicited AEs and serious AEs until day 181. QIVc met the non-inferiority criteria for all 4 vaccine strains and demonstrated superiority for both influenza B strains over the unmatched B strain included in the TIV1c and TIV2c, when geometric mean titers and seroconversion rates with TIVc were compared at day 22. Between 48%–52% of subjects experienced ≥1 solicited AE, the most common being injection-site pain and headache. Serious AEs were reported by ≤1% of subjects, none were vaccine-related. The results indicate that QIVc is immunogenic and well tolerated in both younger and older adults. The immunogenicity and safety profiles of QIVc and TIVc were comparable at all ages evaluated. PMID:27322354

  11. Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer.

    Science.gov (United States)

    Chang, Joe Y; Zhang, Wencheng; Komaki, Ritsuko; Choi, Noah C; Chan, Shen; Gomez, Daniel; O'Reilly, Michael; Jeter, Melenda; Gillin, Michael; Zhu, Xiaorong; Zhang, Xiaodong; Mohan, Radhe; Swisher, Stephen; Hahn, Stephen; Cox, James D

    2017-02-01

    The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.5Gy/fraction of proton therapy. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time was 83.1months (95% CI: 69.2-97.1months). For all 35 patients, the 1, 3, and 5-year overall survival rates were 85.7%, 42.9%, and 28.1%, respectively. The 5-year local recurrence-free, regional recurrence-free, and distant metastasis-free survival rates were 85.0%, 89.2%, and 54.4%, respectively. Different T stages had no effect on local and regional recurrence (p=0.499, p=1.00). However, with the increase in T stages, the distant metastasis rate increased significantly (p=0.006). The most common adverse effects were dermatitis (grade 2, 51.4%; grade 3, 2.9%) and radiation pneumonitis (grade 2, 11.4%; grade 3, 2.9%). Other grade 2 toxicities included esophagitis (2.9%), rib fracture (2.9%), heart toxicities (5.7%), and chest wall pain (2.9%). According to our long-term follow-up data, proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. Systemic therapy should be considered to reduce the rate of distant metastasis in cases of T2 and T3 lesions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization.

    Science.gov (United States)

    Tournaye, Herman; Sukhikh, Gennady T; Kahler, Elke; Griesinger, Georg

    2017-05-01

    Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation? Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin. MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration. Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to Pharmaceuticals Division. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Besins, Ferring and Mithra (now Allergan) and H.T. has received consultancy fees from Finox, Ferring, Abbott, ObsEva and Ovascience. G.S. has nothing to disclose. E.K. is an employee of Abbott GmbH. G.G. has received investigator fees from Abbott during the conduct of the study; outside of this submitted work, G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, Glycotope, as well as personal fees from VitroLife, NMC Healthcare LLC, ReprodWissen LLC and ZIVA LLC. NCT01850030 (clinicaltrials.gov). 19 April 2013. 23 August 2013.

  13. Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Varveris, H.; Kachris, S.; Lyraraki, E.; Petineli, E.; Varveris, A.; Fasoulaki, A. [Dept. of Radiotherapy and Oncology, Medical School of Crete Univ., Iraclion Univ. Hospital (Greece); Mazonakis, M.; Tzedakis, A. [Dept. of Medical Physics, Medical School of Crete Univ., Iraclion Univ. Hospital (Greece); Kouloulias, V. [Dept. of Radiotherapy and Oncology, Medical School of Athens Univ. (Greece); Zolindaki, A. [Dept. of Obstetrics and Gynecology, Medical School of Crete Univ., Iraclion Univ. Hospital (Greece); Vlachaki, M. [New York Univ. Medical Center, NY (United States)

    2006-03-15

    Background and Purpose: although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. Patients and Methods: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m{sup 2}/week was increased in 5-mg/m{sup 2} increments to two levels. The standard dose of CDDP was 20-25 mg/m{sup 2}/week. Results: concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m{sup 2}/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). Conclusion: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m{sup 2}/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising. (orig.)

  14. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Terhaard, Chris H. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Doornaert, Patricia A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Bijl, Hendrik P. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Ende, Piet van den [Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht (Netherlands); Chin, Alim [Department of Clinical Oncology, Leiden University Medical Centre, Leiden (Netherlands); Pop, Lucas A.; Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  15. Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial

    Science.gov (United States)

    ANTONILLI, MORENA; RAHIMI, HASSAN; VISCONTI, VALERIA; NAPOLETANO, CHIARA; RUSCITO, ILARY; ZIZZARI, ILARIA GRAZIA; CAPONNETTO, SALVATORE; BARCHIESI, GIACOMO; IADAROLA, ROBERTA; PIERELLI, LUCA; RUGHETTI, AURELIA; BELLATI, FILIPPO; PANICI, PIERLUIGI BENEDETTI; NUTI, MARIANNA

    2016-01-01

    Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments. PMID:26892612

  16. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Directory of Open Access Journals (Sweden)

    L John Hoffer

    Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

  17. Prognostic score for second-line chemotherapy of advanced non-small-cell lung cancer: external validation in a phase III trial comparing vinflunine with docetaxel.

    Science.gov (United States)

    Di Maio, Massimo; Krzakowski, Maciej; Fougeray, Ronan; Kowalski, Dariusz M; Gridelli, Cesare

    2012-07-01

    A prognostic index for second-line chemotherapy of NSCLC was previously developed, based on individual patient data (IPD) of nine randomized trials. In order to validate the prognostic score in an external dataset, we analysed IPD of a non-inferiority phase III trial comparing vinflunine vs. docetaxel in second-line treatment of advanced NSCLC. Primary endpoint of this analysis was overall survival (OS). The following variables were considered for survival analysis and score calculation: gender, performance status, stage of disease, tumour histology, type of first-line treatment, response to first-line treatment. Cox model, stratified by treatment arm, was used for multivariate analysis. Individual prognostic scores were derived, and patients were divided into 3 categories: 9 (worst). All 551 patients enrolled in the trial had complete information for the calculation of prognostic score. Median OS in the whole group was 6.9 months, with similar efficacy in the two treatment arms. Median OS was 12.9, 6.9 and 3.8 months in the best, intermediate and worst category, respectively. Cox model showed a significant effect comparing intermediate vs. best category (Hazard Ratio 1.79, 95%CI 1.31-2.47, p=0.0003) and comparing worst vs. best category (Hazard Ratio 3.25, 95%CI 2.18-4.83, pmodel was high (0.926), indicating a good discrimination according to the proposed three risk categories. Prognostic ability of our score for candidates to second-line treatment in advanced NSCLC was successfully validated, allowing the identification of subgroups of patients with more vs. less favourable outcome. Prognostic score could be useful in daily decision-making in clinical practise, because a better understanding of factors conditioning life expectancy of patients could greatly help a careful evaluation of risks and benefits associated with therapeutic decisions.

  18. Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study

    Energy Technology Data Exchange (ETDEWEB)

    Spanos, W.J. Jr.; Wasserman, T.; Meoz, R.; Sala, J.; Kong, J.; Stetz, J.

    1987-10-01

    Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses.

  19. Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: A Gynecologic Oncology Group Study.

    Science.gov (United States)

    Burger, Robert A; Brady, Mark F; Bookman, Michael A; Monk, Bradley J; Walker, Joan L; Homesley, Howard D; Fowler, Jeffrey; Greer, Benjamin E; Boente, Matthew; Fleming, Gini F; Lim, Peter C; Rubin, Stephen C; Katsumata, Noriyuki; Liang, Sharon X

    2014-04-20

    To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage. Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.

  20. Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study

    Science.gov (United States)

    Pepin, Stephanie; Szymanski, Henryk; Rochín Kobashi, Ilya Angélica; Villagomez Martinez, Sandra; González Zamora, José Francisco; Brzostek, Jerzy; Huang, Li-Min; Chiu, Cheng-Hsun; Chen, Po-Yen; Ahonen, Anitta; Forstén, Aino; Seppä, Ilkka; Quiroz, René Farfán; Korhonen, Tiina; Rivas, Enrique; Monfredo, Celine; Hutagalung, Yanee; Menezes, Josemund; Vesikari, Timo

    2016-01-01

    ABSTRACT A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3–8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3–8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain. PMID:27565435

  1. A double-blind, randomized, and active-controlled phase III study of Herbiron drink in the treatment of iron-deficiency anemia in premenopausal females in Taiwan

    Directory of Open Access Journals (Sweden)

    Ching-Tzu Lee

    2016-06-01

    Full Text Available Background: About 468 million non-pregnant women are estimated to suffer from iron-deficiency anemia (IDA worldwide. The highest prevalence of IDA occurs in the Taiwanese population. Objective: To evaluate the effectiveness of Herbiron to increase iron absorption in women with IDA. Design: Phase III double-blind, randomized, active-controlled, and parallel comparative study enrolled 124 patients with IDA and consisted of a 2-week run-in period, randomization, 12 weeks of supplementation, and 4 weeks of follow-up. The treatment group received Herbiron drink 50 mL p.o., b.i.d., before meals (daily iron intake: 21 mg/day plus placebo tablets. The control group received a ferrous sulfate tablet, t.i.d., plus placebo 50-mL drink before meals (daily iron intake: 195 mg/day. Results: Both treatments significantly improved hemoglobin and all secondary efficacy endpoints. Most IDA patients treated with Herbiron or ferrous sulfate finished the study in the normal range. Ferrous sulfate treatment induced a rapid rate of hemoglobin synthesis, which plateaued by week 8, whereas Herbiron treatment increased the rate of hemoglobin synthesis more slowly, likely due to its nine-fold lower iron content. Gastrointestinal adverse events (diarrhea, abdominal pain, dyspepsia, and nausea but not infectious adverse events were significantly more common in the ferrous sulfate group (n=11, 18.3% than those in the Herbiron group (n=1, 1.6% (p=0.004. Conclusion: Twelve weeks of Herbiron treatment delivering 21mg of iron or ferrous sulfate treatment delivering 195 mg of iron induced normal hemoglobin levels in 62 or 91% of non-pregnant women with IDA in Taiwan, respectively, suggesting dose-dependent and bioavailability effects.

  2. A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB project

    Directory of Open Access Journals (Sweden)

    Merle Corinne SC

    2012-05-01

    Full Text Available Abstract Background There have been no major advances in tuberculosis (TB drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385. Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically

  3. The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non-cystic fibrosis bronchiectasis.

    Science.gov (United States)

    Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; De Soyza, Anthony; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

    2017-07-01

    The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients. The RESPIRE programme consists of two international phase III prospective, parallel-group, randomized, double-blinded, multicentre, placebo-controlled trials of the same design. Adult patients with idiopathic or post-infectious NCFB, a history of ≥2 exacerbations in the previous 12months, and positive sputum culture for one of seven pre-specified pathogens, undergo stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or placebo using a pocket-sized inhaler in one of two regimens: 28days on/off treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8-week follow-up after the last dose. The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation. Secondary endpoints, including frequency of events using different exacerbation definitions, microbiology, quality of life and lung function will also be evaluated. The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria and stratified randomization, the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy. Additionally RESPIRE will increase understanding of NCFB treatment and could lead to an important new therapy for sufferers. The RESPIRE trials are registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration

  4. Phase III, randomised, multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-alpha for metastatic renal cell cancer.

    Science.gov (United States)

    Passalacqua, Rodolfo; Buzio, Carlo; Buti, Sebastiano; Porta, Camillo; Labianca, Roberto; Pezzuolo, Debora; Camisa, Roberta; Sabbatini, Roberto; Benecchi, Luigi; Messina, Caterina; Cengarle, Rita; Vaglio, Augusto; Dalla Chiesa, Matteo; Tomasello, Gianluca; Caminiti, Caterina

    2010-04-01

    This is the first phase III randomised trial to evaluate maintenance immunotherapy in metastatic renal cell cancer (mRCC). Patients were randomised to receive treatment with a 4-week cycle of subcutaneous low doses IL-2 + IFN in months 1, 3 and 5, and then every 3 months until the first documented disease progression (arm A, suspension), or the same regimen, with chronic maintenance of immunotherapy, regardless of tumour response, until death or intolerable toxicity (arm B, maintenance). The primary endpoint was overall survival (OS); secondary endpoints were time from first progression to death (TFPTD) and tolerability. One hundred and eighty-three patients were enrolled between January 1998 and November 2003. After a median follow-up of 53.9 months, response rate, median OS and median TFPTD were 14.7% (6.3% CR) versus 11.3% (5.5% CR), 14 versus 14 months, 6 versus 5 months, in arms A and B, respectively with no significant differences between the groups. Cox regression analysis showed that the use of chemotherapy after first progression (HR 0.54; 95% CI 0.35-0.86; p = 0.008), PS = 0 (HR 0.53; 95% CI 0.35-0.81; p = 0.001) and female gender (HR 0.63; 95% CI 0.41-0.98; p = 0.038) were significantly associated with a longer TFPTD; treatment arm was not significant (HR 0.88; 95% CI 0.60-1.31; p = 0.54). Toxicity was mainly limited to WHO grades 1 or 2. Chronic maintenance immunotherapy after disease progression is feasible, but does not significantly increase OS or the TFPTD.

  5. A phase III, randomized controlled study to assess the safety and immunogenicity of a semi-synthetic diphtheria, tetanus and whole-cell pertussis vaccine in Indian infants.

    Science.gov (United States)

    Sharma, Hitt; Patil, Vishwanath; Sharma, Dharambhushan; Kapre, Subhash; Jadhav, Suresh; Ravetkar, Satish; Kumar, Rakesh; Bahl, Sunil; Parekh, Sameer; Chakravarty, Anita

    2012-09-21

    Reactions to DTwP vaccine are well known and are a matter of great concern, much for the development of next generation combination vaccines. To avoid such reactions which occur from foreign compounds, WHO suggested manufacture of DTwP vaccine using semi-synthetic medium. The phase III trial reported here was conducted to assess the immunogenicity, tolerability and safety of a new DTwP vaccine manufactured using semi-synthetic medium for both tetanus and diphtheria toxoids in comparison with the routinely manufactured DTwP vaccine. In all, 331 infants aged 6-8 weeks were enrolled, out of which 308 completed the study. The vaccination was done at 6-10-14 weeks following EPI/WHO recommended immunization schedule. Blood samples were collected prior to the administration of first dose and one month after the third dose. Postvaccination, geometric mean titres for each component did not differ significantly amongst the two study groups. Though, the immunogenicity results were comparable between the two vaccines, the incidence of adverse events was comparatively low in semi-synthetic vaccine as against the routine vaccine group for all the three doses. The semi-synthetic DTwP vaccine was immunogenic and showed a significant lower incidence of local adverse events in comparison to the routine vaccine. This vaccine is now being used in the routine vaccination programme both as a triple antigen (DTwP alone) as well as a combination with Hepatitis B and/or Haemophilus influenzae type b vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study.

    Science.gov (United States)

    Sundy, John S; Schumacher, H Ralph; Kivitz, Alan; Weinstein, Steven P; Wu, Richard; King-Davis, Shirletta; Evans, Robert R

    2014-08-01

    To evaluate the safety and efficacy of once-weekly subcutaneous rilonacept 160 mg for prevention of gout flares in patients initiating or continuing urate-lowering therapy (ULT). This phase III study was conducted in the United States, South Africa, Europe, and Asia. Adults (n = 1315, 18-80 yrs) with gout, who were initiating or continuing ULT, were randomized to treatment with weekly subcutaneous injections of rilonacept 160 mg or placebo for 16 weeks followed by a 4-week safety followup. The primary endpoint was safety, assessed by adverse events (AE) and laboratory values. Efficacy was a secondary endpoint. Demographic and clinical characteristics were similar between treatments; predominantly male (87.8%), mean age 52.7 ± 11.3 years. Patients with ≥ 1 AE were 66.6% with rilonacept versus 59.1% placebo, with slightly more AE-related withdrawals with rilonacept (4.7% vs 3.0%) because of the greater incidence of injection site reactions (15.2% rilonacept, 3.3% placebo). Serious AE were similar in both groups, as were serious infections (0.9% placebo, 0.5% rilonacept); no tuberculosis or opportunistic infections occurred. Most common AE were headache, arthralgia, injection site erythema, accidental overdose, and pain in extremity. Of the 6 deaths, only 1 in the placebo group was considered treatment-related. At Week 16, rilonacept resulted in 70.3% fewer gout flares per patient (p gout flares (p gout flare days (p gout flares. Clinicaltrials.gov identifier NCT00856206; EudraCT No. 2008-007784-16.

  7. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial.

    Science.gov (United States)

    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

    2017-07-04

    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 cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl(-1)) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.Leukemia advance online publication, 1 August 2017; doi:10.1038/leu.2017.211.

  8. Gemcitabine mono-therapy versus gemcitabine plus targeted therapy in advanced pancreatic cancer: a meta-analysis of randomized phase III trials.

    Science.gov (United States)

    Ottaiano, Alessandro; Capozzi, Monica; De Divitiis, Chiara; De Stefano, Alfonso; Botti, Gerardo; Avallone, Antonio; Tafuto, Salvatore

    2017-03-01

    Prognosis of advanced pancreatic cancer is dismal and the novel targeted therapies, albeit successfully used to treat many advanced tumors, have shown modest results. We performed a meta-analysis in order to quantify the effect size on survival of adding targeted therapy to single agent gemcitabine. Randomized phase III trials comparing gemcitabine mono-therapy versus gemcitabine plus a targeted agent in first-line treatment of advanced pancreatic cancer designed on survival as primary outcome were selected. Search was done through Medline and the registry of the NIH. Keywords used for searching were 'pancreas', 'pancreatic', 'gemcitabine'. Study quality was assessed with MERGE criteria. Findings were depicted in classical Forest plots. Publication bias was evaluated by the construction of funnel plot. Nine studies met the meta-analysis inclusion criteria including 4564 patients. The target therapies were: erlotinib, cetuximab, rigosertib, elpamotide, bevacizumab, aflibercept, axitinib, masitinib and ganitumab. There was no statistically significant heterogeneity among the nine trials (p = 0.77). The hazard ratio (HR) of the pooled analysis was 0.998 (CI 95%: 0.932-1.068). Subgroup meta-analysis was also performed in anti-EGFR and anti-angiogenesis trials: the pooled HR were 0.94 (CI 95%: 0.705-1.175) and 1.055 (CI 95%: 0.913-1.197), respectively. The present meta-analysis does not show significant improvements in survival for targeted drugs in advanced pancreatic cancer. The possible reason of these results could be linked to the biology of pancreatic cancer as well as to the absence of predictive factors.

  9. STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

    Science.gov (United States)

    Chibaudel, Benoist; Bonnetain, Franck; Tournigand, Christophe; de Larauze, Marine Hug; de Gramont, Armand; Laurent-Puig, Pierre; Paget, Jérôme; Hadengue, Alexandra; Notelet, Dominique; Benetkiewicz, Magdalena; André, Thierry; de Gramont, Aimery

    2015-07-04

    The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013

  10. FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Macbeth Fergus R

    2009-10-01

    Full Text Available Abstract Background Venous thromboembolism (VTE occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus. VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN, a type of LMWH, to standard treatment for patients with lung cancer. Methods/Design The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE free survival, serious adverse events (SAEs, metastasis-free survival, toxicity, quality of life (QoL, levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. Trial registration Current Controlled Trials ISRCTN80812769

  11. Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.

    Science.gov (United States)

    Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M

    2009-12-01

    Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.

  12. Revisiting dosing regimen using PK/PD modeling: the MODEL1 phase I/II trial of docetaxel plus epirubicin in metastatic breast cancer patients.

    Science.gov (United States)

    Hénin, Emilie; Meille, Christophe; Barbolosi, Dominique; You, Benoit; Guitton, Jérôme; Iliadis, Athanassios; Freyer, Gilles

    2016-04-01

    The MODEL1 trial is the first model-driven phase I/II dose-escalation study of densified docetaxel plus epirubicin administration in metastatic breast cancer patients, a regimen previously known to induce unacceptable life-threatening toxicities. The primary objective was to determine the maximum tolerated dose of this densified regimen. Study of the efficacy was a secondary objective. Her2-negative, hormone-resistant metastatic breast cancer patients were treated with escalating doses of docetaxel plus epirubicin every 2 weeks for six cycles with granulocyte colony stimulating factor support. A total of 16 patients were treated with total doses ranging from 85 to 110 mg of docetaxel plus epirubicin per cycle. Dose escalation was controlled by a non-hematological toxicity model. Dose densification was guided by a model of neutrophil kinetics, able to optimize docetaxel plus epirubicin dosing with respect to pre-defined acceptable levels of hematological toxicity while ensuring maximal efficacy. The densified treatment was safe since hematological toxicity was much lower compared to previous findings, and other adverse events were consistent with those observed with this regimen. The maximal tolerated dose was 100 mg given every 2 weeks. The response rate was 45 %; median progression-free survival was 10.4 months, whereas 54.6 months of median overall survival was achieved. The optimized docetaxel plus epirubicin dosing regimen led to fewer toxicities associated with higher efficacy as compared with standard or empirical densified dosing. This study suggests that model-driven dosage adjustment can lead to improved efficacy-toxicity balance in patients with cancer when several anticancer drugs are combined.

  13. A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients.

    Science.gov (United States)

    Rodriguez, Pedro C; Popa, Xitllaly; Martínez, Odeth; Mendoza, Silvia; Santiesteban, Eduardo; Crespo, Tatiana; Amador, Rosa M; Fleytas, Ricardo; Acosta, Soraida C; Otero, Yanine; Romero, Gala N; de la Torre, Ana; Cala, Mireysi; Arzuaga, Lina; Vello, Loisel; Reyes, Delmairis; Futiel, Niurka; Sabates, Teresa; Catala, Mauricio; Flores, Yoanna I; Garcia, Beatriz; Viada, Carmen; Lorenzo-Luaces, Patricia; Marrero, Maria A; Alonso, Liuba; Parra, Jenelin; Aguilera, Nadia; Pomares, Yaisel; Sierra, Patricia; Rodríguez, Gryssell; Mazorra, Zaima; Lage, Agustin; Crombet, Tania; Neninger, Elia

    2016-08-01

    EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction. To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline. Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma.

    Science.gov (United States)

    Motzer, Robert J; Haas, Naomi B; Donskov, Frede; Gross-Goupil, Marine; Varlamov, Sergei; Kopyltsov, Evgeny; Lee, Jae Lyun; Melichar, Bohuslav; Rini, Brian I; Choueiri, Toni K; Zemanova, Milada; Wood, Lori A; Reaume, M Neil; Stenzl, Arnulf; Chowdhury, Simon; Lim, Ho Yeong; McDermott, Ray; Michael, Agnieszka; Bao, Weichao; Carrasco-Alfonso, Marlene J; Aimone, Paola; Voi, Maurizio; Doehn, Christian; Russo, Paul; Sternberg, Cora N

    2017-09-13

    Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT600mg), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT800mg) and safety. Results The primary analysis results of DFS ITT600mg favored pazopanib but did not show a significant improvement over placebo (hazard ratio [HR], 0.86; 95% CI, 0.70 to 1.06; P = .165). The secondary analysis of DFS in ITT800mg (n = 403) yielded an HR of 0.69 (95% CI, 0.51 to 0.94). Follow-up analysis in ITT600mg yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting.

  15. Final efficacy and updated safety results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer.

    Science.gov (United States)

    Bell, R; Brown, J; Parmar, M; Toi, M; Suter, T; Steger, G G; Pivot, X; Mackey, J; Jackisch, C; Dent, R; Hall, P; Xu, N; Morales, L; Provencher, L; Hegg, R; Vanlemmens, L; Kirsch, A; Schneeweiss, A; Masuda, N; Overkamp, F; Cameron, D

    2017-04-01

    The purpose of this analysis was to assess the long-term impact of adding bevacizumab to adjuvant chemotherapy for early triple-negative breast cancer (TNBC). Patients eligible for the open-label randomized phase III BEATRICE trial had centrally confirmed triple-negative operable primary invasive breast cancer (pT1a-pT3). Investigators selected anthracycline- and/or taxane-based chemotherapy for each patient. After definitive surgery, patients were randomized 1:1 to receive ≥4 cycles of chemotherapy alone or with 1 year of bevacizumab (5 mg/kg/week equivalent). Stratification factors were nodal status, selected chemotherapy, hormone receptor status, and type of surgery. The primary end point was invasive disease-free survival (IDFS; previously reported). Secondary outcome measures included overall survival (OS) and safety. After 56 months' median follow-up, 293 of 2591 randomized patients had died. There was no statistically significant difference in OS between treatment arms in either the total population (hazard ratio 0.93, 95% confidence interval [CI] 0.74-1.17; P = 0.52) or pre-specified subgroups. The 5-year OS rate was 88% (95% CI 86-90%) in both treatment arms. Updated IDFS results were consistent with the primary IDFS analysis. Five-year IDFS rates were 77% (95% CI 75-79%) with chemotherapy alone versus 80% (95% CI 77-82%) with bevacizumab. From 18 months after first study dose to study end, new grade ≥3 adverse events occurred in 4.6% and 4.5% of patients in the two arms, respectively. Final OS results showed no significant benefit from bevacizumab therapy for early TNBC. Late-onset toxicities were rare in both groups. Five-year OS and IDFS rates suggest that the prognosis for patients with TNBC is better than previously thought. NCT00528567.

  16. Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: A phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Amichetti, M.; Graiff, C.; Fellin, G.; Pani, G.; Bolner, A.; Maluta, S. (Divisione di Radioterapia Oncologica, Trento (Italy)); Valdagni, R. (Divisione di Radioterapia Oncologica, Trento (Italy) Istituto per la Ricerca Scientifica e Tecnologica, Trento (Italy))

    1993-08-01

    Hyperthermia is now being widely used to treat clinical malignancies, especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplantin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m[sup 2] iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5[degrees]C for 30 min). Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systematic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, they observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change. The study confirms the feasibility of the combination of cisplantin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors. 43 refs., 3 figs., 4 tabs.

  17. The efficacy and safety of bevacizumab combined with chemotherapy in treatment of HER2-negative metastatic breast cancer: a meta-analysis based on published phase III trials.

    Science.gov (United States)

    Fang, Yuan; Qu, Xinlan; Cheng, Boran; Chen, Yuanyuan; Wang, Zhenmeng; Chen, Fangfang; Xiong, Bin

    2015-03-01

    Bevacizumab (Bev) combined with chemotherapy significantly improves progression-free survival (PFS) but not overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The efficacy and safety depend on the type of chemotherapy combined with Bev. We performed a meta-analysis of phase III trials to evaluate the efficacy and safety of Bev + standard chemotherapy for HER2-negative MBC. The Cochrane Central Register of Controlled Trials, the Cochrane databases, EMBASE, MEDLINE, and ClinicalTrials.gov were analyzed. The primary outcomes included PFS, OS, and toxicity. Event-based hazard ratios (HRs) and relative risks (RRs) were expressed with the 95% confidence intervals (CIs). Four randomized controlled trials consisting of 3082 patients were included. Bev + standard chemotherapy improved PFS (HR 0.70, CI 0.64-0.77, P = 0.000) but had no effect on OS (HR 0.92, CI 0.82-1.02, P = 0.119). Bev + chemotherapy increased the incidence of febrile neutropenia (RR 1.45, CI 1.00 to 2.09, P = 0.048), proteinuria (RR 11.68, CI 3.72-36.70, P = 0.000), sensory neuropathy (RR 1.33, CI 1.05-1.70, P = 0.020), and grade ≥3 hypertension (RR 13.94, CI 7.06-27.55, P = 0.000). No differences in efficacy were observed between Bev + paclitaxel and Bev + capecitabine (Cape), but Bev + Cape increased the incidence of neutropenia. Bev + standard chemotherapy improved PFS in HER2-negative MBC patients. No benefit in OS was observed. Bev + Cape and Bev + paclitaxel had similar treatment efficacy, but Bev + Cape had a higher incidence of neutropenia.

  18. Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial.

    Science.gov (United States)

    Janssens, Geert O; Terhaard, Chris H; Doornaert, Patricia A; Bijl, Hendrik P; van den Ende, Piet; Chin, Alim; Pop, Lucas A; Kaanders, Johannes H

    2012-02-01

    To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199

    Science.gov (United States)

    Adams, Sylvia; Gray, Robert J.; Demaria, Sandra; Goldstein, Lori; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Wang, Molin; Jones, Vicky E.; Saphner, Thomas J.; Wolff, Antonio C.; Wood, William C.; Davidson, Nancy E.; Sledge, George W.; Sparano, Joseph A.; Badve, Sunil S.

    2014-01-01

    Purpose Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Patients and Methods Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. Results The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. Conclusion In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter. PMID:25071121

  20. Safety and immunogenicity of Bio Pox™, a live varicella vaccine (Oka strain) in Indian children: A comparative multicentric, randomized phase II/III clinical trial.

    Science.gov (United States)

    Dubey, Anand Prakash; Faridi, Mohammad Moonis Akbar; Mitra, Monjori; Kaur, Iqbal Rajinder; Dabas, Aashima; Choudhury, Jaydeep; Mukherjee, Mallar; Mishra, Devendra

    2017-09-02

    Varicella or chickenpox is a highly contagious disease with a high secondary attack rate. Almost 30% of Indian adolescents lack protective antibodies against varicella, emphasizing the need of routine varicella immunization. The Oka VZV is a well-established, safe and efficacious vaccine strain that is highly immunogenic and produces lifelong protective immunity. The present multicentric, open label, randomized, controlled Phase II/III study, compared the Bio Pox™ (indigenous investigational vaccine) with a licensed vaccine, Varivax™ ([a])([a]) Please note that this article refers to the product named VARIVAX as manufactured by Changchun Keygen Biological Products Ltd., China and marketed in India by VHB Life Sciences Limited, Mumbai, and not the product VARIVAX® owned by Merck Sharp & Dohme Corp., Rahway, New Jersey, USA. Merck Sharp & Dohme Corp. have asked us to make clear that the product manufactured by Changchun Keygen Biological Products Ltd. is unrelated to and is not sponsored, endorsed or otherwise authorised by Merck Sharp & Dohme Corp. , for its safety and immunogenicity profile in 252 healthy subjects in the age group of 1-12 y (cohort I: 6-12 years, II:1-6 years) in 3 tertiary medical institutions. Antibodies were measured by VZV Glycoprotein Enzyme Linked Immunoassay (IgG ELISA) kit. Seroconversion percentage in children having pre-vaccination anti VZV IgG titer <10 mIU/mL (< 5 gp ELISA units/mL) were 80% for Bio Pox™ and 77% for Varivax™ (p = 0.692). The seroconversion rate in the group receiving Bio Pox™ was non-inferior to the group that received Varivax™. There were mild local reactions for both the vaccines; none of the patient had fever or required hospitalization or medication. The Bio Pox™ was found to be safe and immunogenic in children against VZV infection.

  1. Phase I-II trial of oral cyclophosphamide, prednisone and lenalidomide for the treatment of patients with relapsed and refractory multiple myeloma.

    Science.gov (United States)

    Reece, Donna E; Masih-Khan, Esther; Atenafu, Eshetu G; Jimenez-Zepeda, Victor H; Anglin, Peter; Chen, Christine; Kukreti, Vishal; Mikhael, Joseph R; Trudel, Suzanne

    2015-01-01

    This single institution, open label Phase I-II dose escalation trial evaluated the safety and efficacy of the combination of lenalidomide (Revlimid®), cyclophosphamide and prednisone (CPR) in patients with relapsed/refractory multiple myeloma. The maximal administered dose of CPR consisted of cyclophosphamide 300 mg/m(2) on day 1, 8, and 15, lenalidomide 25 mg on d 1-21 and prednisone 100 mg every other day in a 28-d cycle. Between November 2007 and June 2009, 32 patients were entered in cohorts of three at three dose levels. The median age was 64 years, 59% were male, with a median two prior regimens. Responding patients could stay on treatment until progression. The full-dose CPR regimen produced no dose-limiting toxicity and was delivered for a median of 16 months (3·5-65 months) with acceptable safety and tolerance. The overall response rate (≥ partial response) was 94% at a median follow up of 28 months. The median progression-free survival was 16·1 months [95% confidence interval (CI); 10·9-22·5 months], while the median overall survival was 27·6 months (95% CI; 16·8-36·6 months). Only the beta-2 microglobulin level at protocol entry correlated with a better survival (P = 0·047). These observations compare favourably with other 2- and 3- drug combinations for relapsed/refractory myeloma, and suggest that CPR should be evaluated further in the setting of relapsed/refractory disease, or in newly diagnosed patients.

  2. Lanreotide Autogel 90 mg and lymphorrhea prevention after axillary node dissection in breast cancer: a phase III double blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Gauthier, T; Garuchet-Bigot, A; Marin, B; Mollard, J; Loum, O; Fermeaux, V; Jammet, I; Kanoun, D; Maubon, A; Aubard, Y

    2012-10-01

    The aim of this study was to assess the efficacy of Lanreotide Autogel 90 mg PR to prevent lymphorrhea after axillary dissection in breast cancer. A Phase III double-blind, randomized, placebo-controlled trial was performed between April 1st, 2008, and December 31st, 2010. The primary endpoint was the lymphorrhea volume (ml) in the axillary drain during the first four postoperative days. The secondary end points were the number of days until axillary drain removal, hospital stay duration (days), lymphorrhea volume (ml) up to days 15, 30 and 180, number of cases with seroma aspiration and number of seroma aspirations, evaluation of wound, arm pain and mobility on days 15, 30 and 180. A total of 148 patients were recruited for the study. Altogether 145 patients were randomized and analysed on an intention-to-treat basis. On the day before surgery 73 patients received the placebo and 72 patients received lanreotide. At four postoperative days, there was a tendency towards a reduction of the lymphorrhea volume in the lanreotide group (median 292 ml, range 1-965 ml) as compared to the placebo group (median 337 ml, range 0-1230 ml), although it was not statistically significant (p = 0.18). There was no significant difference for the secondary end points. In the group with axillary dissection performed alone (n = 24), the lymphorrhea volume was shown to be significantly reduced in the lanreotide group, (p = 0.035) as compared to the placebo group. Our study did not identify any overall significant reduction of lymphorrhea on lanreotide. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Efficacy of lanreotide Autogel® administered every 4–8 weeks in patients with acromegaly previously responsive to lanreotide microparticles 30 mg: a phase III trial

    Science.gov (United States)

    Lucas, T; Astorga, R

    2006-01-01

    Objective and design Depot somatostatin analogues are well accepted as either adjuvant or primary therapy for acromegaly, and their long dosage intervals facilitate adherence to treatment. Our objective was to evaluate whether lanreotide Autogel® 120 mg, every 4–8 weeks, was as effective in controlling acromegaly as lanreotide microparticles 30 mg, every 1–2 weeks. Patients design and measurements Patients who had used lanreotide microparticles 30 mg, ≥ 2 months prestudy, and had responded to treatment were recruited to this open, prospective, multicentre phase III trial. Three to five injections of lanreotide Autogel® 120 mg were administered. Lanreotide Autogel® 120 mg was injected every 4, 6 or 8 weeks in patients previously receiving lanreotide microparticles every 7, 10 or 14 days, respectively. GH and insulin-like growth factor (IGF)-1 levels were assessed one dosing interval after the final injections. Results Ninety-eight patients were enrolled and 93 completed. Steady-state GH concentrations demonstrated similar efficacy between the formulations (upper 95% confidence interval of the quotient, 77·7%). Mean (SE) GH levels were lower with lanreotide Autogel® than with lanreotide microparticles (3·8 (0·5) vs 4·3 (0·5) ng/ml; P < 0·001). GH levels < 2·5 ng/ml were observed in 54% and 46% of patients; 40% and 35% having GH < 2·5 ng/ml and normalized IGF-1 with lanreotide Autogel® and microparticles, respectively. Symptoms were controlled better with lanreotide Autogel® and treatment was well accepted. Conclusions Lanreotide Autogel® 120 mg every 4–8 weeks, is at least as effective and as well tolerated in acromegaly as lanreotide microparticles 30 mg injected every 7–14 days. PMID:16918950

  4. P13, the EMBL macromolecular crystallography beamline at the low-emittance PETRA III ring for high- and low-energy phasing with variable beam focusing

    Science.gov (United States)

    Cianci, Michele; Bourenkov, Gleb; Pompidor, Guillaume; Karpics, Ivars; Kallio, Johanna; Bento, Isabel; Roessle, Manfred; Cipriani, Florent; Fiedler, Stefan; Schneider, Thomas R.

    2017-01-01

    The macromolecular crystallography P13 beamline is part of the European Molecular Biology Laboratory Integrated Facility for Structural Biology at PETRA III (DESY, Hamburg, Germany) and has been in user operation since mid-2013. P13 is tunable across the energy range from 4 to 17.5 keV to support crystallographic data acquisition exploiting a wide range of elemental absorption edges for experimental phase determination. An adaptive Kirk­patrick–Baez focusing system provides an X-ray beam with a high photon flux and tunable focus size to adapt to diverse experimental situations. Data collections at energies as low as 4 keV (λ = 3.1 Å) are possible due to a beamline design minimizing background and maximizing photon flux particularly at low energy (up to 1011 photons s−1 at 4 keV), a custom calibration of the PILATUS 6M-F detector for use at low energies, and the availability of a helium path. At high energies, the high photon flux (5.4 × 1011 photons s−1 at 17.5 keV) combined with a large area detector mounted on a 2θ arm allows data collection to sub-atomic resolution (0.55 Å). A peak flux of about 8.0 × 1012 photons s−1 is reached at 11 keV. Automated sample mounting is available by means of the robotic sample changer ‘MARVIN’ with a dewar capacity of 160 samples. In close proximity to the beamline, laboratories have been set up for sample preparation and characterization; a laboratory specifically equipped for on-site heavy atom derivatization with a library of more than 150 compounds is available to beamline users. PMID:28009574

  5. Directed shift of vaginal flora after topical application of sucrose gel in a phase III clinical trial: a novel treatment for bacterial vaginosis.

    Science.gov (United States)

    Zeng, Zhong-ming; Liao, Qin-pin; Yao, Chen; Geng, Li; Feng, Li-hua; Shi, Hui-rong; Xin, Xiao-yan; Li, Ping; Wang, Hui-lan; Pang, Yi-cun; Liu, Shu-wen; Jiang, Shi-bo

    2010-08-05

    Bacterial vaginosis (BV) is one of the most common infectious diseases among sexually active women and is associated with the increased acquisition of a variety of sexually transmitted diseases. This study aimed to compare the efficacy of a non-antibiotic sucrose gel against an antibiotic metronidazole gel for the treatment of BV. A randomized, double-blinded, multi-center, parallel-group, placebo-controlled phase III clinical trial was conducted at eight hospitals in China. A total of 560 subjects with clinically diagnosed BV were randomly assigned into three groups for vaginally receiving sucrose, metronidazole, and placebo gels, respectively, twice daily for five consecutive days. The efficacy of therapeutic cure, defined as an achievement of both microbiologic cure (a Nugent score of 3 or less) and clinical cure (a resolution of the clinical findings from the baseline visit), was evaluated at the 1st and 2nd test-of-cure (TOC) visits at 7-10 and 21-35 days after the start of treatment, respectively. Therapeutic cure rates for sucrose, metronidazole, and placebo gel groups were 83.13%, 71.30% and 0.92%, at the 1st TOC, and 61.04%, 66.67% and 7.34%, at the 2nd TOC, respectively. While there was no significant difference between the sucrose and metronidazole gel groups at the 2nd TOC (P = 0.305), and sucrose gel was more effective than metronidazole gel at the 1st TOC (P = 0.009). These findings suggest that sucrose gel restores normal vaginal flora more rapidly than metronidazole gel and can be used as a novel treatment for BV.

  6. Continuous 7-Days-A-Week External Beam Irradiation in Locally Advanced Cervical Cancer: Final Results of the Phase I/II Study

    Energy Technology Data Exchange (ETDEWEB)

    Serkies, Krystyna, E-mail: kserkies@wp.pl [Department of Oncology and Radiotherapy, Medical University of Gdansk (Poland); Dziadziuszko, Rafal; Jassem, Jacek [Department of Oncology and Radiotherapy, Medical University of Gdansk (Poland)

    2012-03-01

    Purpose: To evaluate the feasibility and efficacy of definitive continuous 7-days-a-week pelvic irradiation without breaks between external beam radiotherapy and brachytherapy in locally advanced cervical cancer. Methods and Materials: Between November 1998 and December 1999, 30 patients with International Federation of Obstetrics and Gynecology Stage IIB or IIIB cervical cancer were included in a prospective Phase I/II study of continuous 7-days-a-week pelvic irradiation, to the total Manchester point B dose of 40.0-57.6 Gy. The first 13 patients (Group A) were given a daily tumor dose of 1.6 Gy, and the remaining 17 patients (Group B) were given 1.8 Gy. One or two immediate brachytherapy applications (point A dose 10-20 Gy, each) were performed in 28 cases. Results: Two patients did not complete the irradiation because of apparent early progression of disease during the irradiation. Eleven of the 28 evaluable patients (39%; 45% and 35% in Groups A and B, respectively) completed their treatment within the prescribed overall treatment time. Acute toxicity (including severe European Organisation for Research and Treatment of Cancer/Radiation Therapy Oncology Group Grade 3 and 4 effects in 40%) was experienced by 83% of patients and resulted in unplanned treatment interruptions in 40% of all patients (31% and 47% of patients in Groups A and B, respectively). Severe intestinal side effects occurred in 31% and 41% of Patients in Groups A and B, respectively (p = 0.71). The 5-year overall survival probability was 33%. Cancer recurrence occurred in 63% of patients: 20% inside and 57% outside the pelvis. Cumulative incidence of late severe bowel and urinary bladder toxicity at 24 months was 15%. Conclusion: Continuous irradiation in locally advanced cervical cancer is associated with a high incidence of severe acute toxicity, resulting in unplanned treatment interruptions. Late severe effects and survival after continuous radiotherapy do not substantially differ from

  7. Silver Clear Nylon Dressing is Effective in Preventing Radiation-Induced Dermatitis in Patients With Lower Gastrointestinal Cancer: Results From a Phase III Study

    Energy Technology Data Exchange (ETDEWEB)

    Niazi, Tamim M. [Segal Cancer Centre, Department of Radiation Oncology, Jewish General Hospital, McGill University (Canada); Vuong, Te, E-mail: tvuong@jgh.mcgill.ca [Segal Cancer Centre, Department of Radiation Oncology, Jewish General Hospital, McGill University (Canada); Azoulay, Laurant [Department of Epidemiology, Jewish General Hospital, McGill University (Canada); Marijnen, Corrie [Department of Clinical Oncology, Leiden University Medical Center, Amsterdam (Netherlands); Bujko, Kryzstof [Department of Radiotherapy, The Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw (Poland); Nasr, Elie [Department of Radiation Oncology, Hotel-Dieu de France Hospital (Lebanon); Lambert, Christine; Duclos, Marie; Faria, Sergio; David, Marc [Department of Radiation Oncology, Montreal-General-Hospital, McGill University, Montreal (Canada); Cummings, Bernard [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto (Canada)

    2012-11-01

    Purpose: For patients with anal canal and advanced rectal cancer, chemoradiation therapy is a curative modality or an important adjunct to surgery. Nearly all patients treated with chemoradiation experience some degree of radiation-induced dermatitis (RID). Prevention and effective treatment of RID, therefore, is of considerable clinical relevance. The present phase III randomized trial compared the efficacy of silver clear nylon dressing (SCND) with that of standard skin care for these patients. Methods and Materials: A total of 42 rectal or anal canal cancer patients were randomized to either a SCND or standard skin care group. SCND was applied from Day 1 of radiation therapy (RT) until 2 weeks after treatment completion. In the control arm, sulfadiazine cream was applied at the time of skin dermatitis. Printed digital photographs taken 2 weeks prior to, on the last day, and two weeks after the treatment completion were scored by 10 blinded readers, who used the common toxicity scoring system for skin dermatitis. Results: The radiation dose ranged from 50.4 to 59.4 Gy, and there were no differences between the 2 groups. On the last day of RT, when the most severe RID occurs, the mean dermatitis score was 2.53 (standard deviation [SD], 1.17) for the standard and 1.67 (SD, 1.2; P=.01) for the SCND arm. At 2 weeks after RT, the difference was 0.39 points in favor of SCND (P=.39). There was considerable intraclass correlation among the 10 observers. Conclusions: Silver clear nylon dressing is effective in reducing RID in patients with lower gastrointestinal cancer treated with combined chemotherapy and radiation treatment.

  8. Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer

    Directory of Open Access Journals (Sweden)

    Davidson Neville

    2004-07-01

    Full Text Available Abstract Background This multicentre phase I/II study was designed to determine the maximum tolerated dose of irinotecan when combined with 5-fluorouracil and folinic acid according to the Mayo Clinic schedule and to evaluate the activity of this combination as first-line therapy in patients with advanced colorectal cancer. Methods Sixty-three patients received irinotecan (250 or 300 mg/m2, 30- to 90-minute intravenous infusion on day 1, immediately followed by folinic acid (20 mg/m2/day and 5-fluorouracil (425 mg/m2, 15-minute bolus infusion days 1 to 5, every four weeks. Results Diarrhoea was dose limiting at 300 mg/m2 irinotecan in combination with 5-fluorouracil and folinic acid, and this was determined to be the maximum tolerated dose. Grade 3–4 neutropenia was the most frequently reported toxicity. The recommended dose of irinotecan for the phase II part of the study was 250 mg/m2. The response rate for the evaluable patient population was 36% (13/36, and 44% (16 patients had stable disease (including 19% of minor response. For the intention-to-treat population, the response rate was 29% (14/49 and 35% (17 patients stable disease (including 14% of minor response. The median time to progression was 7.0 months and the median survival was 12.0 months. Grade 3–4 non-haematological drug-related toxicities included delayed diarrhoea, stomatitis, fatigue, and nausea/vomiting. There were three deaths due to septic shock that were possibly or probably treatment-related. Conclusions This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus 5-fluorouracil/folinic acid every four weeks showed activity as first-line therapy in patients with advanced colorectal cancer. In keeping with other published results of studies using bolus 5-fluorouracil combined with irinotecan, the use of this regimen is limited by a relatively high rate of grade 3–4 neutropenia, and the combination of irinotecan and infusional 5-fluorouracil

  9. Increasing subject compliance in pivotal phase III clinical trials of dolutegravir (DTG, S/GSK1349572 in HIV-infected, ART-naïve subjects

    Directory of Open Access Journals (Sweden)

    J Harris

    2012-11-01

    Full Text Available To maximise the application of results of large-scale clinical trials, recruitment and retention of a diverse subject population is key. With commonly used algorithms (Snapshot, TLOVR, missing = failure, all withdrawals in HIV studies, regardless of reason, are classed as failures in efficacy analyses. Good subject compliance therefore improves statistical power and the quality of trial results. In four recent GSK/ViiV-sponsored phase IIIB/IV HIV ART-naïve studies (HEAT, KLEAN, APV109141 and ARIES, 24% of subjects withdrew and approximately 2/3 of these withdrawals (16% potentially were avoidable (i.e. not treatment related [1]. To increase subject compliance in the phase III, treatment-naïve studies of DTG (ING113086 “SPRING-2” and ING114467 “SINGLE”, a more robust subject compliance program focussing on understanding subject needs and building sponsor-site and site-subject relationships was implemented. The compliance program included opt-in study visit reminders, late study visit tracking, subject compliance support materials, subject transportation support, on-going site training, relationship management and presentations on prior withdrawal rates and associated risk factors for attrition at investigator meetings. Week 48 withdrawals, both overall and for potentially avoidable reasons, were considerably lower in SPRING-2 and SINGLE than historical HIV trials. Comparison of withdrawal rates prior to, and after implementation of robust patient compliance program. Addressing individual study subject needs with a customized approach in SPRING-2 and SINGLE contributed to considerably lower percentages of withdrawals than in historical HIV studies. Identifying the specific impact of a single subject compliance initiative is difficult as study compliance can be influenced by overall study design, investigational product tolerability profile, current standard of care and treatment access for the disease under study. However, consistently

  10. Solid-phase extraction of Fe(III), Pb(II) and Cr(III) in environmental samples on amberlite XAD-7 and their determinations by flame atomic absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Divrikli, Umit [Pamukkale University, Faculty of Arts and Science, Department of Chemistry, Denizli 20020 (Turkey)], E-mail: udivrikli@pamukkale.edu.tr; Akdogan, Abdullah [Pamukkale University, Faculty of Arts and Science, Department of Chemistry, Denizli 20020 (Turkey); Soylak, Mustafa [Erciyes University, Faculty of Arts and Science, Department of Chemistry, Kayseri 38039 (Turkey); Elci, Latif [Pamukkale University, Faculty of Arts and Science, Department of Chemistry, Denizli 20020 (Turkey)

    2007-10-22

    This paper describes a simple and accurate procedure for preconcentration of trace amounts of Fe(III), Pb(II) and Cr(III) ions. The preconcentration procedure is based on retention of p-xylenol blue chelates on Amberlite XAD-7. The analytes retained were eluted from Amberlite XAD-7 by using 1 mol L{sup -1} HCl. The influences of the analytical parameters including amounts of reagents, pH and type of eluent were also investigated. The detection limits of Fe, Pb and Cr were found to be 3.07, 18.6 and 3.27 {mu}g L{sup -1}, respectively. The accuracy of the procedure was checked by the analysis of an electrolytic copper wire sample. The relative error was less than 5%. The presented method was applied to the determination of Fe(III), Pb(II) and Cr(III) in water samples from Denizli, Turkey with good results such as recoveries more than 95%, relative standard deviations below 10%.

  11. Solid-phase extraction of Fe(III), Pb(II) and Cr(III) in environmental samples on amberlite XAD-7 and their determinations by flame atomic absorption spectrometry.

    Science.gov (United States)

    Divrikli, Umit; Akdogan, Abdullah; Soylak, Mustafa; Elci, Latif

    2007-10-22

    This paper describes a simple and accurate procedure for preconcentration of trace amounts of Fe(III), Pb(II) and Cr(III) ions. The preconcentration procedure is based on retention of p-xylenol blue chelates on Amberlite XAD-7. The analytes retained were eluted from Amberlite XAD-7 by using 1 mol L(-1) HCl. The influences of the analytical parameters including amounts of reagents, pH and type of eluent were also investigated. The detection limits of Fe, Pb and Cr were found to be 3.07, 18.6 and 3.27 microg L(-1), respectively. The accuracy of the procedure was checked by the analysis of an electrolytic copper wire sample. The relative error was less than 5%. The presented method was applied to the determination of Fe(III), Pb(II) and Cr(III) in water samples from Denizli, Turkey with good results such as recoveries more than 95%, relative standard deviations below 10%.

  12. Both Phosphorus Fertilizers and Indigenous Bacteria Enhance Arsenic Release into Groundwater in Arsenic-Contaminated Aquifers.

    Science.gov (United States)

    Lin, Tzu-Yu; Wei, Chia-Cheng; Huang, Chi-Wei; Chang, Chun-Han; Hsu, Fu-Lan; Liao, Vivian Hsiu-Chuan

    2016-03-23

    Arsenic (As) is a human carcinogen, and arsenic contamination in groundwater is a worldwide public health concern. Arsenic-affected areas are found in many places but are reported mostly in agricultural farmlands, yet the interaction of fertilizers, microorganisms, and arsenic mobilization in arsenic-contaminated aquifers remains uncharacterized. This study investigates the effects of fertilizers and bacteria on the mobilization of arsenic in two arsenic-contaminated aquifers. We performed microcosm experiments using arsenic-contaminated sediments and amended with inorganic nitrogenous or phosphorus fertilizers for 1 and 4 months under aerobic and anaerobic conditions. The results show that microcosms amended with 100 mg/L phosphorus fertilizers (dipotassium phosphate), but not nitrogenous fertilizers (ammonium sulfate), significantly increase aqueous As(III) release in arsenic-contaminated sediments under anaerobic condition. We also show that concentrations of iron, manganese, potassium, sodium, calcium, and magnesium are increased in the aqueous phase and that the addition of dipotassium phosphate causes a further increase in aqueous iron, potassium, and sodium, suggesting that multiple metal elements may take part in the arsenic release process. Furthermore, microbial analysis indicates that the dominant microbial phylum is shifted from α-proteobacteria to β- and γ-proteobacteria when the As(III) is increased and phosphate is added in the aquifer. Our results provide evidence that both phosphorus fertilizers and microorganisms can mediate the release of arsenic to groundwater in arsenic-contaminated sediments under anaerobic condition. Our study suggests that agricultural activity such as the use of fertilizers and monitoring phosphate concentration in groundwater should be taken into consideration for the management of arsenic in groundwater.

  13. Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC).

    Science.gov (United States)

    Pearce, Neil; Aït-Khaled, Nadia; Beasley, Richard; Mallol, Javier; Keil, Ulrich; Mitchell, Ed; Robertson, Colin

    2007-09-01

    Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC) was designed to allow worldwide comparisons of the prevalence of asthma symptoms. In phase III the phase I survey was repeated in order to assess changes over time. The phase I survey was repeated after an interval of 5-10 years in 106 centres in 56 countries in children aged 13-14 years (n = 304,679) and in 66 centres in 37 countries in children aged 6-7 years (n = 193,404). The mean symptom prevalence of current wheeze in the last 12 months changed slightly from 13.2% to 13.7% in the 13-14 year age group (mean increase of 0.06% per year) and from 11.1% to 11.6% in the 6-7 year age group (mean increase of 0.13% per year). There was also little change in the mean symptom prevalence of severe asthma or the symptom prevalence measured with the asthma video questionnaire. However, the time trends in asthma symptom prevalence showed different regional patterns. In Western Europe, current wheeze decreased by 0.07% per year in children aged 13-14 years but increased by 0.20% per year in children aged 6-7 years. The corresponding findings per year for the other regions in children aged 13-14 years and 6-7 years, respectively, were: Oceania (-0.39% and -0.21%); Latin America (+0.32% and +0.07%); Northern and Eastern Europe (+0.26% and +0.05%); Africa (+0.16% and +0.10%); North America (+0.12% and +0.32%); Eastern Mediterranean (-0.10% and +0.79%); Asia-Pacific (+0.07% and -0.06%); and the Indian subcontinent (+0.02% and +0.06%). There was a particularly marked reduction in current asthma symptom prevalence in English language countries (-0.51% and -0.09%). Similar patterns were observed for symptoms of severe asthma. However, the percentage of children reported to have had asthma at some time in their lives increased by 0.28% per year in the 13-14 year age group and by 0.18% per year in the 6-7 year age group. These findings indicate that international differences in asthma symptom prevalence

  14. Phase II Contaminant Transport Parameters for the Groundwater Flow and Contaminant Transport Model of Corrective Action Unit 98: Frenchman Flat, Nye County, Nevada, Rev. No.: 0

    Energy Technology Data Exchange (ETDEWEB)

    DeNovio, Nicole M.; Bryant, Nathan; King, Chrissi B.; Bhark, Eric; Drellack, Sigmund L.; Pickens, John F.; Farnham, Irene; Brooks, Keely M.; Reimus, Paul; Aly, Alaa

    2005-04-01

    This report documents pertinent transport data and data analyses as part of the Phase II Corrective Action Investigation (CAI) for Frenchman Flat (FF) Corrective Action Unit (CAU) 98. The purpose of this data compilation and related analyses is to provide the primary reference to support parameterization of the Phase II FF CAU transport model.

  15. Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part).

    Science.gov (United States)

    Vermorken, J B; Peyrade, F; Krauss, J; Mesía, R; Remenar, E; Gauler, T C; Keilholz, U; Delord, J P; Schafhausen, P; Erfán, J; Brümmendorf, T H; Iglesias, L; Bethe, U; Hicking, C; Clement, P M

    2014-03-01

    Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy. The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN. The phase II part reported here was an open-label, randomized, controlled trial investigating progression-free survival (PFS). Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease progression or unacceptable toxicity. One hundred and eighty-two patients were treated. Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). Accordingly, median overall survival and objective response rates were not improved with cilengitide (12.4 months/47%, 10.6 months/27%, and 11.6 months/36%, respectively). No clinically meaningful safety differences were observed between groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67, vascular endothelial growth factor receptor 2, vascular endothelial-cadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus) were predictive of outcome. Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M-SCCHN patients.

  16. Spectral Induced Polarization monitoring of the groundwater physico-chemical parameters daily variations for stream-groundwater interactions

    Science.gov (United States)

    Jougnot, Damien; Camerlynck, Christian; Robain, Henri; Tallec, Gaëlle; Ribolzi, Olivier; Gaillardet, Jérôme

    2017-04-01

    During the last decades, geophysical methods have been attracting an increasing interest in hydrology and environmental sciences given their sensitivity to parameters of interests and their non-intrusive nature. The Spectral Induced Polarization (SIP) is a low frequency electro-magnetic method that allows the characterization of the subsurface through its complex electrical conductivity. It reports the modulus of the conductivity and the phase between an injected current and a measured voltage over a rather large frequency range (from few millihertz to few tens of kilohertz). The real part of the conductivity is sensitive to lithological (porosity, specific surface area) and hydrological (water saturation, water salinity) parameters, while the imaginary part is linked to electrochemical polarizations, that have been shown to be largely influenced by the chemistry of the pore water. In the present contribution, we aim at better characterizing the exchanges between a stream and the surrounding groundwater using the SIP method and its sensitivity to pore water changes over time. Two sites from the OZCAR Research Infrastructure (French Critical Zone observatories) have been chosen for this study: the Houay Pano catchment (Laos) and the Orgeval catchment (France). These two sites have a good existing infrastructure and have been already studied extensively in terms of hydrology, geophysics, and hydrochemistry. They constitute perfect experimental sites to develop novel methodologies for the assessment of stream-groundwater exchanges. We propose to obtain a vertical description of the changes in complex electrical conductivity with depth based on SIP soundings undertaken with the multi-channel system SIP Fuchs III. We conducted a high-frequency monitoring close to a river stream (one vertical profiles every 30 min). In parallel, a high frequency monitoring of the physico-chemical parameters (temperature, conductivity, ionic concentrations) in the river stream has been

  17. Uptake Mechanisms of Eu(III) on Hydroxyapatite: A Potential Permeable Reactive Barrier Backfill Material for Trapping Trivalent Minor Actinides.

    Science.gov (United States)

    Xu, Lin; Zheng, Tao; Yang, Shitong; Zhang, Linjuan; Wang, Jianqiang; Liu, Wei; Chen, Lanhua; Diwu, Juan; Chai, Zhifang; Wang, Shuao

    2016-04-05

    The permeable reactive barrier (PRB) technique has attracted an increasing level of attention for the in situ remediation of contaminated groundwater. In this study, the macroscopic uptake behaviors and microscopic speciation of Eu(III) on hydroxyapatite (HAP) were investigated by a combination of theoretical modeling, batch experiments, powder X-ray diffraction (PXRD) fitting, and X-ray absorption spectroscopy (XAS). The underlying removal mechanisms were identified to further assess the application potential of HAP as an effective PRB backfill material. The macroscopic analysis revealed that nearly all dissolved Eu(III) in solution was removed at pH 6.5 within an extremely short reaction time of 5 min. In addition, the thermodynamic calculations, desorption experiments, and PXRD and XAS analyses definitely confirmed the formation of the EuPO4·H2O(s) phase during the process of uptake of dissolved Eu(III) by HAP via the dissolution-precipitation mechanism. A detailed comparison of the present experimental findings and related HAP-metal systems suggests that the relative contribution of precipitation to the total Eu(III) removal increases as the P:Eu ratio decreases. The dosage of HAP-based PRB for the remediation of groundwater polluted by Eu(III) and analogous trivalent actinides [e.g., Am(III) and Cm(III)] should be strictly controlled depending on the dissolved Eu(III) concentration to obtain an optimal P:M (M represents Eu, Am, or Cm) ratio and treatment efficiency.

  18. TRIO-012: a multicenter, multinational, randomized, double-blind phase III study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer.

    Science.gov (United States)

    Mackey, John; Gelmon, Karen; Martin, Miguel; McCarthy, Nicole; Pinter, Tamas; Rupin, Mathieu; Youssoufian, Hagop

    2009-11-01

    In this multinational, placebo-controlled, randomized phase III trial, Translational Research In Oncology (TRIO) will define the efficacy and safety of adding a novel antiangiogenic agent, IMC-1121B (ramucirumab), to standard first-line docetaxel chemotherapy for women with HER2-negative metastatic breast cancer. We will evaluate whether the addition of IMC-1121B prolongs progression-free survival and whether its use improves overall survival. Accrual is under way.

  19. Randomised phase III study of biweekly 24-h infusion of high-dose 5FU with folinic acid and oxaliplatin versus monthly plus 5-FU/folinic acid in first-line treatment of advanced colorectal cancer

    NARCIS (Netherlands)

    Hospers, GAP; Schaapveld, M; Nortier, JWR; Wils, J; van Bochove, A; de Jong, RS; Creemers, GJ; Erjavec, Z; de Gooyer, DJ; Slee, PHTJ; Gerrits, CJH; Smit, J.M.; Mulder, NH

    2006-01-01

    Background: A phase III study was started to compare oxaliplatin/5FU/LV in the first-line with bolus FU/LV in metastatic colorectal cancer. Patients and methods: 302 patients were randomised and received bolus 5-FU 425 mg/m(2) day 1-5, FA 20 mg/m(2) day 1-5, q 4 wk or oxaliplatin 85 mg/m(2), 2 h-inf

  20. 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 to ge...... GD compared with docetaxel demonstrated increased TTP in metastatic breast cancer. However, RR and OS were similar. Thus, the addition of gemcitabine failed to demonstrate any clinically meaningful benefit when combined with docetaxel....

  1. Influence of Wetting and Mass Transfer Properties of Organic Chemical Mixtures in Vadose Zone Materials on Groundwater Contamination by Nonaqueous Phase Liquids

    Energy Technology Data Exchange (ETDEWEB)

    Charles J Werth; Albert J Valocchi, Hongkyu Yoon

    2011-05-21

    Previous studies have found that organic acids, organic bases, and detergent-like chemicals change surface wettability. The wastewater and NAPL mixtures discharged at the Hanford site contain such chemicals, and their proportions likely change over time due to reaction-facilitated aging. The specific objectives of this work were to (1) determine the effect of organic chemical mixtures on surface wettability, (2) determine the effect of organic chemical mixtures on CCl4 volatilization rates from NAPL, and (3) accurately determine the migration, entrapment, and volatilization of organic chemical mixtures. Five tasks were proposed to achieve the project objectives. These are to (1) prepare representative batches of fresh and aged NAPL-wastewater mixtures, (2) to measure interfacial tension, contact angle, and capillary pressure-saturation profiles for the same mixtures, (3) to measure interphase mass transfer rates for the same mixtures using micromodels, (4) to measure multiphase flow and interphase mass transfer in large flow cell experiments, all using the same mixtures, and (5) to modify the multiphase flow simulator STOMP in order to account for updated P-S and interphase mass transfer relationships, and to simulate the impact of CCl4 in the vadose zone on groundwater contamination. Results and findings from these tasks and summarized in the attached final report.

  2. Field Test Report: Preliminary Aquifer Test Characterization Results for Well 299-W15-225: Supporting Phase I of the 200-ZP-1 Groundwater Operable Unit Remedial Design

    Energy Technology Data Exchange (ETDEWEB)

    Spane, Frank A.; Newcomer, Darrell R.

    2009-09-23

    This report examines the hydrologic test results for both local vertical profile characterization and large-scale hydrologic tests associated with a new extraction well (well 299-W15-225) that was constructed during FY2009 for inclusion within the future 200-West Area Groundwater Treatment System that is scheduled to go on-line at the end of FY2011. To facilitate the analysis of the large-scale hydrologic test performed at newly constructed extraction well 299-W15-225 (C7017; also referred to as EW-1 in some planning documents), the existing 200-ZP-1 interim pump-and-treat system was completely shut-down ~1 month before the performance of the large-scale hydrologic test. Specifically, this report 1) applies recently developed methods for removing barometric pressure fluctuations from well water-level measurements to enhance the detection of hydrologic test and pump-and-treat system effects at selected monitor wells, 2) analyzes the barometric-corrected well water-level responses for a preliminary determination of large-scale hydraulic properties, and 3) provides an assessment of the vertical distribution of hydraulic conductivity in the vicinity of newly constructed extraction well 299-W15-225. The hydrologic characterization approach presented in this report is expected to have universal application for meeting the characterization needs at other remedial action sites located within unconfined and confined aquifer systems.

  3. Adsorptive removal of manganese, arsenic and iron from groundwater

    NARCIS (Netherlands)

    Buamah, R.

    2009-01-01

    To determine the scale of the problem of arsenic, iron and manganese contamination of groundwater in Ghana a survey was performed in the first phase of the research to provide in depth information with respect to these contaminants. Presence of these mentioned contaminants in groundwater is not pecu

  4. Adsorptive removal of manganese, arsenic and iron from groundwater

    NARCIS (Netherlands)

    Buamah, R.

    2009-01-01

    To determine the scale of the problem of arsenic, iron and manganese contamination of groundwater in Ghana a survey was performed in the first phase of the research to provide in depth information with respect to these contaminants. Presence of these mentioned contaminants in groundwater is not

  5. Effect of Secukinumab on Patient‐Reported Outcomes in Patients With Active Ankylosing Spondylitis: A Phase III Randomized Trial (MEASURE 1)

    Science.gov (United States)

    Dougados, Maxime; Baeten, Dominique L.; Cheng‐Chung Wei, James; Geusens, Piet; Readie, Aimee; Richards, Hanno B.; Martin, Ruvie; Porter, Brian

    2016-01-01

    Objective To evaluate the effect of secukinumab (interleukin‐17A inhibitor) on patient‐reported outcomes in patients with active ankylosing spondylitis (AS). Methods In this phase III study, 371 patients were randomized (1:1:1) to receive intravenous (IV) secukinumab 10 mg/kg at baseline and weeks 2 and 4 followed by subcutaneous (SC) secukinumab 150 mg every 4 weeks (IV→150 mg group), or SC secukinumab 75 mg every 4 weeks (IV→75 mg group), or placebo. Patient‐reported outcomes included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI criteria for 50% improvement (BASDAI 50), Short Form 36 (SF‐36) physical component summary (PCS) score and mental component summary (MCS) score, Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, Bath Ankylosing Spondylitis Functional Index (BASFI), EuroQol 5‐domain (EQ‐5D) questionnaire, Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐F), and Work Productivity and Activity Impairment–General Health questionnaire (WPAI‐GH). Results At week 16, secukinumab IV→150 mg or IV→75 mg was associated with statistically and clinically significant improvements from baseline versus placebo in the BASDAI (−2.3 for both regimens versus −0.6; P < 0.0001 and P < 0.001, respectively), SF‐36 PCS (5.6 for both regimens versus 1.0; P < 0.0001 and P < 0.001, respectively), and ASQoL (−3.6 for both regimens versus −1.0; P < 0.0001 and P < 0.001, respectively). Clinically significant improvements in the SF‐36 MCS, BASFI, EQ‐5D, and BASDAI 50 were observed with both secukinumab groups versus placebo at week 16; improvements were also observed in the FACIT‐F and WPAI‐GH. All improvements were sustained through week 52. Conclusion Our findings indicate that secukinumab provides significant and sustained improvements in patient‐reported disease activity and health‐related quality of life, and reduces functional impairment, fatigue, and

  6. Effect of Secukinumab on Patient-Reported Outcomes in Patients With Active Ankylosing Spondylitis: A Phase III Randomized Trial (MEASURE 1).

    Science.gov (United States)

    Deodhar, Atul A; Dougados, Maxime; Baeten, Dominique L; Cheng-Chung Wei, James; Geusens, Piet; Readie, Aimee; Richards, Hanno B; Martin, Ruvie; Porter, Brian

    2016-12-01

    To evaluate the effect of secukinumab (interleukin-17A inhibitor) on patient-reported outcomes in patients with active ankylosing spondylitis (AS). In this phase III study, 371 patients were randomized (1:1:1) to receive intravenous (IV) secukinumab 10 mg/kg at baseline and weeks 2 and 4 followed by subcutaneous (SC) secukinumab 150 mg every 4 weeks (IV→150 mg group), or SC secukinumab 75 mg every 4 weeks (IV→75 mg group), or placebo. Patient-reported outcomes included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI criteria for 50% improvement (BASDAI 50), Short Form 36 (SF-36) p