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Sample records for rica phase iii

  1. District Practices Study. Phase III Summary Report.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    Following up on the first two phases (1976-82) of the "District Practices Study" of Title I of the Elementary and Secondary Education Act (ESEA) as presented in a resource book and seven special reports, this report is devoted to the study's third and final phase. During phase III (1982-83), researchers visited 14 sites to describe their solutions…

  2. DHS Phase III activities underway.

    PubMed

    1993-01-01

    Activities and improvements in the third round of the Demographic and Health Surveys (DHS) are described for the first year of the five year DHS-III project during 1992-97. Underway are data quality assessments, identification of data needs, development of a new core questionnaire and modules, and fieldwork survey implementation. Data quality studies are conducted on respondent age, age at first marriage, birth history, knowledge and use of contraception, and health of children aged under 5 years. An analysis of reinterview subsamples for Pakistan and Nigeria will test reliability of data. Emerging data needs for the decade are identified through consultations with data users in the population and health fields. A variety of organizational representatives and recognized experts provide valuable inputs on questionnaire content and module topics. This article also reveals that a shorter questionnaire length will be considered. There will be new questionnaire topics on reliance on breast feeding for contraception, induced abortion and complications, and quality of care. Reductions are made in little used data and retrospective data longer than 3-5 years preceding the survey date. Revisions are made in the Interviewer's and Supervisor's Manuals, the Service Availability Questionnaire, the Male/Husbands Questionnaire, and fifteen modules. Fieldwork is either in progress of completion in Ghana, Kenya, the Philippines, and Turkey. Bangladesh and Bolivia are scheduled for 1993. In 1994 surveys will be administered in Burundi, Central African Republic, Cote d'Ivoire, Guatemala, Haiti, Indonesia, Kazakhstan, Mali, Nigeria, Tanzania, Uganda, and Zimbabwe. PMID:12287320

  3. The crystal structure of methane phase III

    NASA Astrophysics Data System (ADS)

    Neumann, Marcus A.; Press, Werner; Nöldeke, Christian; Asmussen, Bernd; Prager, Michael; Ibberson, Richard M.

    2003-07-01

    Methane is the simplest organic molecule, and like many supposedly simple molecular materials it has a rich phase diagram. While crystal structures could be determined for two of the solid phases, that of the low temperature phase III remained unsolved. Using high-resolution neutron powder diffraction and a direct-space Monte Carlo simulated annealing approach, this fundamental structure has now finally been solved. It is orthorhombic with space group Cmca, and 16 molecules in the unit cell. The structure is closely related to that of phase II, yet is no subgroup of it.

  4. 75 FR 14575 - Voting Equipment Evaluations Phase III

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-26

    ... National Institute of Standards and Technology Voting Equipment Evaluations Phase III AGENCY: National... Phase III of the benchmark research for voting equipment used in an election in 2008 or later and/ or... Institute of Standards and Technology (NIST) will be conducting Phase III research on voting equipment...

  5. Advanced Emissions Control Development Program: Phase III

    SciTech Connect

    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 high

  6. Space Phase III - The commercial era dawns

    NASA Technical Reports Server (NTRS)

    Allnutt, R. F.

    1983-01-01

    After the 'Phase I' of space activities, the period bounded by Sputnik and Apollo, 'Phase II', has been entered, a phase in which concerns over the use and the protection of space assets which support national security predominate. However, it is only when the commercial motive becomes prominent that human activity in new regions truly prospers and enters periods of exponential growth. It is believed that there are increasing signs that such a period, called 'Space Phase III', may be coming soon. A description is presented of developments and results upon which this conclusion is based. Since 1980, there have been three developments of great importance for the future of space activities. Six highly successful flights have demonstrated that the Space Shuttle concept works. A series of Soviet missions are related to the emergence of a capability to construct and service modular space stations. Successful tests of the European Ariane 1 indicate an end to U.S. monopoly with respect to the provision of launch services to the Western World.

  7. Benchmark On Sensitivity Calculation (Phase III)

    SciTech Connect

    Ivanova, Tatiana; Laville, Cedric; Dyrda, James; Mennerdahl, Dennis; Golovko, Yury; Raskach, Kirill; Tsiboulia, Anatoly; Lee, Gil Soo; Woo, Sweng-Woong; Bidaud, Adrien; Patel, Amrit; Bledsoe, Keith C; Rearden, Bradley T; Gulliford, J.

    2012-01-01

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

  8. CONVERSION EXTRACTION DESULFURIZATION (CED) PHASE III

    SciTech Connect

    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 with

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

    PubMed

    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.

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

    SciTech Connect

    Winters, W.I.

    1996-01-01

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

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Sequential designs for phase III clinical trials incorporating treatment selection.

    PubMed

    Stallard, Nigel; Todd, Susan

    2003-03-15

    Most statistical methodology for phase III clinical trials focuses on the comparison of a single experimental treatment with a control. An increasing desire to reduce the time before regulatory approval of a new drug is sought has led to development of two-stage or sequential designs for trials that combine the definitive analysis associated with phase III with the treatment selection element of a phase II study. In this paper we consider a trial in which the most promising of a number of experimental treatments is selected at the first interim analysis. This considerably reduces the computational load associated with the construction of stopping boundaries compared to the approach proposed by Follman, Proschan and Geller (Biometrics 1994; 50: 325-336). The computational requirement does not exceed that for the sequential comparison of a single experimental treatment with a control. Existing methods are extended in two ways. First, the use of the efficient score as a test statistic makes the analysis of binary, normal or failure-time data, as well as adjustment for covariates or stratification straightforward. Second, the question of trial power is also considered, enabling the determination of sample size required to give specified power.

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

    SciTech Connect

    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.

  16. High pressure phase transition in group III nitrides compounds

    NASA Astrophysics Data System (ADS)

    Soni, Shubhangi; Verma, S.; Kaurav, Netram; Choudhary, K. K.

    2016-05-01

    Using an effective interionic interaction potential (EIOP), the pressure induced structural phase transformation from ZnS-type (B3) to NaCl-type (B1) structure in group III Post-Transition Metal Nitrides [TMN; TM=Ga and Tl] were investigated. The long range Coulomb, van der Waals (vdW) interaction and the short-range repulsive interaction upto second-neighbor ions within the Hafemeister and Flygare approach with modified ionic charge are properly incorporated in the EIOP. The vdW coefficients are computed following the Slater-Kirkwood variational method, as both the ions are polarizable. The estimated value of the phase transition pressure (Pt) and the magnitude of the discontinuity in volume at the transition pressure are consistent as compared to the reported data.

  17. Reactor physics studies in the GCFR Phase III critical assembly

    SciTech Connect

    Morman, J A

    1980-03-01

    The third phase of the gas cooled fast reactor (GCFR) program, ZPR-9 Assembly 30, is based on a multi-zoned core of PuO/sub 2/-UO/sub 2/ with radial and axial blankets of UO/sub 2/. Studies performed in this assembly will be compared to the previous phases of the GCFR program and will help to define parameters in this power-flattened demonstration plant-type core. Measurements in the Phase III program included small sample reactivity worths of various materials, central reaction rates and reaction rate distributions, absorption-to-fission ratios and the central point conversion ratio and the worth of steam entry into a small central zone. The reactivity change associated with the construction of a central pin zone in the core and axial blanket was measured. Reaction rate and steam entry measurements were repeated in the pin environment. Standard analysis methods using ENDF/B-IV data are described and the results are compared to measurements performed during the program.

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

    NASA Technical Reports Server (NTRS)

    Madson, Michael D.

    2004-01-01

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

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

    SciTech Connect

    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.

  20. Glycerol and NEFA kinetics in long-term fasting king penguins: phase II versus phase III.

    PubMed

    Bernard, S F; Fayolle, C; Robin, J-P; Groscolas, R

    2002-09-01

    In spontaneously fasting birds such as penguins, below a body mass threshold corresponding to the phase II-phase III transition, a metabolic and hormonal shift occurs and feeding behaviour is stimulated ('refeeding signal'). The major aim of this study was to determine whether a decrease in non-esterified fatty acid (NEFA) release from adipose tissue could be a component of this signal. Lipolytic fluxes and primary triacylglycerol:fatty acid (TAG:FA) cycling were determined in vivo in breeding, fasting king penguins (Aptenodytes patagonicus) using continuous infusions of 2-[3H]glycerol and 1-[14C]palmitate under field conditions. In phase II (after approximately 8 days of fasting, large fat stores, body protein spared, N=8), the rate of appearance (R(a)) of glycerol and of NEFA were 5.7+/-0.8 and 10.5+/-0.4 micromol kg(-1) min(-1), respectively, and the percentage of primary TAG:FA cycling was 41+/-7%. In phase III (after approximately 25 days of fasting, fat stores reduced by fourfold, increased body protein catabolism, N=9), R(a) glycerol kg(-1) body mass remained unchanged, whereas R(a) glycerol kg(-1) fat mass and R(a) NEFA kg(-1) body mass were increased by 2.8-fold and 1.5-fold, respectively. Increased R(a) glycerol kg(-1) fat mass was possibly the result of a 3.5-fold increase in circulating glucagon, the increased R(a) NEFA kg(-1) body mass being attributable to decreased primary TAG:FA cycling. Thus, triggering of the refeeding signal that redirects the behavior of fasting, incubating penguins from incubation towards the search for food after entrance into phase III cannot be ascribed to a reduction in lipolytic fluxes and NEFA availability. PMID:12151380

  1. GLASS COMPOSITIONS FOR THE NEPHELINE PHASE III STUDY

    SciTech Connect

    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.

  2. EXPERIMENTAL RESULTS OF THE NEPHELINE PHASE III STUDY

    SciTech Connect

    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

  3. Dynamic observation of phase transformation behaviors in indium(III) selenide nanowire based phase change memory.

    PubMed

    Huang, Yu-Ting; Huang, Chun-Wei; Chen, Jui-Yuan; Ting, Yi-Hsin; Lu, Kuo-Chang; Chueh, Yu-Lun; Wu, Wen-Wei

    2014-09-23

    Phase change random access memory (PCRAM) has been extensively investigated for its potential applications in next-generation nonvolatile memory. In this study, indium(III) selenide (In2Se3) was selected due to its high resistivity ratio and lower programming current. Au/In2Se3-nanowire/Au phase change memory devices were fabricated and measured systematically in an in situ transmission electron microscope to perform a RESET/SET process under pulsed and dc voltage swept mode, respectively. During the switching, we observed the dynamic evolution of the phase transformation process. The switching behavior resulted from crystalline/amorphous change and revealed that a long pulse width would induce the amorphous or polycrystalline state by different pulse amplitudes, supporting the improvement of the writing speed, retention, and endurance of PCRAM. PMID:25133955

  4. CIM5 Phase III base process development results

    SciTech Connect

    Witt, D.C.

    2000-01-06

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

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

    SciTech Connect

    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.

  6. Quantitative phase-amplitude microscopy. III. The effects of noise.

    PubMed

    Paganin, D; Barty, A; McMahon, P J; Nugent, K A

    2004-04-01

    We explore the effect of noise on images obtained using quantitative phase-amplitude microscopy - a new microscopy technique based on the determination of phase from the intensity evolution of propagating radiation. We compare the predictions with experimental results and also propose an approach that allows good-quality quantitative phase retrieval to be obtained even for very noisy data.

  7. A New Approach to Designing Phase I-II Cancer Trials for Cytotoxic Chemotherapies

    PubMed Central

    Bartroff, Jay; Lai, Tze Leung; Narasimhan, Balasubramanian

    2014-01-01

    Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II hypothesis test of H0: p ≤ p0, where p is the probability of efficacy at the estimated maximum tolerated dose (MTD) η̂ from Phase I and p0 is the baseline efficacy rate. Standard practice for Phase II remains to treat p as a fixed, unknown parameter and to use Simon’s 2-stage design with all patients dosed at η̂. We propose a Phase I-II design that addresses the uncertainty in the estimate p = p(η̂) in H0 by using sequential generalized likelihood theory. Combining this with a Phase I design that incorporates efficacy data, the Phase I-II design provides a common framework that can be used all the way from the first dose of Phase I through the final accept/reject decision about H0 at the end of Phase II, utilizing both toxicity and efficacy data throughout. Efficient group sequential testing is used in Phase II that allows for early stopping to show treatment effect or futility. The proposed Phase I-II design thus removes the artificial barrier between Phase I and Phase II, and fulfills the objectives of searching for the MTD and testing if the treatment has an acceptable response rate to enter into a Phase III trial. PMID:24577750

  8. National Geoscience Data Repository System -- Phase III: Implementation and Operation of the Repository

    SciTech Connect

    Keane, Christopher M.

    2002-05-28

    The National Geoscience Data Repository System, Phase III was an operational project focused on coordinating and facilitating transfers of at-risk geoscience data from the private sector to the public domain.

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

    PubMed Central

    Antoniou, Miranta; Jorgensen, Andrea L; Kolamunnage-Dona, Ruwanthi

    2016-01-01

    Background 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. Methods and Findings 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. Conclusions Our in-depth overview provides future researchers with clarity in definition, methodology and terminology for biomarker-guided adaptive trial designs. PMID:26910238

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

    SciTech Connect

    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.

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

    ERIC Educational Resources Information Center

    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…

  12. Phase III of the USO Solar Vector Magnetograph

    NASA Astrophysics Data System (ADS)

    Gosain, S.; Venkatakrishnan, P.

    The solar vector magnetograph (SVM) is a modern imaging spectropolarimeter installed at Udaipur Solar Observatory (USO). Earlier phases saw the development of the instrument using off-the-shelf components with in-house software development. Subsequently, improvements were done in the opto-mechanical design of the sub-systems and the telescope tracking system. The third phase of the instrument development saw three major improvements: (1) installation of a web-camera-based telescope guiding system, developed in-house, (2) high-cadence spectropolarimetry using liquid-crystal variable retarders and a fast CCD camera, and (3) inclusion of the Na I D1 line for chromospheric observations, in addition to the regularly used photospheric Fe I 6302 Å line.

  13. Chromium(III) oxidation by three poorly crystalline manganese(IV) oxides. 2. Solid phase analyses.

    PubMed

    Landrot, Gautier; Ginder-Vogel, Matthew; Livi, Kenneth; Fitts, Jeffrey P; Sparks, Donald L

    2012-11-01

    Layered, poorly crystalline Mn(IV)O(2) phases are abundant in the environment. These mineral phases may rapidly oxidize Cr(III) to more mobile and toxic Cr(VI) in soils. There is still, however, little knowledge of how Cr(III) oxidation by Mn(IV)O(2) proceeds at the microscopic and molecular levels. Therefore, the sorption mechanisms of Cr(III) and Cr(VI) on Random Stacked Birnessite (RSB), δ-MnO(2), and Acid Birnessite (AB) were determined by Extended X-ray Absorption Fine Structure Spectroscopy (EXAFS). These three synthetic Mn(IV)O(2), which are poorly crystalline phases and have layered structures, were reacted with 50 mM Cr(III) at pH 2.5, 3, and 3.5 before being analyzed by EXAFS. The results indicated that Cr(VI) was loosely sorbed as an outer-sphere complex on Mn(IV)O(2), while Cr(III) was tightly sorbed as an inner-sphere complex. Further research is needed to understand why Cr(III) stopped being significantly oxidized by Mn(IV)O(2) after 30 min. This study, however, demonstrated that the formation of a Cr surface precipitate is not necessarily responsible for the cessation in Cr(III) oxidation. Indeed, no Cr surface precipitate was detected at the microscopic and molecular levels on Mn(IV)O(2) surfaces reacted with Cr(III) for 1 h, although the Cr(III) oxidation ceased before 1 h of reaction at most employed experimental conditions. PMID:23050862

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

    ERIC Educational Resources Information Center

    Thurber, John C.

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

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

    SciTech Connect

    Noel, Donna

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

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

    1993-12-31

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

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

    SciTech Connect

    Ruff, D.T.

    1994-10-17

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

  19. Tegress™ Urethral Implant Phase III Clinical Experience and Product Uniqueness

    PubMed Central

    Dmochowski, Roger R

    2005-01-01

    Advances in materials technology, coupled with a heightened understanding of wound healing and tissue-materials interactions in the lower urinary tract, have led to the development of a variety of new urethral bulking agents that are expected to be available in the near future. Experience with such bulking agents continues to grow and study results are disseminated as more clinical trials are initiated and completed. The intention of this report is to review the characteristics and initial clinical results for one of these new agents: Tegress™ Urethral Implant (C. R. Bard, Inc., Murray Hill, NJ). This material, with unique phase-change properties upon exposure to body temperature fluids, offers ease of injection and requires less volume for clinical effect than bovine collagen. Additionally, Tegress Urethral Implant performance in clinical trials has suggested improved durability and correspondingly higher continence and improvement rates versus bovine collagen. As these materials evolve, an understanding of preferential implant techniques is being gained also. Delivery method and implant site may prove to substantially alter the biologic activity of these compounds. As outlined in this review, experience with Tegress Implant resulted in changes in delivery technique that translated into improved materials and tissue interaction. PMID:16985873

  20. Situational Lightning Climatologies for Central Florida: Phase III

    NASA Technical Reports Server (NTRS)

    Barrett, Joe H., III

    2008-01-01

    This report describes work done by the Applied Meteorology Unit (AMU) to add composite soundings to the Advanced Weather Interactive Processing System (AWIPS). This allows National Weather Service (NWS) forecasters to compare the current atmospheric state with climatology. In a previous phase, the AMU created composite soundings for four rawinsonde observation stations in Florida, for each of eight flow regimes. The composite soundings were delivered to the NWS Melbourne (MLB) office for display using the NSHARP software program. NWS MLB requested that the AMU make the composite soundings available for display in AWIPS. The AMU first created a procedure to customize AWIPS so composite soundings could be displayed. A unique four-character identifier was created for each of the 32 composite soundings. The AMU wrote a Tool Command Language/Tool Kit (TcVTk) software program to convert the composite soundings from NSHARP to Network Common Data Form (NetCDF) format. The NetCDF files were then displayable by AWIPS.

  1. Age Strengthening of Gray Cast Iron Phase III

    SciTech Connect

    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.

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

    SciTech Connect

    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.

  3. Negative results in phase III trials of complex interventions: cause for concern or just good science?

    PubMed

    Crawford, Mike J; Barnicot, Kirsten; Patterson, Sue; Gold, Christian

    2016-07-01

    Not all interventions that show promise in exploratory trials will be supported in phase III studies. But the high failure rate in recent trials of complex mental health interventions is a concern. Proper consideration of trial processes and greater use of adaptive trial designs could ensure better use of available resources. PMID:27369475

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

    ERIC Educational Resources Information Center

    Love, Jessica June

    2013-01-01

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

  5. What Works in Oklahoma Schools: A Comprehensive Needs Assessment of Oklahoma Schools. Phase III Action Steps

    ERIC Educational Resources Information Center

    Marzano Research Laboratory, 2011

    2011-01-01

    This document contains the Phase III report from the "What Works in Oklahoma Schools" study. As opposed to describing the findings from the study that was conducted, it provides a tool-kit that can be used by Oklahoma principals and teachers to determine the best courses of action for their schools and classrooms. The tools provided in this report…

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

    SciTech Connect

    O'Neil, Lori Ross; Conway, T. J.; Tobey, D. H.; Greitzer, Frank L.; Dalton, Angela C.; Pusey, Portia K.

    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.

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

    SciTech Connect

    O'Neil, Lori Ross; Conway, T. J.; Tobey, D. H.; Greitzer, Frank L.; Dalton, Angela C.; Pusey, Portia K.

    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.

  8. Project NECESSITIES, Phase III. Volume IV: Teaching Materials for Kindergarten and First Grade.

    ERIC Educational Resources Information Center

    Abt Associates, Inc., Cambridge, MA.

    Phase III, Volume IV, Part A of Project NECESSITIES consists of 10 activities intended for kindergarten-aged American Indian (including Eskimo) children. Some of the supplementary materials needed to teach these activities ("Symbol Formation" and "An Animal Alphabet") are appended. The unit, entitled Learning to Communicate, begins with non-verbal…

  9. Thermodynamic analysis of III-V semiconductor alloys grown by metalorganic vapor phase epitaxy

    NASA Astrophysics Data System (ADS)

    Asai, Toshihiro; Dandy, David S.

    2000-10-01

    A thermodynamic analysis has been applied to systematically study III-V semiconductor alloy deposition, including nitrides grown by metalorganic vapor phase epitaxy. The predicted solid compositions of a number of ternary and quaternary alloys, including AlxGa1-xPyAs1-y, are compared with experimental data. For phosphorus-containing alloys, introduction of a parameter f representing incomplete PH3 pyrolysis yields good agreement with experimental data. It is shown that the input mole fraction of the group III metalorganic sources influences the incorporation of P into the solid for these alloys. Solid composition is also calculated for nitride alloys as a function of inlet gas concentration. To date, thermodynamic models have been applied solely to predict N solubility limits for nitride alloys where mixing occurs on the group V sublattice. The present model is used to predict N solid compositions in ternary and quaternary alloys, and it is demonstrated that these values are below the theoretical solubility limits for In-containing nitrides. The role of H2 in the carrier gas is investigated for III-N-V, III-III-N-V, and III-N-V-V systems.

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

    PubMed Central

    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 Discrepancy Index (DI) category, and fulfills part of the requirements for obtaining BBO Diploma. PMID:25279531

  11. Predicted band structures of III-V semiconductors in the wurtzite phase

    SciTech Connect

    De, A.; Pryor, Craig E.

    2010-04-15

    While non-nitride III-V semiconductors typically have a zinc-blende structure, they may also form wurtzite crystals under pressure or when grown as nanowhiskers. This makes electronic structure calculation difficult since the band structures of wurtzite III-V semiconductors are poorly characterized. We have calculated the electronic band structure for nine III-V semiconductors in the wurtzite phase using transferable empirical pseudopotentials including spin-orbit coupling. We find that all the materials have direct gaps. Our results differ significantly from earlier ab initio calculations, and where experimental results are available (InP, InAs, and GaAs) our calculated band gaps are in good agreement. We tabulate energies, effective masses, and linear and cubic Dresselhaus zero-field spin-splitting coefficients for the zone-center states. The large zero-field spin-splitting coefficients we find may facilitate the development of spin-based devices.

  12. Solid-phase synthesis of protected peptides using new cobalt(III) ammine linkers.

    PubMed

    Arbo, B E; Isied, S S

    1993-08-01

    Cobalt(III) ammine complexes of the type cis-[CoL4(4-AMB)O-AA-Boc](CF3SO3)2, where L4 = bisethylenediamine (en)2 or tetraammine (NH3)4, and 4-AMB = 4-(aminomethyl)benzoic acid, have been synthesized and used as linkers to polystyrene resins for solid-phase synthesis of protected peptides. Boc/t-Bu-protected [Leu5]enkephalin was assembled on the two different Co(III) resins, and then cleaved from the resins by reduction of the Co(III) center in 93-96% yield. HPLC-purified protected [Leu5]enkephalin was obtained in 67-69% overall yield and characterized by amino acid analysis and 1H NMR. Stepwise synthesis on the Co(en)2-resin was also used in the assembly of Boc-Asp(OcHex)-Arg(Mts)-Gly-Asp(OcHex)-Ala-Pro-Lys(2Cl-Z)-Gl y-OH, a sequence from collagen alpha 1 Type 1. The protected peptide was cleaved from the Co(III) resin in 74% yield, and the HPLC-purified nonapeptide was characterized by amino acid analysis, 1H NMR and liquid secondary-ion mass spectrometry (LSIMS). New routes are described for the synthesis of isomerically pure Co(III) anchor complexes. The Co(III) resins were found to be compatible with both the tert-butyloxycarbonyl (Boc) and the 9-fluorenylmethoxycarbonyl (Fmoc) N alpha-protecting group strategies used in solid-phase peptide synthesis.

  13. Phase variable type III restriction-modification systems of host-adapted bacterial pathogens.

    PubMed

    Fox, Kate L; Srikhanta, Yogitha N; Jennings, Michael P

    2007-09-01

    Phase variation, the high-frequency on/off switching of gene expression, is a common feature of host-adapted bacterial pathogens. Restriction-modification (R-M) systems, which are ubiquitous among bacteria, are classically assigned the role of cellular defence against invasion of foreign DNA. These enzymes are not obvious candidates for phase variable expression, a characteristic usually associated with surface-expressed molecules subject to host immune selection. Despite this, numerous type III R-M systems in bacterial pathogens contain repetitive DNA motifs that suggest the potential for phase variation. Several roles have been proposed for phase variable R-M systems based on DNA restriction function. However, there is now evidence in several important human pathogens, including Haemophilus influenzae, Neisseria meningitidis and Neisseria gonorrhoeae, that these systems are 'phasevarions' (phase variable regulons) controlling expression of multiple genes via a novel epigenetic mechanism. PMID:17714447

  14. Effect of licorice on the induction of phase II metabolizing enzymes and phase III transporters and its possible mechanism.

    PubMed

    Gong, Hui; Li, Huan-De; Yan, Miao; Zhang, Bi-Kui; Jiang, Pei; Fan, Xin-Rong; Deng, Yang

    2014-12-01

    Licorice has a marked detoxifying effect that can treat drug poisoning and/or relieve adverse effects. However, the exact mechanism of this action is not entirely elucidated, but is believed to be related to the modulation of drug disposition when interacting with other drugs. Additionally, Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in mediating phase II xenobiotic metabolizing enzymes (XMEs) and phase III transporters. In the present study, we showed that licorice induced the mRNA expression of phase II XMEs UDP-glucuronosyltransferases 1A1 (UGT1A1), glutamate cysteine ligase (GCL), glutathione-s-transferase (GST) and phase III transporters multidrug resistance protein 2 (MRP2), as well as a rapid increase in Nrf2 nuclear accumulation. These findings suggests that licorice may intervene in the Nrf2 signal pathway to induce UGT1A1, GCLC, GST and MRP2, which provide a novel mechanism for the use of licorice to treat drug poisoning and/or relieve adverse effects. PMID:25951662

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

    PubMed

    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. PMID:26785741

  16. Trimebutine-induced phase III-like activity in infants with intestinal motility disorders.

    PubMed

    Boige, N; Cargill, G; Mashako, L; Cezard, J P; Navarro, J

    1987-01-01

    Duodenal manometric recordings were performed in five male children (mean age 11.7 +/- 6.8 months) suffering from severe digestive pathology with clinical findings of dysmotility; they required total parenteral nutrition: one case of enteropathy following intestinal resection for congenital small bowel atresia, and four cases of intestinal pseudoobstruction. The basal 3-h fasting recordings showed complete disorganization of interdigestive activity characterized by an absence of migrating motor complexes and a marked basal hypomotility with motor indices lower than in control subjects. Intravenous trimebutine (3 mg/kg) produced a phase III-like activity 88 +/- 121 s after administration in four cases. The activity lasted 236 +/- 105 s and had a mean frequency of 11.75 +/- 0.86 waves/min. It was propagated aborally in the two patients having two duodenal recording sites. Trimebutine-induced phase III activity was followed by signs of peristalsis in two patients. PMID:3430262

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

    SciTech Connect

    1988-09-01

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

  18. On-line solid-phase extraction and multisyringe flow injection analysis of Al(III) and Fe(III) in drinking water.

    PubMed

    Vanloot, Pierre; Branger, Catherine; Margaillan, André; Brach-Papa, Christophe; Boudenne, Jean-Luc; Coulomb, Bruno

    2007-11-01

    A new analytical method was developed for on-line monitoring of residual coagulants (aluminium and iron salts) in potable water. The determination was based on a sequential procedure coupling an extraction/enrichment step of the analytes onto a modified resin and a spectrophotometric measurement of a surfactant-sensitized binary complex formed between eluted analytes and Chrome Azurol S. The optimization of the solid phase extraction was performed using factorial design and a Doehlert matrix considering six variables: sample percolation rate, sample metal concentration, flow-through sample volume (all three directly linked to the extraction step), elution flow rate, concentration and volume of eluent (all three directly linked to the elution step). A specific reagent was elaborated for sensitive and specific spectrophotometric determination of Al(III) and Fe(III), by optimizing surfactant and ligand concentrations and buffer composition. The whole procedure was automated by a multisyringe flow injection analysis (MSFIA) system. Detection limits of 4.9 and 5.6 microg L(-1) were obtained for Al(III) and Fe(III) determination , respectively, and the linear calibration graph up to 300 microg L(-1) (both for Al(III) and Fe(III)) was well adapted to the monitoring of drinking water quality. The system was successfully applied to the on-site determination of Al(III) and Fe(III) at the outlet of two water treatment units during two periods of the year (winter and summer conditions).

  19. Idaho Water Rental Pilot Project Probability/Coordination Study Resident Fish and Wildlife Impacts Phase III, 1997 Annual Report.

    SciTech Connect

    Leitzinger, Eric J.

    1998-10-01

    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.

  20. Phase III Technology for All Americans Project: Creating Assessment, Professional Development, and Program Standards for Technological Literacy.

    ERIC Educational Resources Information Center

    Dugger, William E., Jr.

    2001-01-01

    The goals of Phase III of the Technology for All Americans Project are to develop student assessment standards, professional development standards, program standards, and effective leaders. The project is based on the Standards for Technology Literacy, a NASA initiative. (JOW)

  1. Embracing failure: What the Phase III progesterone studies can teach about TBI clinical trials

    PubMed Central

    Stein, Donald G.

    2015-01-01

    Abstract Background: Despite positive preclinical studies and two positive Phase II clinical trials, two large Phase III clinical trials of progesterone treatment of acute traumatic brain injury (TBI) recently ended with negative results, so a 100% failure rate continues to plague the field of TBI trials. Methods: This paper reviews and analyses the trial structures and outcomes and discusses the implications of these failures for future drug and clinical trial development. Persistently negative trial outcomes have led to disinvestment in new drug research by companies and policy-makers and disappointment for patients and their families, failures which represent a major public health concern. The problem is not limited to TBI. Failure rates are high for trials in stroke, sepsis, cardiology, cancer and orthopaedics, among others. Results: This paper discusses some of the reasons why the Phase III trials have failed. These reasons may include faulty extrapolation from pre-clinical data in designing clinical trials and the use of subjective outcome measures that accurately reflect neither the nature of the deficits nor long-term quantitative recovery. Conclusions: Better definitions of injury and healing and better outcome measures are essential to change the embrace of failure that has dominated the field for over 30 years. This review offers suggestions to improve the situation. PMID:26274493

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

    PubMed Central

    Wang, Bushi; Ting, Naitee

    2014-01-01

    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. PMID:24432299

  3. Equilibrium Phase Diagrams for Stranski-Krastanov Structure Mode of III V Ternary Quantum Dots

    NASA Astrophysics Data System (ADS)

    Nakajima, Kazuo

    1999-04-01

    The strain, surface and interfacial energies of III V ternary systems were calculated for three kinds of structure modes: the Frank-van der Merwe (FM) mode, the Stranski-Krastanov (SK) mode and the Volmer-Weber (VW) mode. The free energy for each mode was estimated as functions of the thickness and composition or lattice misfit. Through comparison of the free energy of each mode, it was found that the thickness-composition phase diagrams of III V ternary systems can be determined only by considering the balance of the free energy and three kinds of structure modes appear in the phase diagrams. The SK mode appears only when the lattice misfit is large and/or the lattice layer is thick. The VW mode appears when the lattice misfit is large and the lattice layer is thin and only in the InPSb/InP and GaPSb/GaP systems which have the largest lattice misfit of III V ternary systems. The stable region of the SK mode in the GaPSb/GaP and InPSb/InP phase diagrams is largest of all because the composition dependence of the strain energy of these systems is stronger than that of the other systems. The critical number of lattice layers below which two-dimensional (2D) layers precede the three-dimensional (3D) nucleation in the SK mode at x=1.0 depends on the lattice misfit. In the InPSb/InP system, the smallest number of 2D layers precede the 3D nucleation in the SK mode.

  4. A Phase I-II Study of Postoperative Capecitabine-Based Chemoradiotherapy in Gastric Cancer

    SciTech Connect

    Jansen, Edwin; Crosby, Tom D.L.; Dubbelman, Ria; Bartelink, Harry; Verheij, Marcel

    2007-12-01

    Background: The Intergroup 0116 randomized study showed that postoperative 5-fluorouracil-based chemoradiotherapy improved locoregional control and overall survival in patients with gastric cancer. We hypothesized that these results could be improved further by using a more effective, intensified, and convenient chemotherapy schedule. Therefore, this Phase I-II dose-escalation study was performed to determine the maximal tolerated dose and toxicity profile of postoperative radiotherapy combined with concurrent capecitabine. Patients and Methods: After recovery from surgery for adenocarcinoma of the gastroesophageal junction or stomach, all patients were treated with capecitabine monotherapy, 1,000 mg/m{sup 2} twice daily for 2 weeks. After a 1-week treatment-free interval, patients received capecitabine (650-1,000 mg/m{sup 2} orally twice daily 5 days/week) in a dose-escalation schedule combined with radiotherapy on weekdays for 5 weeks. Radiotherapy was delivered to a total dose of 45 Gy in 25 fractions to the gastric bed, anastomoses, and regional lymph nodes. Results: Sixty-six patients were treated accordingly. Two patients went off study before or shortly after the start of chemoradiotherapy because of progressive disease. Therefore, 64 patients completed treatment as planned. During the chemoradiotherapy phase, 4 patients developed four items of Grade III dose-limiting toxicity (3 patients in Dose Level II and 1 patient in Dose Level IV). The predefined highest dose of capecitabine, 1,000 mg/m{sup 2} twice daily orally, was tolerated well and, therefore, considered safe for further clinical evaluation. Conclusions: This Phase I-II study shows that intensified chemoradiotherapy with daily capecitabine is feasible in postoperative patients with gastroesophageal junction and gastric cancer.

  5. Power and Sample Size for Randomized Phase III Survival Trials under the Weibull Model

    PubMed Central

    Wu, Jianrong

    2015-01-01

    Two parametric tests are proposed for designing randomized two-arm phase III survival trials under the Weibull model. The properties of the two parametric tests are compared with the non-parametric log-rank test through simulation studies. Power and sample size formulas of the two parametric tests are derived. The impact on sample size under mis-specification of the Weibull shape parameter is also investigated. The study can be designed by planning the study duration and handling nonuniform entry and loss to follow-up under the Weibull model using either the proposed parametric tests or the well known non-parametric log-rank test. PMID:24895942

  6. Forming your phase III trial's data and safety monitoring board: a perspective on safety.

    PubMed

    Wittes, Janet

    2004-11-01

    A data safety monitoring board (DSMB) established in a phase III trial to monitor the safety of participants in a clinical trial views itself as protecting participants and ensuring the integrity of the study. The DSMB should operate under a clear charter, with expectations understood by all members of the Board, the sponsor, and the investigators. Sponsors must trust their DSMBs. The sponsor must give the DSMB the tools and the data that it needs to operate effectively in protecting the safety of the participants.

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

    SciTech Connect

    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 results

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

    SciTech Connect

    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

  9. Evaluation of a method for arsenic(III) and antimony(III) determination by vapour phase molecular absorption spectrometry using graphite furnace volati

    NASA Astrophysics Data System (ADS)

    Galban, J.; Marcos, E.; Lamana, J.; Castillo, J. R.

    1993-01-01

    This paper presents a procedure for determining As(III) and Sb(III) by vapour phase molecular absorption spectrometry (VPMAS). The chlorides of these elements are volatilized from aqueous solutions in a L'vov platform inside the graphite furnace of an atomic absorption spectrophotometer. Molecular absorption is measured at 205 nm for arsenic chloride and 220 nm for antimony chloride. Both species are formed in the sample drying stage. A study of the temperature program led to different results in each case. In the case of arsenic, a two-step program (one mixed drying and volatilization step, and another cleaning step) is found to be best, whereas in the case of antimony, three separate steps can be used (drying, volatilization and cleaning). In both cases, optimum volatilization was obtained with low HCl concentrations, and volatilization fell off sharply as HCl concentration increased. Under optimum generation and determination conditions, the linear response range is from 0.06 to 3.75 μg for As(III), and from 0.30 to 5.0 μg for Sb(III) with relative standard deviations of 2.1% for As(III) and 2.5% for Sb(III). The effect of other anions and cations on the arsenic analytical signal was studied, and other halides were found to interfere. The method was applied to arsenic determination in an arsenic ore.

  10. Defect Analysis in III-V Semiconductor Thin Films Grown by Hydride Vapor Phase Epitaxy

    NASA Astrophysics Data System (ADS)

    Schulte, Kevin Louis

    Hydride vapor phase epitaxy (HVPE) is an epitaxial growth technique renowned for its ability to grow III-V semiconductors at high growth rates using lower cost reagents compared to metal-organic vapor phase epitaxy (MOVPE), the current industry standard. Recent interest in III-V photovoltaics has led to increased attention on HVPE. While the technique came to maturity in the 70s, much is unknown about how defects incorporate in HVPE-grown materials. Further understanding of how defects incorporate in III-V materials grown by HVPE is necessary to facilitate wider adoption of the technique. This information would inform strategies for minimizing and eliminating defects in HVPE materials, allowing for the formation of high performance devices. This investigation presents a study of multiple defects in III-V semiconductors grown by HVPE in the context of specific device applications, spanning point defects comprised of individual atoms to extended defects which propagate throughout the crystal. The incorporation of the arsenic anti-site defect, AsGa, intrinsic point defect was studied in high growth rate GaAs layers with potential photovoltaic applications. Relationships between growth conditions and incorporation of AsGa in GaAs epilayers were determined. The incorporation of AsGa depended strongly on the growth conditions employed, and a model was developed to predict the concentration of anti-site defects as a function of those growth conditions. Dislocations and anti-phase domain boundaries (APDBs), two types of extended defects, were investigated in the heteroepitaxial GaAs/Ge system. It was found that the use of 6° miscut substrates and specific growth temperatures led to elimination of APDBs. Dislocation densities were reduced through the use of high growth temperatures. The third and final application investigated was the growth of InxGa1-xAs metamorphic buffer layers (MBLs) by HVPE. The relationships between the growth conditions and the alloy composition

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

    PubMed

    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.

  12. Costa Rica.

    PubMed

    1986-05-01

    This discussion of Costa Rica focuses on: geography, people and history, government, political conditions, the economy, defense, foreign relations, and relations between the US and Costa Rica. In 1985 the population totaled 2.6 million with an annual growth rate of 2.6%. The infant mortality rate is 15.2/1000; life expectancy is 67.5 years for men and 71.9 years for women. Costa Rica, the 2nd smallest Central American country, is located in a narrow strip between Panama and Nicaragua. Costa Ricans are overwhelmingly of European descent. Although preominantly Spanish, there also are many Costa Ricans of German, Dutch, and Swiss origin. The indigenous Indian population numbers about 20,000, 20% fewer than inhabited Costa Rica when the Spanish first settled in 1522. Blacks, descendants of 19th century Jamaican immigrant workers, constitute a significant English-speaking minority of 30,000. Costa Rica is a democratic republic with a strong systems of checks and balances. The president and 57 legislative assembly deputies are elected for 4-year terms. Costa Rica's political system has contrasted with that of its neighbors. The nation has steadily developed and maintained democratic institutions and an orderly, constitutional process of government succession. Costa Rica faces severe challenges to its economic stability, although traditionally it is one of the strongest nations in the region. Increases in government spending in the late 1970s and higher world prices for coffee and other important Costa Rican exports stimulated the economy, creating inflationary pressure. The government is pursuing a course of disciplined management. The country is an outsponken and active member of the international community. The cordial relationship between Costa Rica and the US is based on mutual respect for democratic traditions, common goals, and a relationship free from serious political disagreement. PMID:12178136

  13. Effect of Carbon Ion Radiotherapy for Sacral Chordoma: Results of Phase I-II and Phase II Clinical Trials

    SciTech Connect

    Imai, Reiko; Kamada, Tadashi; Tsuji, Hiroshi; Sugawara, Shinji; Serizawa, Itsuko; Tsujii, Hirohiko; Tatezaki, Shin-ichiro

    2010-08-01

    Purpose: To summarize the results of treatment for sacral chordoma in Phase I-II and Phase II carbon ion radiotherapy trials for bone and soft-tissue sarcomas. Patients and Methods: We performed a retrospective analysis of 38 patients with medically unresectable sacral chordomas treated with the Heavy Ion Medical Accelerator in Chiba, Japan between 1996 and 2003. Of the 38 patients, 30 had not received previous treatment and 8 had locally recurrent tumor after previous resection. The applied carbon ion dose was 52.8-73.6 Gray equivalents (median, 70.4) in a total of 16 fixed fractions within 4 weeks. Results: The median patient age was 66 years. The cranial tumor extension was S2 or greater in 31 patients. The median clinical target volume was 523 cm{sup 3}. The median follow-up period was 80 months. The 5-year overall survival rate was 86%, and the 5-year local control rate was 89%. After treatment, 27 of 30 patients with primary tumor remained ambulatory with or without supportive devices. Two patients experienced severe skin or soft-tissue complications requiring skin grafts. Conclusion: Carbon ion radiotherapy appears effective and safe in the treatment of patients with sacral chordoma and offers a promising alternative to surgery.

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Phase I--II study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine.

    PubMed

    Kimura, K; Yamada, K; Uzuka, Y; Maekawa, T; Takaku, F; Shimoyama, M; Ogawa, M; Amaki, I; Osamura, S; Ito, M; Sakai, Y; Oguro, M; Hattori, K; Hoshino, A; Hirota, Y; Ohta, K; Nakamura, T; Masaoka, T; Kimura, I; Ichimaru, M

    1981-01-01

    A phase I-II study of N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BH-AC) was conducted by a cooperative study group. In phase I study, a total of 126 patients, 64 of whom had metastatic solid tumors and 62 of whom had leukemia, were administered BH-AC in a single IV dose at day 1 only or in daily IV doses for 3 to 21 days, with dose ranges of 1.5--10.0 mg/kg. Side effects included nausea and vomiting, which were significantly less in incidence and severity than those observed with ara-C. Myelosuppressive toxicity became severe with doses 3.6--5.0 mg/kg per day x 10 days. In phase II study, a total of 37 adult patients with acute leukemia were entered in the study. Responses were noted, with an overall rate of 35% complete remission. Of th 26 patients with AML, there were 13 CR. The recommended schedule of treatment for BH-AC, based on our data, is daily infusion of 4--5 mg/kg over 3 h for approximately 3 weeks. The results with BH-AC in patients with acute leukemia are superior to those which have been reported for ara-C.

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

    PubMed

    Schimmer, Joshua; Breazzano, Steven

    2015-12-01

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

  17. Flexible design of two-stage adaptive procedures for phase III clinical trials.

    PubMed

    Koyama, Tatsuki

    2007-07-01

    The recent popularity of two-stage adaptive designs has fueled a number of proposals for their use in phase III clinical trials. Many of these designs assign certain restrictive functional forms to the design elements of stage 2, such as sample size, critical value and conditional power functions. We propose a more flexible method of design without imposing any particular functional forms on these design elements. Our methodology permits specification of a design based on either conditional or unconditional characteristics, and allows accommodation of sample size limit. Furthermore, we show how to compute the P value, confidence interval and a reasonable point estimate for any design that can be placed under the proposed framework. PMID:17307399

  18. Phase III LDR rule proposes new treatment standards CWA/SDWA systems affected

    SciTech Connect

    1995-05-01

    On March 2, 1995, EPA took one more step toward fulfilling statutory/judicial mandates regarding the RCRA land disposal restrictions (LDR) program. Among the most significant aspects of this so-called Phase III LDR rule is the proposal of treatment standards for characteristic wastes managed in systems regulated by the Clean Water Act (CWA) and in Class I injection wells regulated under the Safe Drinking Water Act (SDWA). These regulations would also apply to zero-discharge systems that treat waste-water in a manner equivalent to that used by CWA dischargers (i.e., CWA-equivalent systems). According to EPA, promulgation of the proposed requirements could affect a large number of facilities that may be forced to treat their wastes for underlying hazardous constituents prior to disposal. 1 fig., 4 tabs.

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

    SciTech Connect

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

    1996-08-01

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

  20. Structural and phase transformation of A{sup III}B{sup V}(100) semiconductor surface in interaction with selenium

    SciTech Connect

    Bezryadin, N. N.; Kotov, G. I. Kuzubov, S. V.

    2015-03-15

    Surfaces of GaAs(100), InAs(100), and GaP(100) substrates thermally treated in selenium vapor have been investigated by transmission electron microscopy and electron probe X-ray microanalysis. Some specific features and regularities of the formation of A{sub 3}{sup III}B{sub 4}{sup VI} (100)c(2 × 2) surface phases and thin layers of gallium or indium selenides A{sub 2}{sup III}B{sub 3}{sup VI} (100) on surfaces of different A{sup III}B{sup V}(100) semiconductors are discussed within the vacancy model of surface atomic structure.

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

    NASA Technical Reports Server (NTRS)

    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

  2. Randomized phase III trial of pegfilgrastim versus filgrastim after autologus peripheral blood stem cell transplantation.

    PubMed

    Gerds, Aaron; Fox-Geiman, Mary; Dawravoo, Kevin; Rodriguez, Tulio; Toor, Amir; Smith, Scott; Kiley, Karen; Fletcher-Gonzalez, Donna; Hicks, Chindo; Stiff, Patrick

    2010-05-01

    Nonrandomized trials suggest that pegfilgrastim, a pegylated granulocyte colony-stimulating factor, could be used in lieu of filgrastim after autologus peripheral blood stem cell transplantation. This phase III, randomized, double-blinded, placebo-controlled trial compared the efficacy, costs, and safety of single-dose pegfilgrastim (single 6 mg dose) versus daily filgrastim (5 microg/kg/day) for this indication. Seventy-eight patients, matched for age, sex, underlying disease, stage, and CD34/kg transplant dose were enrolled. Cytokines were started on day +1 posttransplant and continued to an absolute neutrophil count (ANC) of 5x10(9)/L for 3 days or 10x10(9)/L for 1 day. The median time to neutrophil engraftment (ANC >1.5x10(9)/L for 3 days or 5x10(9)/L for 1 day) was the same in both groups (12 days). No differences in platelet engraftment (11 versus 13 days), number of platelet transfusions (5 versus 4), percent with positive cultures for bacterial pathogens (23% versus 15%), days of fever (1 versus 2), deaths prior to engraftment (1 versus 1), or duration of hospital stay (19 versus 19 days) were seen between the pegfilgrastim and filgrastim groups, respectively. Using the average wholesale price for doses used in this trial, there was a per-patient savings of $961 for the pegfilgrastim group (P < .001). This phase III study failed to demonstrate a difference in time to neutrophil engraftment or any clinical sequelae between pegfilgrastim and filgrastim when given post-APBSCT, with pegfilgrastim achieving a cost savings over filgrastim. PMID:20045479

  3. Unexpected relationships and inbreeding in HapMap phase III populations.

    PubMed

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

    2012-01-01

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

  4. Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.

    PubMed

    Robertson, David S; Prevost, A Toby; Bowden, Jack

    2016-09-30

    Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:27103068

  5. Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.

    PubMed

    Robertson, David S; Prevost, A Toby; Bowden, Jack

    2016-09-30

    Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  6. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC)

    PubMed Central

    Oki, E.; Murata, A.; Yoshida, K.; Maeda, K.; Ikejiri, K.; Munemoto, Y.; Sasaki, K.; Matsuda, C.; Kotake, M.; Suenaga, T.; Matsuda, H.; Emi, Y.; Kakeji, Y.; Baba, H.; Hamada, C.; Saji, S.; Maehara, Y.

    2016-01-01

    Backgrounds Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur–uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. Patients and methods The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20–80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500–600 mg/day on days 1–5, followed by 2 days rest) or S-1 (80–120 mg/day on days 1–28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. Results In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63–0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. Conclusion One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection. PMID:27056996

  7. Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial

    PubMed Central

    Feng, Yan-Ru; Zhu, Yuan; Liu, Lu-Ying; Wang, Wei-Hu; Wang, Shu-Lian; Song, Yong-Wen; Wang, Xin; Tang, Yuan; Liu, Yue-Ping; Ren, Hua; Fang, Hui; Zhang, Shi-Ping; Liu, Xin-Fan; Yu, Zi-Hao; Li, Ye-Xiong; Jin, Jing

    2016-01-01

    The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3–4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis. PMID:27014909

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

    SciTech Connect

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

    SciTech Connect

    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.

  10. Erythropoietin Neuroprotection in Neonatal Cardiac Surgery: A Phase I/II Safety and Efficacy Trial

    PubMed Central

    Andropoulos, Dean B.; Brady, Ken; Easley, R. Blaine; Dickerson, Heather A.; Voigt, Robert G.; Shekerdemian, Lara S.; Meador, Marcie R.; Eisenman, Carol A.; Hunter, Jill V.; Turcich, Marie; Rivera, Carlos; McKenzie, E. Dean; Heinle, Jeffrey S.; Fraser, Charles D.

    2012-01-01

    Objectives Neonates undergoing complex congenital heart surgery have a significant incidence of neurological problems. Erythropoietin has anti-apoptotic, anti-excitatory, and anti-inflammatory properties to prevent neuronal cell death in animal models, and improves neurodevelopmental outcomes in full term neonates with hypoxic ischemic encephalopathy. We designed a prospective phase I/II trial of erythropoietin neuroprotection in neonatal cardiac surgery to assess safety, and indicate efficacy. Methods Neonates undergoing surgery for D-transposition of the great vessels, hypoplastic left heart syndrome, or aortic arch reconstruction were randomized to 3 perioperative doses of erythropoietin, or placebo. Neurodevelopmental testing with Bayley Scales of Infant and Toddler Development III was performed at age 12 months. Results 59 patients received study drug. Safety profile, including MRI brain injury, clinical events, and death, was not different between groups. 3 patients in each group died. 42 patients (22 erythropoietin, 20 placebo, 79% of survivors) returned for 12-month follow-up. The mean Cognitive Scores were erythropoietin, 101.1 ± 13.6, placebo, 106.3 ± 10.8 (p=0.19); Language Scores were erythropoietin 88.5 ± 12.8, placebo 92.4 ± 12.4 (p=0.33); and Motor Scores were erythropoietin 89.9 ± 12.3, placebo 92.6 ± 14.1, (p=0.51). Conclusions Safety profile for erythropoietin administration was not different than placebo. Neurodevelopmental outcomes were not different between groups, however this pilot study was not powered to definitively address this outcome. Lessons learned from the current study suggest optimized study design features for a larger prospective trial to definitively address the utility of erythropoietin for neuroprotection in this population. PMID:23102686

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

    PubMed Central

    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

  12. Promising short-term clinical results of the cementless Oxford phase III medial unicondylar knee prosthesis

    PubMed Central

    van Dorp, Karin B; Breugem, Stefan JM; Bruijn, Daniël J; Driessen, Marcel JM

    2016-01-01

    AIM: To investigate the short-term clinical results of the Oxford phase III cementless medial unicondylar knee prosthesis (UKP) compared to the cemented medial UKP. METHODS: We conducted a cross-sectional study in a tertairy orthopedic centre between the period of May 2010 and September 2012. We included 99 medial UKP in 97 patients and of these UKP, 53 were cemented and 46 were cementless. Clinical outcome was measured using a questionnaire, containing a visual analogue scale (VAS) for pain, Oxford Knee score, Kujala score and SF-12 score. Knee function was tested using the American Knee Society score. Complications, reoperations and revisions were recorded. Statistical significance was defined as a P value < 0.05. RESULTS: In a mean follow-up time of 19.5 mo, three cemented medial UKP were revised to a total knee prosthesis. Reasons for revision were malrotation of the tibial component, aseptic loosening of the tibial component and progression of osteoarthritis in the lateral- and patellofemoral compartment. In five patients a successful reoperation was performed, because of impingement or (sub)luxation of the polyethylene bearing. Patients with a reoperation were significant younger than patients in the primary group (56.7 vs 64.0, P = 0.01) and were more likely to be male (85.7% vs 38.8%, P = 0.015). Overall the cementless medial UKP seems to perform better, but the differences in clinical outcome are not significant; a VAS pain score of 7.4 vs 11.7 (P = 0.22), an Oxford Knee score of 43.3 vs 41.7 (P = 0.27) and a Kujala score of 79.6 vs 78.0 (P = 0.63). The American Knee Society scores were slightly better in the cementless group with 94.5 vs 90.2 (P = 0.055) for the objective score and 91.2 vs 87.8 (P = 0.25) for the subjective score. CONCLUSION: The cementless Oxford phase III medial UKP shows good short-term clinical results, when used in a specialist clinic by an experienced surgeon. PMID:27114932

  13. Costa Rica.

    PubMed

    1989-03-01

    The Republic of Costa Rica is one of the most stable and strongest countries in Central America. It is bordered by Nicaragua and Panama to the north and south and the Caribbean Sea and the Pacific ocean to the east and west and has a total land size slightly smaller than West Virginia. Costa Ricans enjoy a high life expectancy and literacy rate. As well, schools have an attendance rate of nearly 100%. The predominant ethnic group is white, and the predominant spoken language is Spanish. The work force is divided up as follows: 32% agriculture, 25% industry and commerce, 38% services and government, and 5% finance and banking. The country's climate is tropical and subtropical, and the geography of Costa Rica is composed of rugged terrain, mountains, large forest areas, some lowlands and 3 volcanic mountain ranges. The great majority of Costa Ricans are of European descent with only small numbers of the indigenous Indian population surviving today. The government of Costa Rica is democratic, holding periodic elections. The electoral process is monitored by the Supreme Electoral Tribunal. Other bodies of government include the Supreme Court of Justice and the Legislative Assembly. The National Liberation Party has been in power since 1948 and represents socialist ideals. Many factors such as: an influx of enlightened leaders and officials, flexible class lines, economic prosperity and the absence of military force have allowed Costa Rica to progress and maintain a stable economy and government amidst an unstable region. Costa Rica's relations with other countries and international organizations are excellent.

  14. Costa Rica.

    PubMed

    1989-03-01

    The Republic of Costa Rica is one of the most stable and strongest countries in Central America. It is bordered by Nicaragua and Panama to the north and south and the Caribbean Sea and the Pacific ocean to the east and west and has a total land size slightly smaller than West Virginia. Costa Ricans enjoy a high life expectancy and literacy rate. As well, schools have an attendance rate of nearly 100%. The predominant ethnic group is white, and the predominant spoken language is Spanish. The work force is divided up as follows: 32% agriculture, 25% industry and commerce, 38% services and government, and 5% finance and banking. The country's climate is tropical and subtropical, and the geography of Costa Rica is composed of rugged terrain, mountains, large forest areas, some lowlands and 3 volcanic mountain ranges. The great majority of Costa Ricans are of European descent with only small numbers of the indigenous Indian population surviving today. The government of Costa Rica is democratic, holding periodic elections. The electoral process is monitored by the Supreme Electoral Tribunal. Other bodies of government include the Supreme Court of Justice and the Legislative Assembly. The National Liberation Party has been in power since 1948 and represents socialist ideals. Many factors such as: an influx of enlightened leaders and officials, flexible class lines, economic prosperity and the absence of military force have allowed Costa Rica to progress and maintain a stable economy and government amidst an unstable region. Costa Rica's relations with other countries and international organizations are excellent. PMID:12177991

  15. Georgetown University Integrated Community Energy System (GU-ICES). Phase III, Stage I: feasibility analysis. Final report

    SciTech Connect

    Buck, Victor

    1980-10-01

    Candidate energy alternatives are analyzed in Phase III, Stage I, and the appendices are presented for the feasibility analysis. Information in eight appendices includes the following: detailed statement of work; PEPCO rate schedules; cogeneration schemes; added coal, limestone, and ash storage; hot and cold thermal storage; absorption refrigeration; high temperature heat pumps; and life cycle cost analysis. (MCW)

  16. Clinical phase I/II research on ultrasound thermo-chemotherapy in oral and maxillofacial-head and neck carcinoma

    NASA Astrophysics Data System (ADS)

    Shen, Guofeng; Ren, Guoxin; Guo, Wei; Chen, Yazhu

    2012-11-01

    The principle of a ultrasound thermo-chemotherapy instrument and the clinical phase I/II research on short-term and long-term therapeutic effect and main side-effect of ultrasound hyperthermia combined with chemotherapy in oral and maxillofacial-head & neck carcinoma by the instrument will be presented in this paper.

  17. Study of the Need for Educational Manpower for Handicapped Children and Youth: Part A - Phase III. Final Report.

    ERIC Educational Resources Information Center

    Mintz, Raymond D.; And Others

    Phase III of the Study of the Need for Educational Manpower for Handicapped Children and Youth, in demonstrating the feasibility of the Manpower Requirements Projection Model (MRPM), gathered data in the states necessary for implementation of the model. The MRPM was developed to enable state or local administrators of special education to estimate…

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

    SciTech Connect

    O'Neil, Lori Ross; Conway, T. J.; Tobey, D. H.; Greitzer, Frank L.; Dalton, Angela C.; Pusey, Portia K.

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... announced in the May 6, 2013 Federal Register notice (78 FR 26319), and the document now proposes these 28... Deepwater Horizon Oil Spill; Draft Programmatic and Phase III Early Restoration Plan and Draft Early Restoration Programmatic Environmental Impact Statement AGENCY: Interior. ACTION: Notice of...

  20. A Sequenced Instructional Program in Physical Education for the Handicapped, Phase III. Producing and Disseminating Demonstration Packages. Final Report.

    ERIC Educational Resources Information Center

    Carr, Dorothy B.; Avance, Lyonel D.

    Presented is a sequenced instructional program in physical education which constitutes the third of a three-phase, 4-year project, funded by Title III, for handicapped children, preschool through high school levels, in the Los Angeles Unified School District. Described are the project setting and the following accomplishments: a curriculum guide…

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

    SciTech Connect

    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 report

  2. An open, phase III study of lanreotide (Somatuline PR) in the treatment of acromegaly.

    PubMed

    Lin, J D; Lee, S T; Weng, H F

    1999-02-01

    Acromegaly is a disorder caused by excessive secretion of human growth hormone (GH). Somatostatin and its analogue-prolonged release formulation, lanreotide (Somatuline PR), inhibit the secretion of growth hormone. The aim of this open Phase III study was to investigate the clinical efficacy of lanreotide in the treatment of six acromegalic patients with a mean age of 44 +/- 13 yr including two patients with diabetes mellitus. All the patients previously received transsphenoidal or transcranial hypophysectomy. Lanreotide was given intramuscularly every 2 weeks at a fixed dose of 30 mg for 12 weeks. Serum GH and insulin-like growth factor-I (IGF-I) levels were evaluated before, 2, 6 and 12 weeks after treatment. After 12 weeks of treatment, mean (+/- SEM) GH levels decreased from 24.8 +/- 12.5 to 6.9 +/- 3.3 ng/ml and mean serum IGF-I levels decreased from 689 +/- 282 to 430 +/- 216 ng/ml. Abdominal ultrasonographic examinations showed no gallbladder stone or bile sand formation before or after the treatment. Three of the patients who did not receive octreotide presented with manifestations of mild gastrointestinal adverse effect such as mild abdominal pain and diarrhea. In conclusion, lanreotide is effective in the treatment of active postoperative acromegaly. PMID:10426587

  3. Deoxidation of (001) III-V semiconductors in metal-organic vapour phase epitaxy

    NASA Astrophysics Data System (ADS)

    Kaspari, Christian; Pristovsek, Markus; Richter, Wolfgang

    2016-08-01

    We studied the deoxidation of several (001) III-V semiconductors in metal-organic vapour phase epitaxy using in-situ reflectance anisotropy spectroscopy and in-situ spectroscopic ellipsometry. The oxide desorption started as soon as kBT reaches 1/15th of the bond strength of the crystal if there is hydrogen or group V precursor present. The oxide thickness decreases first and afterwards the surface slowly reconstructs. At a constant temperature the oxide thickness decreased according to a second order reaction. We found two processes on InAs and GaAs, but only a single one on InP. The activation energy for the removal of epi-ready oxide under group V flux was 0.64 eV, 1.1 eV, and 1.3 eV on InAs, GaAs, and InP, respectively. The end of oxide desorption is determined by the removal of the last metal rich oxides, at temperatures of 500 °C for InAs/InP and 600 °C for GaAs/GaP.

  4. Design of a phase III clinical trial with prospective biomarker validation: SWOG S0819.

    PubMed

    Redman, Mary W; Crowley, John J; Herbst, Roy S; Hirsch, Fred R; Gandara, David R

    2012-08-01

    The role of cetuximab in the treatment of advanced non-small cell lung cancer (NSCLC) is currently unclear. The molecular target of cetuximab, epidermal growth factor receptor (EGFR), as measured by FISH, has shown potential as a predictive biomarker for cetuximab efficacy in NSCLC. SWOG S0819 is a phase III trial evaluating both the value of cetuximab in this setting and EGFR FISH as a predictive biomarker. This work describes the decision process for determining the design and interim monitoring plan for S0819. Six possible designs were evaluated in terms of their properties and the hypotheses that can be addressed within the design constraints. A subgroup-focused, multiple-hypothesis design was selected for S0819 that incorporates coprimary endpoints to assess cetuximab in both the overall study population and among EGFR FISH-positive (FISH(+)) patients, with the sample size determined based on evaluation in the EGFR FISH(+) group. The chosen interim monitoring plan specifies interim evaluations of both efficacy and futility in the EGFR FISH(+) group alone. The futility-monitoring plan to determine early stopping in the EGFR FISH-nonpositive group is based on evaluation within the positive group, the entire study population, and the nonpositive group. SWOG S0819 uses a design that addresses both the biomarker-driven and general-efficacy objectives of this study.

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

    SciTech Connect

    Bienert, R.W.; Shreffler, D.K.; Word, J.Q.; Kohn, N.P.

    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.

  6. Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma

    PubMed Central

    2014-01-01

    Background Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies. Methods Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups. Results Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests. Conclusion We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients. PMID:24885819

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

    PubMed Central

    Shahtaheri, S.J.; Khadem, M.; Golbabaei, F.; Rahimi-Froushani, A.

    2007-01-01

    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. PMID:19662187

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

    SciTech Connect

    Zheng, Qiye; Kim, Honggyu; Zhang, Runyu; Zuo, Jianmin; Braun, Paul V.; Sardela, Mauro; Balaji, Manavaimaran; Lourdudoss, Sebastian; Sun, Yan-Ting

    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.

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

    SciTech Connect

    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.

  10. Phase I/II Study of Nilotinib/Ruxolitinb Therapy for TKI Resistant Ph-Leukemia

    ClinicalTrials.gov

    2016-03-04

    Chronic Phase Chronic Myeloid Leukemia; Accelerated Phase Chronic Myeloid Leukemia; Blastic Phase Chronic Myeloid Leukemia; Philadelphia Positive Acute Lymphoblastic Leukemia; Resistant to Tyrosine Kinase Inhibitor Therapy

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

    PubMed

    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.

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

    PubMed

    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. PMID:17180414

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

    PubMed Central

    Hu, Xin-Sheng; Hu, Yang

    2015-01-01

    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. PMID:26126177

  14. Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions.

    PubMed

    Dobkin, Bruce H

    2009-01-01

    Based on the suboptimal research pathways that finally led to multicenter randomized clinical trials (MRCTs) of treadmill training with partial body weight support and of robotic assistive devices, strategically planned successive stages are proposed for pilot studies of novel rehabilitation interventions. Stage 1, consideration-of-concept studies, drawn from animal experiments, theories, and observations, delineate the experimental intervention in a small convenience sample of participants, so the results must be interpreted with caution. Stage 2, development-of-concept pilots, should optimize the components of the intervention, settle on most appropriate outcome measures, and examine dose-response effects. A well-designed study that reveals no efficacy should be published to counterweight the confirmation bias of positive trials. Stage 3, demonstration-of-concept pilots, can build out from what has been learned to test at least 15 participants in each arm, using random assignment and blinded outcome measures. A control group should receive an active practice intervention aimed at the same primary outcome. A third arm could receive a substantially larger dose of the experimental therapy or a combinational intervention. If only 1 site performed this trial, a different investigative group should aim to reproduce positive outcomes based on the optimal dose of motor training. Stage 3 studies ought to suggest an effect size of 0.4 or higher, so that approximately 50 participants in each arm will be the number required to test for efficacy in a stage 4, proof-of-concept MRCT. By developing a consensus around acceptable and necessary practices for each stage, similar to CONSORT recommendations for the publication of phase III clinical trials, better quality pilot studies may move quickly into better designed and more successful MRCTs of experimental interventions.

  15. Combining Dosimetry & Toxicity: Analysis of two UK Phase III Clinical trials

    NASA Astrophysics Data System (ADS)

    Gulliford, Sarah L.

    2014-03-01

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

  16. III-nitride nanopyramid light emitting diodes grown by organometallic vapor phase epitaxy

    NASA Astrophysics Data System (ADS)

    Wildeson, Isaac H.; Colby, Robert; Ewoldt, David A.; Liang, Zhiwen; Zakharov, Dmitri N.; Zaluzec, Nestor J.; García, R. Edwin; Stach, Eric A.; Sands, Timothy D.

    2010-08-01

    Nanopyramid light emitting diodes (LEDs) have been synthesized by selective area organometallic vapor phase epitaxy. Self-organized porous anodic alumina is used to pattern the dielectric growth templates via reactive ion etching, eliminating the need for lithographic processes. (In,Ga)N quantum well growth occurs primarily on the six {11¯01} semipolar facets of each of the nanopyramids, while coherent (In,Ga)N quantum dots with heights of up to ˜20 nm are incorporated at the apex by controlling growth conditions. Transmission electron microscopy (TEM) indicates that the (In,Ga)N active regions of the nanopyramid heterostructures are completely dislocation-free. Temperature-dependent continuous-wave photoluminescence of nanopyramid heterostructures yields a peak emission wavelength of 617 nm and 605 nm at 300 K and 4 K, respectively. The peak emission energy varies with increasing temperature with a double S-shaped profile, which is attributed to either the presence of two types of InN-rich features within the nanopyramids or a contribution from the commonly observed yellow defect luminescence close to 300 K. TEM cross-sections reveal continuous planar defects in the (In,Ga)N quantum wells and GaN cladding layers grown at 650-780 °C, present in 38% of the nanopyramid heterostructures. Plan-view TEM of the planar defects confirms that these defects do not terminate within the nanopyramids. During the growth of p-GaN, the structure of the nanopyramid LEDs changed from pyramidal to a partially coalesced film as the thickness requirements for an undepleted p-GaN layer result in nanopyramid impingement. Continuous-wave electroluminescence of nanopyramid LEDs reveals a 45 nm redshift in comparison to a thin-film LED, suggesting higher InN incorporation in the nanopyramid LEDs. These results strongly encourage future investigations of III-nitride nanoheteroepitaxy as an approach for creating efficient long wavelength LEDs.

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

    SciTech Connect

    Sabau, Adrian S

    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

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

    SciTech Connect

    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.

  19. Mono- and polynucleation, atomistic growth, and crystal phase of III-V nanowires under varying group V flow

    SciTech Connect

    Dubrovskii, V. G.

    2015-05-28

    We present a refined model for the vapor-liquid-solid growth and crystal structure of Au-catalyzed III-V nanowires, which revisits several assumptions used so far and is capable of describing the transition from mononuclear to polynuclear regime and ultimately to regular atomistic growth. We construct the crystal phase diagrams and calculate the wurtzite percentages, elongation rates, critical sizes, and polynucleation thresholds of Au-catalyzed GaAs nanowires depending on the As flow. We find a non-monotonic dependence of the crystal phase on the group V flow, with the zincblende structure being preferred at low and high group V flows and the wurtzite structure forming at intermediate group V flows. This correlates with most of the available experimental data. Finally, we discuss the atomistic growth picture which yields zincblende crystal structure and should be very advantageous for fabrication of ternary III-V nanowires with well-controlled composition and heterointerfaces.

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

    SciTech Connect

    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

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

    NASA Technical Reports Server (NTRS)

    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.

  2. A Phase I/II Trial of Topotecan and Radiation Therapy for Brain Metastases in Patients With Solid Tumors

    SciTech Connect

    Hedde, Jan-Peter; Neuhaus, Thomas . E-mail: t.neuhaus@jk-bonn.de; Schueller, Heinrich; Metzler, Ute; Schmidt-Wolf, Ingo G.H.; Kleinschmidt, Rolf; Losem, Christoph; Lange, Oliver; Grohe, Christian; Stier, Sebastian; Ko, Yon-Dschun

    2007-07-01

    Purpose: Outcomes in patients with brain metastases undergoing whole-brain radiotherapy (WBRT) are hardly encouraging, and an improvement in results is therefore needed. One possible approach is the addition of chemotherapeutics. However the data presented thus far are also disappointing. A promising substance in this setting could become topotecan, which is known to cross the blood-brain barrier and additionally offers radiosensitizing effects. Therefore we performed a phase I/II trial to evaluate the feasibility of a concurrent radiochemotherapy regimen. Methods and Materials: From January 1999 to July 2001, a total of 75 patients (10 in phase I and 65 in phase II) were included. The WBRT was applied with a fraction size of 2 Gy/day for a total of 40 Gy. Topotecan was administered as a 30-min infusion with 0.2 to 0.5 mg/m{sup 2}/day for 5 days over 4 weeks within 2 h to radiation therapy. Results: Because of the higher toxic rates seen in patients receiving 0.5 mg/m{sup 2}/day, the recommended dosage for phase II was 0.4 mg/m{sup 2}/day. In this group Grade 3/4 hematologic and nonhematologic side effects occurred in 19% and 21% of the patients, respectively. The overall response rate was 72% with an overall survival of 17 weeks and 30 weeks among the responders. Conclusions: Based on the moderate toxicity profile presented here we recommend to perform a phase III trial to confirm the promising phase I/II data.

  3. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials

    PubMed Central

    Hughes, Derralynn A; Gonzalez, Derlis E; Lukina, Elena A; Mehta, Atul; Kabra, Madhulika; Elstein, Deborah; Kisinovsky, Isaac; Giraldo, Pilar; Bavdekar, Ashish; Hangartner, Thomas N; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-01-01

    Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3–62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2–4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; http://www.clinicaltrials.gov identifier NCT00635427. Am. J. Hematol. 90:584–591, 2015. © 2015 Wiley Periodicals, Inc. PMID:25801797

  4. Effects of gelatin sponge combined with moist wound-healing nursing intervention in the treatment of phase III bedsore

    PubMed Central

    LI, YANLING; YAO, MEIYING; WANG, XIA; ZHAO, YANQING

    2016-01-01

    Pressure sore pertains to tissue damage or necrosis that occurs due to lack of adequate nutrition following long-term exposure to pressure and decreased blood circulation. The aim of the study was to examine the effects of gelatin sponge combined with moist wound-healing nursing intervention in the treatment of phase III bedsore. In total, 50 patients with phase III bedsore were included in the present study. The patients were randomly divided into the control (n=25) and observation (n=25) groups. Patients in the control group received conventional nursing, while those in the observation group received gelatin sponge combined with moist wound healing nursing. The effects of the two nursing methods were compared and analyzed. The results showed that the improvement rate of the observation group was significantly higher than that of the control group (P<0.05). The Branden score and area of pressure sore of the observation group were significantly lower than those of the control group (P<0.05). The frequency and time of dressing change and the average cost of hospitalization of the observation group were significantly lower than those of the control group (P<0.001). In conclusion, gelatin sponge combined with moist wound-healing nursing intervention may significantly improve the treatment of phase III bedsore. PMID:27313666

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

    SciTech Connect

    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.

  6. Certolizumab Pegol Efficacy Across Methotrexate Regimens: A Pre‐Specified Analysis of Two Phase III Trials

    PubMed Central

    Furst, Daniel E.; Keystone, Edward C.; van der Heijde, Désirée; Luijtens, Kristel; Ionescu, Lucian; Goel, Niti; Emery, Paul

    2016-01-01

    Objective Anti–tumor necrosis factor (anti‐TNF) agents are frequently used in combination with methotrexate (MTX) to treat rheumatoid arthritis (RA). We investigated the effect of a background MTX dose, in combination with anti‐TNF certolizumab pegol (CZP), on treatment efficacy and safety in RA patients. Methods A pre‐specified subgroup analysis comparing 2 MTX dosage categories (<15 mg/week and ≥15 mg/week) was carried out using data pooled from phase III clinical trials, Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) and RAPID 2, according to treatment group: CZP 200 mg, CZP 400 mg, or placebo, every 2 weeks. Inclusion criteria required MTX dosage ≥10 mg/week. Efficacy end points included week 24 American College of Rheumatology criteria for 20%, 50%, and 70% improvement (ACR20/50/70) responses analyzed by logistic regression, and changes from baseline in the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) and the modified Sharp/van der Heijde score (SHS) were analyzed by analysis of covariance. Incidence rates of treatment‐emergent adverse events (TEAEs) were categorized by baseline MTX dose. Post hoc sensitivity analysis investigated 3 MTX dose categories: ≤10 mg/week, >10 and ≤15 mg/week, and >15 mg/week. Results A total of 638, 635, and 325 patients received CZP 200 mg, CZP 400 mg, and placebo, respectively. At week 24, treatment responses in both CZP groups were uninfluenced by baseline MTX dose category, and were superior to the placebo group for all investigated end points: ACR20/50/70, DAS28‐ESR, and SHS. TEAE incidence rates were higher in patients receiving MTX ≥15 mg/week for most TEAE types across treatment groups. Conclusion CZP efficacy was not affected by background MTX dose category. It can be hypothesized that to minimize TEAEs, background MTX doses could be tailored to individual patient tolerance without affecting CZP efficacy. PMID:26238672

  7. Magnetic Resonance–Guided Focused Ultrasound for Patients With Painful Bone Metastases: Phase III Trial Results

    PubMed Central

    Ghanouni, Pejman; Kanaev, Sergey V.; Iozeffi, Dmitri; Gianfelice, David; Fennessy, Fiona Mary; Kuten, Abraham; Meyer, Joshua E.; LeBlang, Suzanne D.; Roberts, Ann; Choi, Junsung; Larner, James M.; Napoli, Alessandro; Turkevich, Vladimir G.; Inbar, Yael; Tempany, Clare Mary C.; Pfeffer, Raphael M.

    2014-01-01

    Background Pain due to bone metastases is a common cause of cancer-related morbidity, with few options available for patients refractory to medical therapies and who do not respond to radiation therapy. This study assessed the safety and efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS), a noninvasive method of thermal tissue ablation for palliation of pain due to bone metastases. Methods Patients with painful bone metastases were randomly assigned 3:1 to receive MRgFUS sonication or placebo. The primary endpoint was improvement in self-reported pain score without increase of pain medication 3 months after treatment and was analyzed by Fisher’s exact test. Components of the response composite, Numerical Rating Scale for pain (NRS) and morphine equivalent daily dose intake, were analyzed by t test and Wilcoxon rank-sum test, respectively. Brief Pain Inventory (BPI-QoL), a measure of functional interference of pain on quality of life, was compared between MRgFUS and placebo by t test. Statistical tests were two-sided. Results One hundred forty-seven subjects were enrolled, with 112 and 35 randomly assigned to MRgFUS and placebo treatments, respectively. Response rate for the primary endpoint was 64.3% in the MRgFUS arm and 20.0% in the placebo arm (P < .001). MRgFUS was also superior to placebo at 3 months on the secondary endpoints assessing worst score NRS (P < .001) and the BPI-QoL (P < .001). The most common treatment-related adverse event (AE) was sonication pain, which occurred in 32.1% of MRgFUS patients. Two patients had pathological fractures, one patient had third-degree skin burn, and one patient suffered from neuropathy. Overall 60.3% of all AEs resolved on the treatment day. Conclusions This multicenter phase III trial demonstrated that MRgFUS is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments. PMID:24760791

  8. Breast cancer follow-up strategies in randomized phase III adjuvant clinical trials: a systematic review

    PubMed Central

    2013-01-01

    The effectiveness of different breast cancer follow-up procedures to decrease breast cancer mortality are still an object of debate, even if intensive follow-up by imaging modalities is not recommended by international guidelines since 1997. We conducted a systematic review of surveillance procedures utilized, in the last ten years, in phase III randomized trials (RCTs) of adjuvant treatments in early stage breast cancer with disease free survival as primary endpoint of the study, in order to verify if a similar variance exists in the scientific world. Follow-up modalities were reported in 66 RCTs, and among them, minimal and intensive approaches were equally represented, each being followed by 33 (50%) trials. The minimal surveillance regimen is preferred by international and North American RCTs (P = 0.001) and by trials involving more than one country (P = 0.004), with no relationship with the number of participating centers (P = 0.173), with pharmaceutical industry sponsorship (P = 0.80) and with trials enrolling > 1000 patients (P = 0.14). At multivariate regression analysis, only geographic location of the trial was predictive for a distinct follow-up methodology (P = 0.008): Western European (P = 0.004) and East Asian studies (P = 0.010) use intensive follow-up procedures with a significantly higher frequency than international RCTs, while no differences have been detected between North American and international RCTs. Stratifying the studies according to the date of beginning of patients enrollment, before or after 1998, in more recent RCTs the minimal approach is more frequently followed by international and North American RCTs (P = 0.01), by trials involving more than one country (P = 0.01) and with more than 50 participating centers (P = 0.02). It would be highly desirable that in the near future breast cancer follow-up procedures will be homogeneous in RCTs and everyday clinical settings. PMID:24438135

  9. Safety with Ocrelizumab in Rheumatoid Arthritis: Results from the Ocrelizumab Phase III Program

    PubMed Central

    Emery, Paul; Rigby, William; Tak, Paul P.; Dörner, Thomas; Olech, Ewa; Martin, Carmen; Millar, Laurie; Travers, Helen; Fisheleva, Elena

    2014-01-01

    Objective The objective was to determine the safety of ocrelizumab (OCR) in patients with rheumatoid arthritis (RA). Methods 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. Results 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. Conclusions 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. Trial Registration STAGE Clinical Trials.gov NCT00406419 SCRIPT Clinical Trials.gov NCT00476996 FILM Clinical Trials.gov NCT00485589 FEATURE Clinical Trials.gov NCT00673920 PMID:24498318

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

    PubMed

    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. PMID:26933681

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

    PubMed Central

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

    2016-01-01

    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 (8668412) and six small decahedral cavities (8248) 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. PMID:26933681

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

    PubMed

    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.

  13. Phase equilibrium experiments at 0.5 GPa and 1100 1300 °C on a basaltic andesite from Arenal volcano, Costa Rica

    NASA Astrophysics Data System (ADS)

    Pertermann, Maik; Lundstrom, Craig C.

    2006-09-01

    We present results from piston-cylinder experiments on a synthetic composition of basaltic andesite that corresponds to lavas erupted from the ongoing eruption at Arenal volcano, Costa Rica, in order to shed light on magmatic processes at upper crustal depths beneath Arenal. The starting composition represents the least evolved basaltic andesite from the initiation of stage 2 of the current eruption. Anhydrous and hydrous experiments were conducted at 0.5 GPa and 1100-1300 °C: the principal phases encountered were melt, plagioclase, orthopyroxene and clinopyroxene of variable CaO content. Glass and plagioclase compositions change in a consistent manner with decreasing temperature for both hydrous and anhydrous experiments. The phase equilibria dictate that Arenal magmas must have contained > 2 wt.% H 2O in order for the erupted rocks to have once represented liquid compositions at a relatively high temperature (1200 °C) and > 4 wt.% H 2O if the melt was at the lower temperatures (≤ 1150 °C) that are more likely for the Arenal system. However, anorthite-rich plagioclase phenocrysts (> An 85) commonly found in Arenal lavas cannot be accounted for by any reasonable permutation of higher temperature and water content. The close correspondence of the phase compositions (rims of plagioclase, orthopyroxene) and crystallinity observed in stage 2 lavas from Arenal and a hydrous experiment with 2 wt.% water in the melt provides evidence for Arenal magmas ponding and equilibrating at 1150 °C and ˜ 12-14 km depth. The conclusion that Arenal lavas reflect equilibration between observed minerals and a melt with ˜ 2 wt.% H 2O at 0.5 GPa, ˜ 1150 °C, argues that these bulk compositions are unlikely to have ever reflected fully molten liquids.

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

    PubMed

    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. PMID:21851796

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

    PubMed

    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.

  16. A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer: Phase I Results of RTOG 0117

    SciTech Connect

    Bradley, Jeffrey D.; Moughan, Jennifer; Graham, Mary V.; Byhardt, Roger; Govindan, Ramaswamy; Fowler, Jack; Purdy, James A.; Michalski, Jeff M.; Gore, Elizabeth; Choy, Hak

    2010-06-01

    Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m{sup 2}, and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75%) patients eventually developing grade >=3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients). Conclusions: The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.

  17. ABE Phase III: Progress and Problems. September 1, 1969-April 1, 1970.

    ERIC Educational Resources Information Center

    Southwestern Cooperative Educational Lab., Albuquerque, NM.

    Interim information concerning the ABE III grants is provided in the three parts of this report. Part 1 (outline) describes the goals and objectives of each component; Part 2 describes accomplishments and problems to date; and Part 3 deals with coordination and supervision activities undertaken by the Lab. The components of the program are: (1)…

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

    ClinicalTrials.gov

    2016-04-05

    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

  19. Project NECESSITIES, Phase III. Volume V: Teaching Materials for Second and Third Grades.

    ERIC Educational Resources Information Center

    Abt Associates, Inc., Cambridge, MA.

    Part III, Volume V, Part A of Project NECESSITIES consists of 6 units intended for 2nd-grade American Indian (including Eskimo) children. Activities include music, pantomime, and drama to allow the student and teacher to develop their own classroom version of the story of creation so that the student learns the difference between fact and truth.…

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

    PubMed

    Black, Steven

    2015-01-01

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

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

    PubMed

    Black, Steven

    2015-01-01

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

  2. Randomized Phase III Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Stage III to IV Head and Neck Carcinoma: RTOG 0522

    PubMed Central

    Ang, K. Kian; Zhang, Qiang; Rosenthal, David I.; Nguyen-Tan, Phuc Felix; Sherman, Eric J.; Weber, Randal S.; Galvin, James M.; Bonner, James A.; Harris, Jonathan; El-Naggar, Adel K.; Gillison, Maura L.; Jordan, Richard C.; Konski, Andre A.; Thorstad, Wade L.; Trotti, Andy; Beitler, Jonathan J.; Garden, Adam S.; Spanos, William J.; Yom, Sue S.; Axelrod, Rita S.

    2014-01-01

    Purpose Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Patients and Methods Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Results Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v 2.0%, respectively; P = .81), 3-year PFS (61.2% v 58.9%, respectively; P = .76), 3-year OS (72.9% v 75.8%, respectively; P = .32), locoregional failure (19.9% v 25.9%, respectively; P = .97), or distant metastasis (13.0% v 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v 49.2%, respectively; P < .001) and OS (85.6% v 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Conclusion Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS

  3. Systems Description; Sperry Low Temperature Geothermal Conversion System - Phase I and Phase II; Final Report, Volume III

    SciTech Connect

    Matthews, Hugh B.

    1982-01-01

    This Volume should be considered the introductory volume to the series of six volumes even though numbered out of sequence. Volumes I and II were completed first and released in 1981 while a staff member was available to do the work. Volumes III through VI are being written and released some two years later as DOE funding became available for the purpose. They are as complete as possible considering that almost all the people involved in the program are now unavailable. This Volume III is an overview of the entire program, and many of the items presented herein briefly will be found in expanded form in one of the other five volumes. It will be noticed that assumptions and parameters such as well flow, well temperature, wet bulb temperatures, etc., involved in the several different performance calculations in the volume vary somewhat. These calculations were made at different times for different purposes and no attempt has been made to bring them into exact agreement.

  4. Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study

    PubMed Central

    Chung, Steve S; Fakhoury, Toufic A; Hogan, R Edward; Nagaraddi, Venkatesh N; Blatt, Ilan; Lawson, Balduin; Arnold, Stephan; Anders, Bob; Clark, Annie M; Laine, Dawn; Meadows, R Shawn; Halvorsen, Mark B

    2014-01-01

    Objective To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects. PMID:24902983

  5. Preliminary results of a phase I/II study of sodium pentosanpolysulfate in the treatment of chronic radiation-induced proctitis

    SciTech Connect

    Grigsby, P.W.; Pilepich, M.V.; Parsons, C.L. )

    1990-02-01

    This is a report of a phase I/II study of 13 patients treated with sodium pentosanpolysulfate (PPS) for chronic radiation-induced proctitis. A complete response was obtained in 82%, a partial response occurred in 9%, and 9% failed to respond to therapy. No significant toxicity was observed. It is concluded that PPS is an effective treatment for chronic radiation-induced proctitis and a phase III randomized, double-blind study of PPS versus placebo is planned.

  6. THE PHASES DIFFERENTIAL ASTROMETRY DATA ARCHIVE. III. LIMITS TO TERTIARY COMPANIONS

    SciTech Connect

    Muterspaugh, Matthew W.; Lane, Benjamin F.; Kulkarni, S. R.; Konacki, Maciej; Burke, Bernard F.; Colavita, M. M.; Shao, M. E-mail: blane@draper.co

    2010-12-15

    The Palomar High-precision Astrometric Search for Exoplanet Systems (PHASES) monitored 51 subarcsecond binary systems to evaluate whether tertiary companions as small as Jovian planets orbited either the primary or secondary stars, perturbing their otherwise smooth Keplerian motions. Twenty-one of those systems were observed 10 or more times and show no evidence of additional companions. A new algorithm is presented for identifying astrometric companions and establishing the (companion mass)-(orbital period) combinations that can be excluded from existence with high confidence based on the PHASES observations, and the regions of mass-period phase space being excluded are presented for 21 PHASES binaries.

  7. Costa Rica.

    PubMed

    1992-06-01

    Costa Rica is a country of 51,032 sq. km with 3 million inhabitants, of whom 93% are literate. Independence was gained on September 15, 1821. The terrain consists of eastern and western coastal plains separated by a rugged, central massif, with a climate ranging from tropical to subtropical. Spanish and a Jamaican dialect of English are spoken by European, black, and indigenous ethnic groups who are overwhelmingly of Roman Catholic faith. Life expectancy is approximately 70 years. The gross domestic product is $5.6 billion, growing at a rate of 1%. Per capita income is $1810. Hydroelectric power is a natural resource of the country. Food processing, textiles, construction materials, and fertilizer, as well as banana, coffee, beef, sugarcane, and grain agriculture are areas of economic production. Manufactured goods, machinery, transportation equipment, chemicals, fuel, food, and fertilizer are imported, and bananas, coffee, beef, sugarcane, and grain are exported. In-depth information is also given on the people and history, government and principal officials, political conditions, the economy, defense, foreign relations, relations with the US, and names of principal US officials in the country. PMID:12178043

  8. In-plant demonstration of optimization of energy utilization in beck dyeing of carpet. Proposed Part III, Phase III extension of DOE contract

    SciTech Connect

    1981-01-01

    A proposal to demonstrate on a commercial scale an optimized procedure for beck dyeing of carpet to improve energy utilization is discussed. The proposal is for Phase III. A number of energy conserving procedural and equipment modification including lower dyeing temperature, lower liquor ratio, lower air exhaust flows, and recycle of hot spent dyebaths will be demonstrated in the plant dyeings. Pilot-scale experiments suggest that these modifications will reduce direct energy consumption in carpet dyeing by 400 Btu per pound of carpet processed. Adoption of the modified process by only 50% of the carpet industry would yield an annual reduction in energy consumption of 1 x 10/sup 12/ Btu's (1.7 x 10/sup 5/ BOE). The pilot-scale experiments also indicate that a cost savings of approximately 2 cents per pound of carpet dyed can be achieved with the suggested modifications. The demonstrated technology will have application in other types of nylon and polyester fiber dyeing. The Salem Carpet Mills carpet dyeing facility at Chickamauga, Georgia, will be the site of the demonstration.

  9. ReACT Phase II trial: a critical evaluation of the use of rindopepimut plus bevacizumab to treat EGFRvIII-positive recurrent glioblastoma.

    PubMed

    Gatson, Na Tosha N; Weathers, Shiao-Pei S; de Groot, John F

    2016-01-01

    Glioblastoma is the most deadly primary brain tumor in adults and has long represented a therapeutic challenge. Disease recurrence is inevitable, and the management of recurrent disease is complicated by spontaneous or induced tumor heterogeneity which confers resistance to therapy and increased oncogenicity. EGFR and the tumor-specific mutation EGFRvIII is commonly altered in glioblastoma making it an appealing therapeutic target. Immunotherapy is an emerging and promising therapeutic approach to glioma and the EGFRvIII vaccine, rindopepimut, is the first immunotherapeutic drug to enter Phase III clinical trials for glioblastoma. Rindopepimut activates a specific immune response against tumor cells harboring the EGFRvIII protein. This review evaluates the recently completed ReACT Phase II trial using rindopepimut plus bevacizumab in the setting of EGFRvIII-positive recurrent glioblastoma (Clinical Trials identifier: NCT01498328). PMID:26670466

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

    PubMed

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

    2008-08-15

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

  11. A Phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma

    PubMed Central

    Larkin, J M G; Hughes, S A; Beirne, D A; Patel, P M; Gibbens, I M; Bate, S C; Thomas, K; Eisen, T G; Gore, M E

    2006-01-01

    Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m−2 days 1–5 every 28 days and lomustine 60 mg m–2 on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. PMID:17146474

  12. A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma.

    PubMed

    Larkin, J M G; Hughes, S A; Beirne, D A; Patel, P M; Gibbens, I M; Bate, S C; Thomas, K; Eisen, T G; Gore, M E

    2007-01-15

    Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. PMID:17146474

  13. A Phase I/II adaptive design for heterogeneous groups with application to a stereotactic body radiation therapy trial.

    PubMed

    Wages, Nolan A; Read, Paul W; Petroni, Gina R

    2015-01-01

    Dose-finding studies that aim to evaluate the safety of single agents are becoming less common, and advances in clinical research have complicated the paradigm of dose finding in oncology. A class of more complex problems, such as targeted agents, combination therapies and stratification of patients by clinical or genetic characteristics, has created the need to adapt early-phase trial design to the specific type of drug being investigated and the corresponding endpoints. In this article, we describe the implementation of an adaptive design based on a continual reassessment method for heterogeneous groups, modified to coincide with the objectives of a Phase I/II trial of stereotactic body radiation therapy in patients with painful osseous metastatic disease. Operating characteristics of the Institutional Review Board approved design are demonstrated under various possible true scenarios via simulation studies.

  14. A Phase I/II adaptive design for heterogeneous groups with application to a stereotactic body radiation therapy trial

    PubMed Central

    Wages, Nolan A.; Read, Paul W.; Petroni, Gina R.

    2015-01-01

    Dose-finding studies that aim to evaluate the safety of single agents are becoming less common, and advances in clinical research have complicated the paradigm of dose finding in oncology. A class of more complex problems, such as targeted agents, combination therapies and stratification of patients by clinical or genetic characteristics, has created the need to adapt early-phase trial design to the specific type of drug being investigated and the corresponding endpoints. In this article, we describe the implementation of an adaptive design based on a continual reassessment method for heterogeneous groups, modified to coincide with the objectives of a phase I/II trial of stereotactic body radiation therapy (SBRT) in patients with painful osseous metastatic disease. Operating characteristics of the Institutional Review Board (IRB) approved design are demonstrated under various possible true scenarios via simulation studies. PMID:25962576

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

    PubMed

    Giocos, Georgina; Kagee, Ashraf; Swartz, Leslie

    2008-11-01

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

  16. Sediment Toxicity Identification and Evaluation (TIE) Phases I, II and III Guidance Document

    EPA Science Inventory

    This presentation summarizes the sediment toxicity identification evaluation (TIE) techniques that allow researchers to characterize and identify chemical causes of acute toxicity in sediments that can be applied using the 10-d solid-phase sediment toxicity tests.

  17. III-V on silicon: Observation of gallium phosphide anti-phase disorder by low-energy electron microscopy

    NASA Astrophysics Data System (ADS)

    Döscher, Henning; Borkenhagen, Benjamin; Lilienkamp, Gerhard; Daum, Winfried; Hannappel, Thomas

    2011-08-01

    The formation of anti-phase disorder is a major obstacle in the heteroepitaxy of III-V semiconductors on silicon. For an investigation of the anti-phase domain (APD) structure of GaP/Si(100) samples on mesoscopic length scales, we applied dark-field imaging in a low-energy electron microscope (LEEM) to thin GaP films grown on Si(100) substrates by metal organic vapor phase epitaxy (MOVPE). A contamination-free transfer of the samples from the MOVPE ambient to the ultra-high vacuum chamber of the microscope ensured that the atomically well-ordered, P-rich (2 × 2)/c(4 × 2) reconstruction of the surface was preserved. Mutually perpendicular oriented domains of the characteristic GaP(100) reconstruction identify the APDs in the GaP film at the surface and enabled us to achieve high contrast LEEM images. Striped patterns of APDs reflect the regular terrasse structure of the two-domain Si(100)(2 × 1) substrate far away from defects. APDs in the proximity of the defects have larger lateral extensions and are arranged in target pattern-like structures around the defects. In contrast to transmission electron microscopy, which was also applied in a specific dark-field mode for comparison, the characterization of anti-phase disorder by LEEM is non-destructive, does not require elaborate sample preparation, and addresses extended length scales.

  18. Crystal structure and investigation of phase transitions in hexa (2 amino-indolinium) dodécachlorobithallate(III) and quinolinium tetrachlorothallate(III)

    NASA Astrophysics Data System (ADS)

    Chaari, Najla; Hamdi, Besma; Chaabouni, Slaheddine; Chniba-Boudjada, Nassira; Bordet, Pierre

    2007-12-01

    Two new thallium containing salts with different aryl ammonium cations have been prepared and characterized by X-ray crystallography, infrared spectroscopy and dielectric measurements. The salt [C 8N 2H 8] 6Tl 2Cl 12 (1) crystallizes in the monoclinic system with space group Pn. The unit cell dimensions are: a = 15.120(5), b = 11.825(5), c = 17.167(5) Å, β = 104.460(5)° with Z = 2, Dcalcd = 1.818 g cm -3, R = 0.0369. The structure consists of 2 amino-indolinium cations and monomeric TlCl63- anions. The TlCl63- has a strongly octahedral geometry presenting five short and one long (Tl1-Cl13 = 2.739(5) and Tl2-Cl26 = 2.684(5) Å) Tl-Cl bonds. The presence of multiple hydrogen bonds is considered to be responsible for the octahedral distortion. However, the second compound [C 9H 8N]TlCl 4 (2) crystallizes in the Pna2 1 orthorhombic space group, with a = 9.253(1), b = 9.799(1), c = 14.558(2) Å, Z = 4, Dcalcd = 2.397 g cm -3, R = 0.0608. The structure of the quinolinium tetrachlorothallate(III) is characterized by tetracoordinate thallium, forming a regular tetrahedral TlCl 4 with Tl-Cl distances between 2.366(2) and 2.451(3) Å. The structure consists of quinolinium cations separating chains of TlCl4- tetrahedra, these chains being perpendicular to the c axis. Infrared spectra confirm the presence of the organic cations. Differential scanning calorimetry study was carried out. Electrical measurements were performed to discuss the mechanism of the phase transition.

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

    SciTech Connect

    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.

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

    SciTech Connect

    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.

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

    SciTech Connect

    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.

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

    SciTech Connect

    1999-01-01

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

  3. Selective solid-phase extraction and analysis of trace-level Cr(III), Fe(III), Pb(II), and Mn(II) Ions in wastewater using diethylenetriamine-functionalized carbon nanotubes dispersed in graphene oxide colloids.

    PubMed

    Zhu, Xiangbing; Cui, Yuemei; Chang, Xijun; Wang, Hua

    2016-01-01

    Multi-walled carbon nanotubes (MCNTs) were dispersed in graphene oxide (GO) colloids to be further functionalized with diethylenetriamine (DETA), resulting in GO-MCNTs-DETA nanocomposites for the solid-phase extraction and analysis of Cr(III), Fe(III), Pb(II), and Mn(II) ions at the trace levels in wastewater. Inductively coupled plasma optical emission spectrometry (ICP-OES) indicates that this new solid-phase sorbent could facilitate the maximum static adsorption capacities of 5.4, 13.8, 6.6 and 9.5 mg g(-1) for Cr(III), Fe(III), Pb(II), and Mn(II) ions, respectively, showing the adsorption capacity up to 95% within about 30 min. Moreover, the detection limits of the GO-MCNTs-DETA-based analysis method were found to be 0.16, 0.50, 0.24 and 0.38 ng mL(-1) for Cr(III), Fe(III), Pb(II), and Mn(II) ions, respectively, with the relative standard deviation of lower than 3.0% (n=5). Importantly, common coexisting ions showed no significant interference on the separation and pre-concentration of these heavy metal ions at pH 4.0. Subsequently, the GO-MCNTs-DETA sorbent was successfully employed for the separation and analysis of trace-level Cr(III), Fe(III), Pb(II), and Mn(II) ions in wastewater samples yielding 75-folds concentration factors. PMID:26695275

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

    SciTech Connect

    Zhang, Jin S. Bass, Jay D.; Shieh, Sean R.; Dera, Przemyslaw; Prakapenka, Vitali

    2014-04-07

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

  5. Confirmation of model-based dose selection for a Japanese phase III study of rivaroxaban in non-valvular atrial fibrillation patients.

    PubMed

    Kaneko, Masato; Tanigawa, Takahiko; Hashizume, Kensei; Kajikawa, Mariko; Tajiri, Masahiro; Mueck, Wolfgang

    2013-01-01

    This study was designed to confirm the appropriateness of the dose setting for a Japanese phase III study of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), which had been based on model simulation employing phase II study data. The previously developed mixed-effects pharmacokinetic/pharmacodynamic (PK-PD) model, which consisted of an oral one-compartment model parameterized in terms of clearance, volume and a first-order absorption rate, was rebuilt and optimized using the data for 597 subjects from the Japanese phase III study, J-ROCKET AF. A mixed-effects modeling technique in NONMEM was used to quantify both unexplained inter-individual variability and inter-occasion variability, which are random effect parameters. The final PK and PK-PD models were evaluated to identify influential covariates. The empirical Bayes estimates of AUC and C(max) from the final PK model were consistent with the simulated results from the Japanese phase II study. There was no clear relationship between individual estimated exposures and safety-related events, and the estimated exposure levels were consistent with the global phase III data. Therefore, it was concluded that the dose selected for the phase III study with Japanese NVAF patients by means of model simulation employing phase II study data had been appropriate from the PK-PD perspective. PMID:23337693

  6. Development of a "First-Principles" Water Potential with Flexible Monomers. III. Liquid Phase Properties.

    PubMed

    Medders, Gregory R; Babin, Volodymyr; Paesani, Francesco

    2014-08-12

    The MB-pol full-dimensional water potential introduced in the first two papers of this series [J. Chem. Theory Comput. 2013, 9, 5395 and J. Chem. Theory Comput. 2014, 10, 1599] is employed here in classical and quantum simulations of liquid water under ambient conditions. Comparisons with the available experimental data for several structural, thermodynamic, and dynamical properties indicate that MB-pol provides a highly accurate description of the liquid phase. Combined with previous analyses of the dimer vibration-rotation tunneling spectrum, second and third virial coefficients, and cluster structures and energies, the present results demonstrate that MB-pol represents a major step toward the long-sought "universal model" capable of describing the properties of water from the gas to the condensed phases.

  7. Phase Stability of Chromium(III) Oxide Hydroxide in Alkaline Sodium Phosphate Solutions

    SciTech Connect

    S.E. Ziemniak; E.P. Opalka

    2003-07-08

    Grimaldiite ({alpha}-CrOOH) is shown to transform to a sodium-chromium(III)-hydroxyphosphate compound (SCHP) in alkaline sodium phosphate solutions at elevated temperatures via CrOOH(s) + 4Na{sup +} + 2HPO{sub 4}{sup 2-} = Na{sub 4}Cr(OH)(PO{sub 4}){sub 2}(s) + H{sub 2}O. X-ray diffraction analyses indicate that SCHP possesses an orthorhombic lattice having the same space group symmetry (Ibam, No.72) as sodium ferric hydroxyphosphate. A structurally-consistent designation for SCHP is Na{sub 3}Cr(PO{sub 4}){sub 2} {center_dot} NaOH; the molar volume of SCHP is estimated to be 1552 cm{sup 3}. The thermodynamic equilibrium for the above reaction was defined in the system Na{sub 2}O-P{sub 2}O{sub 5}-Cr{sub 2}O{sub 3}-H{sub 2}O for Na/P molar ratios between 2.0 and 2.4. On the basis of observed reaction threshold values for sodium phosphate concentration and temperature, the standard molar entropy (S{sup o}), heat capacity (C{sub p}{sup o}) and free energy of formation ({Delta}G{sub f}{sup o}) for SCHP were calculated to be 690 J/(mol-K), 622 J/(mol-K) and -3509.97 kJ/mol, respectively.

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

    NASA Technical Reports Server (NTRS)

    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.

  9. Phase 0/I/II Cancer Prevention Clinical Trials Program (Consortia) | Division of Cancer Prevention

    Cancer.gov

    Five cancer research centers lead multiple collaborative networks to assess potential cancer preventive agents and to conduct early clinical development of promising preventive agents. Also called the Consortia for Early Phase Prevention Trials, the studies require extensive biomarker analysis, investigation of the biologic effects of the cancer preventive agents on their intended molecular targets and on multiple endpoints associated with carcinogenesis, and correlation with clinically relevant endpoints.  | Systematic early clinical development of promising preventive agents through five major medical research centers.

  10. A phase I/II trial of BNC105P with everolimus in metastatic renal cell carcinoma (mRCC)

    PubMed Central

    Pal, Sumanta; Azad, Arun; Bhatia, Shailender; Drabkin, Harry; Costello, Brian; Sarantopoulos, John; Kanesvaran, Ravindran; Lauer, Richard; Starodub, Alexander; Hauke, Ralph; Sweeney, Christopher J.; Hahn, Noah M.; Sonpavde, Guru; Richey, Stephen; Breen, Timothy; Kremmidiotis, Gabriel; Leske, Annabell; Doolin, Elizabeth; Bibby, David C.; Simpson, Jeremy; Iglesias, Jose; Hutson, Thomas

    2015-01-01

    Purpose BNC105P inhibits tubulin polymerization, and preclinical studies suggest possible synergy with everolimus. In this phase I/II study, efficacy and safety of the combination were explored in patients with metastatic renal cell carcinoma (mRCC). Experimental Design A phase I study in patients with clear cell mRCC and any prior number of therapies was conducted using a classical 3+3 design to evaluate standard doses of everolimus with increasing doses of BNC105P. At the recommended phase II dose (RP2D), patients with clear cell mRCC and 1-2 prior therapies (including ≥1 VEGF-TKI) were randomized to BNC105P with everolimus (Arm A) or everolimus alone (Arm B). The primary endpoint of the study was 6-month progression-free survival (6MPFS). Secondary endpoints included response rate, PFS, overall survival (OS) and exploratory biomarker analyses. Results In the phase I study (n=15), a dose of BNC105P at 16 mg/m2 with everolimus at 10 mg daily was identified as the RP2D. In the phase II study, 139 patients were randomized, with 69 and 67 evaluable patients in Arms A and B, respectively. 6MPFS was similar in the treatment arms (Arm A: 33.82% v Arm B: 30.30%, P=0.66) and no difference in median PFS was observed (Arm A: 4.7 mos v Arm B: 4.1 mos; P=0.49). Changes in matrix metalloproteinase-9, stem cell factor, sex hormone binding globulin and serum amyloid A protein were associated with clinical outcome with BNC105P. Conclusions Although the primary endpoint was not met in an unselected population, correlative studies suggest several biomarkers that warrant further prospective evaluation. PMID:25788492

  11. Phase I/II study of 131I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma

    PubMed Central

    DuBois, S G; Allen, S; Bent, M; Hilton, J F; Hollinger, F; Hawkins, R; Courtier, J; Mosse, Y P; Matthay, K K

    2015-01-01

    Background: 131I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan. Methods: Patients 1–30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days −1 to +6, irinotecan (50 mg m−2 per dose IV) on days 0–4, vincristine (2 mg m−2) on day 0, MIBG (555 or 666 MBq kg−1) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients. Results: Thirty-two patients (12 phase I ; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg−1. Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80% vs 37% P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients. Conclusions: MIBG (666 MBq kg−1) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan. PMID:25602966

  12. The effects of PECS teaching to Phase III on the communicative interactions between children with autism and their teachers.

    PubMed

    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.

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

    SciTech Connect

    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.

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

    SciTech Connect

    Leitzinger, Eric J.

    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.

  15. Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

    PubMed

    Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D

    2015-03-24

    Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist. PMID:25681064

  16. Phase III trial comparing two low dose rates in brachytherapy of cervix carcinoma: Report at two years

    SciTech Connect

    Lambin, P.; Gerbaulet, A.; Kramer, A.; Haie-Meder, C.; Malaise, E.P.; Chassagne, D. ); Scalliet, P. )

    1993-02-15

    This Phase III randomized trial examined the effect of two low dose rates (0.73 or 0.38 Gy[center dot]h[sup [minus]1]) on the local control, survival, relapse-free survival, complications, and secondary effects in the treatment of cervical cancers. A total of 204 Stage Ib or II cervical carcinoma patients were included between January 1985 and September 1988. Treatment consisted of uterovaginal [sup 137]Cs irradiation followed by surgery. The two groups were similar for age, tumor stage and medical or surgical history. Their brachytherapy parameters were also similar (60 Gy pear dimensions, dose to critical organs, total kerma, etc....). There were no differences in the short-term effects or therapeutic outcome. However, overall complications and side effects observed after 6 months were significantly more frequent (p < 0.01) in the higher dose rate group. 40 refs., 4 figs., 6 tabs.

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

    SciTech Connect

    Ivanova, T.; Laville, C.; Dyrda, J.; Mennerdahl, D.; Golovko, Y.; Raskach, K.; Tsiboulia, A.; Lee, G. S.; Woo, S. W.; Bidaud, A.; Sabouri, P.; Bledsoe, K.; Rearden, B.; Gulliford, J.; Michel-Sendis, F.

    2012-07-01

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

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

    PubMed

    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.

  19. Phase I/II Clinical Evaluation of StrataGraft: A Consistent, Pathogen-Free Human Skin Substitute

    PubMed Central

    Schurr, Michael J.; Foster, Kevin N.; Centanni, John M.; Comer, Allen R.; Wicks, April; Gibson, Angela L.; Thomas-Virnig, Christina L.; Schlosser, Sandy J.; Faucher, Lee D.; Lokuta, Mary A.; Allen-Hoffmann, B. Lynn

    2009-01-01

    Background Large wounds often require temporary allograft placement to optimize the wound bed and prevent infection until permanent closure is feasible. We developed and clinically tested a second-generation living human skin substitute (StrataGraft). StrataGraft provides both a dermis and a fully-stratified, biologically-functional epidermis generated from a pathogen-free, long-lived human keratinocyte progenitor cell line, Neonatal Immortalized KeratinocyteS (NIKS). Methods Histology, electron microscopy, quantitative polymerase chain reaction, and bacterial growth in vitro were used to analyze human skin substitutes generated from primary human keratinocytes or NIKS cells. A phase I/II, National Institute of Health-funded, randomized, safety, and dose escalation trial was performed to assess autograft take in 15 patients 2 weeks after coverage with StrataGraft skin substitute or cryopreserved cadaver allograft. Results StrataGraft skin substitute exhibited a fully stratified epidermis with multilamellar lipid sheets and barrier function as well as robust human β defensin-3 mRNA levels. Analysis of the primary endpoint in the clinical study revealed no differences in autograft take between wound sites pretreated with StrataGraft skin substitute or cadaver allograft. No StrataGraft-related adverse events or serious adverse events were observed. Conclusions The major finding of this phase I/II clinical study is that performance of StrataGraft skin substitute was comparable to cadaver allograft for the temporary management of complex skin defects. StrataGraft skin substitute may also eliminate the risk for disease transmission associated with allograft tissue and offer additional protection to the wound bed through inherent antimicrobial properties. StrataGraft is a pathogen-free human skin substitute that is ideal for the management of severe skin wounds before autografting. PMID:19276766

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

    PubMed

    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

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

    SciTech Connect

    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.

  2. Vapor phase growth technique of III-V compounds utilizing a preheating step

    NASA Technical Reports Server (NTRS)

    Olsen, Gregory Hammond (Inventor); Zamerowski, Thomas Joseph (Inventor); Buiocchi, Charles Joseph (Inventor)

    1978-01-01

    In the vapor phase epitaxy fabrication of semiconductor devices and in particular semiconductor lasers, the deposition body on which a particular layer of the laser is to be grown is preheated to a temperature about 40.degree. to 60.degree. C. lower than the temperature at which deposition occurs. It has been discovered that by preheating at this lower temperature there is reduced thermal decomposition at the deposition surface, especially for semiconductor materials such as indium gallium phosphide and gallium arsenide phosphide. A reduction in thermal decomposition reduces imperfections in the deposition body in the vicinity of the deposition surface, thereby providing a device with higher efficiency and longer lifetime.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  4. Fluid flow through a vertical to horizontal 90 elbow bend III three phase flow

    SciTech Connect

    Spedding, P.L.; Benard, E.; Crawford, N.M.

    2008-01-15

    Three phase water/oil/air flow was studied around a vertical upward to horizontal 90 elbow bend of R/d = 0.654. The results were more complex than corresponding two phase data. The pressure drop recorded for the two tangent legs sometimes showed significant variations to the straight pipe data. In most cases this variation was caused by differences in the flow regimes between the two systems. The elbow bend tended to constrict the flow presented by the vertical inlet tangent leg while sometimes acting as a wave and droplet generator for the horizontal outlet tangent leg. It could be argued that the inclusion of the elbow bend altered the flow regime map transitional boundaries but it also is possible that insufficient settling length was provided in the apparatus design. The elbow bend pressure drop was best presented as l{sub e}/d the equivalent length to diameter ratio using the actual total pressure drop in the vertical inlet tangent leg. Generally l{sub e}/d values rose with gas rate, but exhibited an increasingly complex relation with f{sub o} the oil to liquid volumetric ratio as liquid rate was increased. A significant maximum in l{sub e}/d was in evidence around the inversion from water dominated to oil dominated flows. Several models are presented to predict the data. (author)

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

    PubMed Central

    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

  6. Phase Behavior of Nematic-Nonnematic Binary Systems: III. The Effect of Hydrogen Bonding Interaction

    NASA Astrophysics Data System (ADS)

    Asaba, Kazunori; Igarashi, Atsuko; Kobinata, Shunsuke

    1998-12-01

    For the binary mixtures of nematic 4-pentyl-4‧-cyanobiphenyl (5CB) with some kinds of nonnematic solutes, which showed `unusual' increase in nematic-isotropic phase transition temperature compared with that of pure 5CB, we have measured the temperature dependence of the IR dichroic ratio for several bands of 5CB and of the solutes. The dichroic ratios and their temperature dependence distinctly showed the presence of rather firmly hydrogen-bonded complexes in these binary systems. We found some interesting results, e.g., the dichroic ratios for the OH stretching mode of phenol, which is hydrogen bonded to the CN group of 5CB, and for p-ethyl benzoic acid were larger than the dichroic ratio of the CN band. The temperature dependence of the second-order parameters derived from IR dichroic ratios was analyzed based on a Maier-Saupe-type mean field theory.

  7. 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.

    PubMed

    Jiang, Hongmei; Hu, Bin; Chen, Beibei; Xia, Linbo

    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 0.12ngmL(-1) with enrichment factor of 78 was achieved. The relative standard deviation (R.S.D.) of the method for five replicate determinations of 5ngmL(-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. PMID:19154804

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

    PubMed

    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.

  9. Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke: Results of a Prematurely Terminated Randomized Clinical Trial

    PubMed Central

    Haley, E. Clarke; Thompson, John L.P.; Grotta, James C.; Lyden, Patrick D.; Hemmen, Thomas G.; Brown, Devin L.; Fanale, Christopher; Libman, Richard; Kwiatkowski, Thomas G.; Llinas, Rafael H.; Levine, Steven R.; Johnston, Karen C.; Buchsbaum, Richard; Levy, Gilberto; Levin, Bruce

    2010-01-01

    Background: Intravenous alteplase (rt-PA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to a) choose a best dose of tenecteplase to carry forward, and b) to provide evidence for either promise or futility of further testing of tenecteplase versus rt-PA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rt-PA. Methods: The trial began as a small, multi-center, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rt-PA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24 hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage (ICH) to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rt-PA could be compared by 3 month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. Results: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4 mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3 month outcomes between the remaining tenecteplase groups and rt-PA. Symptomatic ICH rates were highest in the

  10. Rapid speciation analysis of Cr(VI) and Cr(III) by reversed-phase high-performance liquid chromatography with UV detection.

    PubMed

    Hossain, Mohammad Abul; Kumita, Mikio; Michigami, Yoshimasa; Islam, Tajmeri S A; Mori, Shigeru

    2005-02-01

    A simple and rapid method is developed for the simultaneous determination of Cr(VI) and Cr(III) based on the formation of their different complexes with ammonium pyrrolidine-dithiocarbamate (APDC). Separation is performed using reversed-phase high-performance liquid chromatography coupled with UV detection. The conditions for complex formation and speciation are determined, such as solution pH, amount of APDC, temperature, and type of mobile phase. In order to substantially reduce the analysis time, the separation is carried out without extraction of chromium-APDC complexes from the mother liquor. Under the optimum analysis conditions, the chromatograms obtained show good peak separation, and the absolute detection limits (3s) are 2.2 microg/L for Cr(VI) and 4.5 microg/L for Cr(III). The calibration curves are linear from 3 to 5000 microg/L for Cr(VI) and 5 to 3000 microg/L for Cr(III). The relative standard deviations of peak areas in five measurements using a sample solution of 200 microg/L are less than 2% for Cr(VI) and 4% for Cr(III), indicating good reproducibility for this analytical method. Furthermore, simultaneous determination of Cr(VI) and Cr(III) is successful with the application of the proposed procedure in the synthetic wastewaters containing common heavy metal ions: Fe(III), Pb(II), Cd(II), Cu(II), and Zn(II). PMID:15826369

  11. ASSESSMENT OF SUBSURFACE FATE OF MONOETHANOLAMINE AT SOUR GAS PROCESSING PLANT SITES-PHASE III

    SciTech Connect

    James A. Sorensen

    1999-02-01

    Alkanolamines are commonly used by the natural gas industry to remove hydrogen sulfide, carbon dioxide, and other acid gases from the natural gas in which they occur (''sour'' gas if hydrogen sulfide is present). At sour gas-processing plants, as at all plants that use alkanolamines for acid gas removal (AGR), spills and on-site management of wastes containing alkanolamines and associated reaction products have occasionally resulted in subsurface contamination that is presently the focus of some environmental concern. In 1994, the Energy and Environmental Research Center (EERC) initiated a three-phase program to investigate the natural attenuation processes that control the subsurface transport and fate of the most commonly used alkanolamine in Canada, monoethanolamine (MEA). Funding for the MEA research program was provided by the U.S. Department of Energy (DOE), Canadian Association of Petroleum Producers (CAPP), Canadian Occidental Petroleum Ltd. (CanOxy), Gas Research Institute (GRI), Environment Canada, and the National Energy Board of Canada. The MEA research program focused primarily on examining the biodegradability of MEA and MEA-related waste materials in soils and soil-slurries under a variety of environmentally relevant conditions, evaluating the mobility of MEA in soil and groundwater and the effectiveness of bioremediation techniques for removing contaminants and toxicity from MEA-contaminated soil. The presently inactive Okotoks sour gas-processing plant, owned by CanOxy in Alberta, Canada, was the source of samples and field data for much of the laboratory-based experimental work and was selected to be the location for the field-based efforts to evaluate remediation techniques. The objective of the research program is to provide the natural gas industry with ''real world'' data and insights developed under laboratory and field conditions regarding the effective and environmentally sound use of biological methods for the remediation of soil

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

    SciTech Connect

    Neeraj Gupta

    2006-01-23

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

  13. Advanced heat pump for recovery of volatile organic compounds, Phase III - demonstration of BCSRHP mobile regenerator. Final report

    SciTech Connect

    Not Available

    1994-11-01

    Under Phase I of the subject contract, feasibility studies and basic engineering studies were performed for a Brayton Cycle Solvent Recovery Heat Pump (BCSRBP) system to prevent pollution from small source emitters. It was determined that the cost of a complete system, including adsorbers and regeneration process, would be far too much for the small emission source in most cases. This {open_quotes}integrated{close_quotes} approach was therefore not feasible. However, it was concluded that the expensive portion of the Brayton cycle process, the regenerator, could be shared by mounting it on a trailer that could be transported to different sites to regenerate an adsorber. Under Phase II of the project a mobile regenerator (BCSRI-IP) was designed and built to serve a large number of sites. Adsorbers were designed to control emissions for a week or more between regenerations. The purpose of phase III was to demonstrate the cost effectiveness and efficiency of the shared (decoupled) BRAYSORB{reg_sign} solvent recovery system in energy use and emission control compared to other control technologies through a performance testing program at representative industrial and commercial host sites in Southern California. NUCON was the prime contractor for the demonstration portion of this project. Support and funding were received from Southern California Edison Company, South Coast Air Quality Management District, and the U.S. Department of Energy in addition to the contribution by NUCON. Contractual arrangements were completed with each of the host sites and permits for both the stationary and mobile equipment were acquired. The adsorbers were installed at each host site and the appropriate interface connections were made. The mobile regenerator was transported to Southern California for the demonstration.

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

    PubMed Central

    2012-01-01

    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 New Drug Application

  15. A National Study of Internal Medicine--Phase III. Analysis of 1976-1977 Resident Cohort Currently in Practice. Final Report.

    ERIC Educational Resources Information Center

    Schleiter, Mary Kay; Tarlov, Alvin R.

    The different practice styles of young internists and the relationship between training and practice were studied as part of the National Study of Internal Medicine Manpower, Phase III. The practices of four groups of physicians were compared: general internists with traditional residencies, general internists who received their residency training…

  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

    SciTech Connect

    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. Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial.

    PubMed

    Miller, R L; Bukowski, R M; Budd, G T; Purvis, J; Weick, J K; Shepard, K; Midha, K K; Ganapathi, R

    1988-05-01

    Drug resistance to chemotherapy agents such as doxorubicin appears to be an important cause of therapeutic failure in cancer treatment. Based on preclinical information demonstrating that the phenothiazine calmodulin-inhibitor trifluoperazine can enhance retention and cytotoxicity of doxorubicin in resistant cells, a phase I/II trial of the combination was performed to determine the maximally tolerated dose (MTD) of trifluoperazine that could be administered with doxorubicin. Patients with intrinsic (no previous response) and acquired (previous response with relapse) doxorubicin resistance were eligible. Doxorubicin was administered as a 96-hour continuous infusion (60 mg/m2) on days 2 through 5. Trifluoperazine was administered in divided doses orally on days 1 through 6, with dose escalation from 20 to 100 mg/d. Thirty-six patients were evaluable. The MTD of trifluoperazine was 60 mg/d, with dose-limiting toxicity being extrapyramidal side effects. No alteration of doxorubicin toxicity was observed. Seven of the 36 patients responded (one complete response [CR], six partial responses [PR]), with seven of 21 patients having acquired resistance, and zero of 15 with intrinsic resistance demonstrating responses. Doxorubicin plasma levels were not affected by trifluoperazine, and the maximal trifluoperazine plasma levels achieved were 129.83 ng/mL. This trial demonstrates the combination of trifluoperazine and doxorubicin is well tolerated, and the schedule recommended for phase II trials is doxorubicin, 60 mg/m2 (continuous infusion) days 2 through 5, and trifluoperazine, 15 mg four times per day orally days 1 through 6. Continued investigation of this combination is indicated for patients with acquired doxorubicin resistance.

  18. Three Phase III Randomized Controlled Trials of Topical Resiquimod 0.01-Percent Gel To Reduce Anogenital Herpes Recurrences

    PubMed Central

    Spruance, Spotswood; Kinghorn, George R.; Sacks, Stephen L.; Slade, Herbert B.; Meng, Tze-Chiang; Selke, Stacy; Magaret, Amalia; Wald, Anna

    2014-01-01

    Resiquimod, a Toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed posttreatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ≥4 recurrences within the prior year. Participants applied resiquimod 0.01% gel or vehicle gel 2 times per week for 3 weeks to each recurrence for 12 months. Trials 1 and 2 had 2:1 resiquimod-vehicle randomization. Trial 3 had 1:1:1 randomization for resiquimod and 500 mg valacyclovir orally twice daily for 5 days (RESI-VAL), resiquimod and oral placebo (RESI-PLA), and vehicle and oral placebo (VEH-PLA). The median time to first recurrence was similar for resiquimod and vehicle (trial 1, 60 and 56 days, P = 0.7; trial 2, 54 and 48 days, P = 0.47; trial 3, 51 [RESI-VAL], 55 [RESI-PLA], and 44 [VEH-PLA] days, P = not significant [NS]). The median time to healing of initial treated recurrence was longer for resiquimod (trial 1, 18 compared to 10 days, P < 0.001; trial 2, 19 compared to 13 days, P = 0.16; trial 3, 14 [RESI-VAL], 16 [RESI-PLA], and 8 [VEH-PLA] days, P < 0.001). In trials 1 and 2, moderate to severe erythema and erosion/ulceration at the application site were more common in resiquimod recipients. In conclusion, no posttreatment efficacy of resiquimod 0.01% gel was observed. Increased application site reactions and initial recurrence healing time are consistent with resiquimod-induced cytokine effects. PMID:24709264

  19. Intravitreal Sirolimus for the Treatment of Geographic Atrophy: Results of a Phase I/II Clinical Trial

    PubMed Central

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

    2015-01-01

    Purpose. To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). Methods. The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Results. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. Conclusions. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.) PMID:25525171

  20. A Phase I/II Trial of Gefitinib Given Concurrently With Radiotherapy in Patients With Nonmetastatic Prostate Cancer

    SciTech Connect

    Joensuu, Greetta; Joensuu, Timo; Nokisalmi, Petri

    2010-09-01

    Purpose: To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer. Methods and Materials: A total of 42 patients with T2-T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0-1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day) was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1{alpha} (IL-1{alpha}), and IL-6 in serum. Results: Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses. Conclusions: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.

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

    SciTech Connect

    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.

  2. Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: A randomized placebo-controlled phase III study

    SciTech Connect

    Buentzel, Jens . E-mail: jens.buentzel@shk-ndh.de; Micke, Oliver; Adamietz, Irenaus A.; Monnier, Alain; Glatzel, Michael; Vries, Alexander de

    2006-03-01

    Purpose: Clinical trials demonstrated the efficacy and safety of intravenous (i.v.) or subcutaneous (s.c.) amifostine for reducing xerostomia and mucositis after radiotherapy or radiochemotherapy for head-and-neck cancer. This randomized, double-blinded, placebo-controlled, phase III study evaluated the efficacy and safety of i.v. amifostine during radiochemotherapy for head-and-neck cancer. Methods and Materials: Patients from European and American study centers received i.v. amifostine 300 mg/m{sup 2} (n = 67) or placebo (n = 65) before carboplatin 70 mg/m{sup 2} and radiotherapy on Days 1 to 5 and 21 to 25, and i.v. amifostine 200 mg/m{sup 2} or placebo before radiotherapy on other days. Results: Toxicity incidences were (amifostine, placebo, p value): Grade 2 or higher acute xerostomia (39%, 34%, 0.715), Grade 3 or higher acute mucositis (39%, 22%, 0.055), Grade 2 or higher late xerostomia (37%, 24%, 0.235), and Grade 3 or higher treatment-related adverse events (42%, 20%, 0.008). One-year rates of locoregional failure, progression-free survival, and overall survival were not significantly different between treatments. Conclusions: The used amifostine doses were not able to reduce the toxicity of simultaneous radiochemotherapy for head-and-neck cancer. The safety of amifostine and the lack of tumor protection were consistent with previous studies.

  3. Ethical issues in pediatric oncology phase I-II trials based on a mother's point of view.

    PubMed

    Oppenheim, D; Geoerger, B; Hartmann, O

    2005-11-01

    Phase I-II trials are developing in Pediatrics and raise many complex relational, psychological and ethical issues. We present and discuss these based on an interview in a pediatric oncology setting, with a mother who accepted that her daughter be included in such trials and who expressed why she accepted with great sensitivity and profoundness. She explained that after many years of inefficient treatments she had lost all her landmarks and was ready to accept any proposition, even those she would have considered unacceptable earlier. She did not know whether there is a limit to what is acceptable. Her only objective was to gain any time possible in order to continue living with her daughter. She found it important that the research doctor be different from the doctor involved in patient care, and that the latter remains the major decision-maker and correspondent: thus the child's best interests take precedence over that of research. Interviews with the psycho-oncologist can help the parents and the doctors gain a better insight into the various aspects, rational and irrational, conscious and unconscious, involved in the proposition to participate in a clinical trial and in the parents' or the child's acceptance or refusal.

  4. Ovarian Transcriptome Analysis of Portunus trituberculatus Provides Insights into Genes Expressed during Phase III and IV Development

    PubMed Central

    Han, Tao; Liu, Tao; Wang, Chunlin; Xiao, Jia; Mu, Changkao; Li, Ronghua; Yu, Fangping; Shi, Huilai

    2015-01-01

    Enhancing the production of aquatic animals is crucial for fishery management and aquaculture applications. Ovaries are specialized tissues that play critical roles in producing oocytes and hormones. Significant biochemical changes take place during the sexual maturation of Portunus trituberculatus, but the genetics of this process has not been extensively studied. Transcriptome sequencing can be used to determine gene expression changes within specific periods. In the current study, we used transcriptome sequencing to produce a comprehensive transcript dataset for the ovarian development of P. trituberculatus. Approximately 100 million sequencing reads were generated, and 126,075 transcripts were assembled. Functional annotation of the obtained transcripts revealed important pathways in ovarian development, such as those involving the vitellogenin gene. Also, we performed deep sequencing of ovaries in phases III and IV of sexual maturation in P. trituberculatus. Differential analysis of gene expression identified 506 significantly differentially expressed genes, which belong to 20 pathway, transporters, development, transcription factors, metabolism of other amino acids, carbohydrate and lipid, solute carrier family members, and enzymes. Taken together, our study provides the first comprehensive transcriptomic resource for P. trituberculatus ovaries, which will strengthen understanding of the molecular mechanisms underlying the sexual maturation process and advance molecular nutritional studies of P. trituberculatus. PMID:26431399

  5. High intensity focused ultrasound (HIFU) treatment of BPH: results of a multi-center phase III study

    NASA Astrophysics Data System (ADS)

    Sanghvi, N.; Gardner, T.; Koch, M.; Bihrle, R.; Foster, R.; Resnick, M.; Seftel, A.; Grunberger, I.; Stiedle, C.; Corchan, J.

    2003-04-01

    The five centers phase III trial was to show that HIFU can treat prostate tissue thermally for symptomatic relief of BPH and improve flow rates. At five sites, 68 BPH patients were treated with the Sonablate device (Focus Surgery, Inc. Indianapolis, IN). A urethral Foley catheter was inserted into the urethra to aid in positioning and was kept in-situ during the treatment. A cooling device was used to cool the rectal wall. The patients returned home within a few hours after the procedure. The Foley catheter was kept electively to avoid any incidence of acute urinary retention following the therapy. The catheter was removed after 4-5 days. The average treatment time was 38 minutes. The patients were treated without pain, blood loss or complications. At 90 days post treatment, average Qmax and AUA Symptom Scores improved from 8.7 ml/s to 12.66 ml/s (48%) and 23.06 to 11.62 (52%), respectively. Significant prostate tissue changes took place before and after the treatment. 80% of the patients had cavity formation at the site of treatment at the bladder neck and prostate. Nonsurgical HIFU therapy is safe and effective for providing symptomatic relief of BPH symptoms and the treatment can be performed as an outpatient procedure.

  6. Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma

    SciTech Connect

    Safran, Howard . E-mail: hsafran@lifespan.org; Di Petrillo, Thomas; Akerman, Paul; Ng, Thomas; Evans, Devon; Steinhoff, Margaret; Benton, David; Purviance, John; Goldstein, Lisa; Tantravahi, Umadevi; Kennedy, Teresa R.N.

    2007-02-01

    Purpose: To determine the overall survival for patients with locally advanced, HER2 overexpressing, esophageal adenocarcinoma receiving trastuzumab, paclitaxel, cisplatin, and radiation on a Phase I-II study. Methods and Materials: Patients with adenocarcinoma of the esophagus without distant organ metastases and 2+/3+ HER2 overexpression by immunohistochemistry (IHC) were eligible. All patients received cisplatin 25 mg/m{sup 2} and paclitaxel 50 mg/m{sup 2} weekly for 6 weeks with radiation therapy (RT) 50.4 Gy. Patients received trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg. Results: Nineteen patients were entered: 7 (37%) had celiac adenopathy, and 7 (37%) had retroperitoneal, portal adenopathy, or scalene adenopathy. Fourteen of 19 patients (74%) had either 3+ HER2 expression by immunohistochemistry, or an increase in HER2 gene copy number by HER2 gene amplification or high polysomy by fluorescence in situ hybridization. The median survival of all patients was 24 months and the 2-year survival was 50%. Conclusions: Assessment of the effect of trastuzumab in the treatment of patients with esophageal adenocarcinoma overexpressing HER2 is limited by the small number of patients in this study. Overall survival, however, was similar to prior studies without an increase in toxicity. Evaluation of HER2 status should be performed in future trials for patients with adenocarcinoma of the esophagus that investigate therapies targeting the HER family.

  7. Iodixanol vs iopamidol in intravenous DSA of the abdominal aorta and lower extremity arteries: a comparative phase-III trial.

    PubMed

    Fischbach, R; Landwehr, P; Lackner, K; Nossen, J O; Heindel, W; Berg, K J; Eichhorn, G; Jacobsen, T F

    1996-01-01

    Iodixanol (Visipaque, 320 mgI/ml) was compared with iopamidol (Solutrast, 370 mgI/ml) in a double-blind, randomized, parallel group, intravenous DSA phase-III trial for evaluation of safety and efficacy. A total of 117 patients received iodixanol (n = 60) or iopamidol (n = 57). Diagnostic efficacy was evaluated using categoric and visual analogue scales. Discomfort and adverse events were recorded. A total of 39 patients collected urine up to 72 h after the examination for analysis. Diagnostic efficacy and radiographic density were similar in both groups. Discomfort was milder with iodixanol. The difference between the frequency of adverse events between both groups (iodixanol = 7, iopamidol = 2) was without statistical significance. Creatinine clearance was slightly more affected by iodixanol, whereas the increase in renal excretion of N-acetyl-beta-glucosaminidase (NAG) in the first 24-h collection period after the examination was significantly higher (p < 0.01) with iopamidol. Iodixanol was of equal diagnostic efficacy compared with iopamidol despite its reduced iodine content. Both contrast media are well suited for IV DSA.

  8. Solid phase extraction of gold(III) on attapulgite modified with triocarbohydrazide prior to its determination in environmental samples by ICP-OES.

    PubMed

    Zhang, Li; Li, Zhenhua; Hu, Zheng; Chang, Xijun

    2011-09-01

    The first study on the high efficiency of triocarbohydrazide modified attapulgite as solid-phase extractant for preconcentration of trace Au(III) prior to the measurement by inductively coupled plasma optical emission spectrometry (ICP-OES) has been reported. Experimental conditions for effective adsorption of trace levels of Au(III) were optimized with respect to different experimental parameters using batch and column procedures in detail. At pH 3, Au(III) could be quantitatively adsorbed on the new sorbent, and the adsorbed Au(III) could be completely eluted from the sorbent surface by 2.0mL 1.0molL(-1) of HCl+2% CS(NH(2))(2) solution. An enrichment factor of 150 was accomplished. Moreover, common interfering ions did not interfere in both separation and determination. The maximum adsorption capacity of the sorbent for Au(III) was found to be 66.7mgg(-1). The detection limit (3σ) of this method was 0.32μgL(-1) and the relative standard deviation (RSD) was 3.3% (n=8). The method, with high selectivity, sensitivity and reproducibility, was validated using certified reference materials, and had been applied for the determination of trace Au(III) with satisfactory results.

  9. Phase I/II Trial Evaluating Carbon Ion Radiotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma

    PubMed Central

    Kong, Lin; Hu, Jiyi; Guan, Xiyin; Gao, Jing; Lu, Rong; Lu, Jiade J.

    2016-01-01

    Background: Radiation therapy is the mainstay strategy for the treatment of nasopharyngeal cancer (NPC). Intensity-modulated X-ray therapy (IMXT) alone is the current standard for stage I and II NPC. For stage III and IV A/B diseases, concurrent chemotherapy should be provided in addition to IMXT. However, optimal treatment for locally recurrent NPC after previous definitive dose of radiotherapy is lacking. Various techniques including brachytherapy, IMXT, stereotactic radiosurgery or radiotherapy (SRS or SBRT) have been used in the management of locally recurrent NPC. Due to the inherent limitation of these techniques, i.e., limited range of irradiation or over-irradiation to surrounding normal tissues, moderate efficacy has been observed at the cost of severe toxicities. Carbon ion radiotherapy (CIRT) offers potential physical and biological advantages over photon and proton radiotherapy. Due to the inverted dose profile of particle beams and their greater energy deposition within the Bragg peak, precise dose delivery to the target volume(s) without exposing the surrounding organs at risk to extra doses is possible. In addition, CIRT provides an increased relative biological effectiveness (RBE) as compared to photon and proton radiotherapy. Such advantages may translate to improved outcomes after irradiation in terms of disease control in radio-resistant and previously treated, recurrent malignancies. It is therefore reasonable to postulate that recurrent NPC after high-dose radiotherapy could be more resistant to re-irradiation using photons. Reports on the treatment of radio-resistant malignancies in the head and neck region such as melanoma, sarcoma, and adenoid cystic carcinoma (ACC) have demonstrated superior local control rates from CIRT as compared to photon irradiation. Thus patients with recurrent NPC are likely to benefit from the enhanced biological effectiveness of carbon ions. As effective retreatment strategy is lacking for locally recurrent NPC

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

    NASA Astrophysics Data System (ADS)

    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

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

    SciTech Connect

    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

  12. Large fraction radiotherapy plus misonidazole for treatment of advanced lung cancer: report of a phase I/II trial

    SciTech Connect

    Simpson, J.R.; Perez, C.A.; Phillips, T.L.; Concannon, J.P.; Carella, R.J.

    1982-02-01

    From August 1978 through December 1979, 51 patients with advanced non-oat cell carcinoma of the lung were enrolled in a Phase I/II trial sponsored by the Radiation Therapy Oncology Group (RTOG) employing misonidazole (a 2-nitroimidazole) as a hypoxic cell sensitizer and radiation. The purpose of this study was to test drug and radiation tolerance and to assess the short term efficacy of this unconventional treatment. Tumor doses of 600 rad were given twice weekly for three weeks for a total of 3600 rad, preceded four to six hours by misonidazole in a dose of 2 gm/m/sup 2/ or 1.75 gm/m/sup 2/, administered orally. Forty-nine patients were evaluable. Serious toxicity from this treatment was rare. Grade 2 or 3 peripheral neuro-toxicity occurred in eight of 24 patients (33%) with drug doses of 2 gm/m/sup 2/ and in four of 26 patients (15%) who received 1.75 gm/m/sup 2/. Grade 3 or 4 central nervous system toxicity occurred in two patients. Two patients developed serious late radiation complications: one patient had a transverse myelitis that appeared one year following delivery of 3600 rad to the spinal cord; a second patient developed a tracheoesophageal fistula and pericarditis eight months following treatment. Objective responses were reported in 67% of patients (complete in 18%); 70% of the patients died with a median survival time of nine months. Of 32 patients eligible for 12 month follow-up, 34% survived more than one year. Patterns of relapse after initial treatment and comparison with results from other RTOG trials using conventional fractionation are discussed.

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

    PubMed

    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. PMID:27580113

  14. NOVEL CONCEPTS RESEARCH IN GEOLOGIC STORAGE OF CO2 PHASE III THE OHIO RIVER VALLEY CO2 STORAGE PROJECT

    SciTech Connect

    Neeraj Gupta

    2005-05-26

    As part of the Department of Energy's (DOE) initiation on developing new technologies for storage of carbon dioxide in geologic reservoir, Battelle has been awarded a project to investigate the feasibility of CO{sub 2} sequestration in the deep saline reservoirs in the Ohio River Valley region. This project is the Phase III of Battelle's work under the Novel Concepts in Greenhouse Gas Management grant. The main objective of the project is to demonstrate that CO{sub 2} sequestration in deep formations is feasible from engineering and economic perspectives, as well as being an inherently safe practice and one that will be acceptable to the public. In addition, the project is designed to evaluate the geology of deep formations in the Ohio River Valley region in general and in the vicinity of AEP's Mountaineer Power Plant in particular, in order to determine their potential use for conducting a long-term test of CO{sub 2} disposal in deep saline formations and potentially in nearby deep coal seams. The current technical progress report summarizes activities completed for the January through March 2005 period of the project. As discussed in the report, the technical activities focused on development of injection well design, preparing a Class V Underground Injection Control permit, assessment of monitoring technologies, analysis of coal samples for testing the capture system by Mitsubishi Heavy Industry, and presentation of project progress at several venues. In addition, related work has progressed on a collaborative risk assessment project with Japan research institute CREIPI and technical application for the Midwest Regional Carbon Sequestration Partnership.

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

    SciTech Connect

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

    2009-04-01

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

  16. Effectiveness of Cellulose Sulfate Vaginal Gel for the Prevention of HIV Infection: Results of a Phase III Trial in Nigeria

    PubMed Central

    Halpern, Vera; Ogunsola, Folasade; Obunge, Orikomaba; Wang, Chin-Hua; Onyejepu, Nneka; Oduyebo, Oyinola; Taylor, Doug; McNeil, Linda; Mehta, Neha; Umo-Otong, John; Otusanya, Sakiru; Crucitti, Tania; Abdellati, Said

    2008-01-01

    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 PMID:19023429

  17. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer

    PubMed Central

    Liu, Mei-Ching; Lee, Soo Chin; Vanlemmens, Laurence; Ferrero, Jean-Marc; Tabei, Toshio; Pivot, Xavier; Iwata, Hiroji; Aogi, Kenjiro; Lugo-Quintana, Roberto; Harbeck, Nadia; Brickman, Marla J.; Zhang, Ke; Kern, Kenneth A.; Martin, Miguel

    2010-01-01

    This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m2 (1,000 mg/m2 in patients >65 years) BID on days 1–14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16–1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC. PMID:20339913

  18. Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

    PubMed Central

    Macciò, Antonio; Madeddu, Clelia; Serpe, Roberto; Massa, Elena; Dessì, Mariele; Panzone, Filomena; Contu, Paolo

    2010-01-01

    Purpose. A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia—lean body mass (LBM), resting energy expenditure (REE), and fatigue—and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. Patients and Methods. Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. Results. Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. Conclusion. The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents. PMID:20156909

  19. Difluprednate 0.05% Versus Prednisolone Acetate 1% for Endogenous Anterior Uveitis: A Phase III, Multicenter, Randomized Study

    PubMed Central

    Sheppard, John D.; Toyos, Melissa M.; Kempen, John H.; Kaur, Paramjit; Foster, C. Stephen

    2014-01-01

    Purpose. Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition. Methods. This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily, alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54) eight times daily. The 14-day treatment period was followed by a 14-day dose-tapering period and a 14-day observation period. The primary efficacy end point was change in anterior chamber cell grade (range, 0 for ≤1 cell to 4 for >50 cells) from baseline to day 14. Results. At day 14, the mean change in anterior chamber cell grade with difluprednate was noninferior to that with prednisolone acetate (−2.2 vs. −2.0, P = 0.16). The proportions of difluprednate-treated patients versus prednisolone acetate–treated patients demonstrating complete clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate–treated patients, P = 0.0013) but not at other time points. The mean IOP values in both groups remained less than 21 mm Hg throughout the study. Conclusions. Difluprednate 0.05% four times daily is well tolerated and is noninferior to prednisolone acetate 1% eight times daily for the treatment of endogenous AU. (ClinicalTrials.gov number, NCT01201798.) PMID:24677110

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

    PubMed Central

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

    2014-01-01

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

  1. Ren Shen Yangrong Tang for Fatigue in Cancer Survivors: A Phase I/II Open-Label Study

    PubMed Central

    Xu, Yichen; Chen, Yanzhi

    2015-01-01

    Abstract Objectives: This open-label, prospective, phase I/II trial was performed to establish the safety and efficacy of Traditional Chinese Medicine (TCM) herbal products for treating non–anemia-related fatigue in patients with cancer. Although this practice is widespread in China, it has not been confirmed in a prospective clinical study. Design: Thirty-three patients who had completed cancer treatment, had stable disease and no anemia, and reported moderate to severe fatigue (rated ≥4 on a 0–10 scale) were enrolled in a TCM outpatient clinic. Patients took Ren Shen Yangrong Tang (RSYRT) decoction, a soup containing 12 TCM herbs, twice a day for 6 weeks. RSYRT aims to correct qi deficiency. Fatigue was assessed before and after RSYRT therapy, which all patients completed. Results: No discomfort or toxicity was observed. Before the study, all patients had had fatigue for at least 4 months. Fatigue severity decreased significantly from before therapy to 6 weeks after therapy: from 7.06 to 3.30 on a 0–10 scale (p<0.001). Fatigue category (mild, moderate, severe) shifted significantly (p=0.024): Of 22 patients with severe fatigue (rated ≥7) before therapy, 11 had mild fatigue and 11 had moderate fatigue after TCM treatment. The time-to-fatigue-alleviation was 2–3 weeks. Conclusion: RSYRT therapy was safe and was associated with fatigue improvement in nonanemic cancer survivors, consistent with historical TCM clinical practice experience. Because of a possible placebo effect in this open-label study, decoction RSYRT warrants further study in randomized clinical trials to confirm its effectiveness for managing moderate to severe fatigue. PMID:25918996

  2. Phase III, randomized controlled trial to evaluate lot consistency of a trivalent subunit egg-based influenza vaccine in adults.

    PubMed

    Rivera, Luis; Mazara, Sonia; Vargas, Maria; Fragapane, Elena; Casula, Daniela; Groth, Nicola

    2012-07-27

    Vaccination is the most effective preventive strategy to control influenza. The demonstration of lot-to-lot consistency to confirm the reliability of the manufacturing process has become a mandatory step in vaccine development. This phase III, observer-blind, controlled trial assessed lot-to-lot consistency, immunogenicity, and safety of a subunit trivalent influenza vaccine (Agrippal®, Novartis Vaccines and Diagnostics) in healthy adults aged 18-49 years. The immunogenicity and safety profile of Agrippal was compared with a control vaccine (Fluvirin®, Novartis Vaccines and Diagnostics). A total of 1507 subjects were randomized 2:2:2:1 to receive one vaccination of one of the three lots of influenza vaccine or control vaccine. Antibody levels were measured by hemagglutination inhibition assay on days 1 and 22. Adverse reactions were solicited via diary cards for 7 days after vaccination, and unsolicited adverse events were collected throughout the study period. Equivalence of day 22 immune responses to the three lots was shown for each of the three strains. Robust immunogenic responses after one dose were observed for all vaccine groups, and both Center for Biologics Evaluation and Research criteria for licensure of influenza vaccines were met for all three virus strains. Both vaccines exhibited a robust safety profile and were well tolerated, with no differences in local and systemic solicited reactions or in unsolicited adverse events. The demonstration of consistency between manufacturing lots confirms for purposes of clinical development the reliability of the production process. The robust immunogenic responses and favorable safety profiles further support the use of trivalent subunit influenza vaccines Agrippal and Fluvirin for active immunization against influenza. PMID:22659448

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

    PubMed

    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. PMID:27418551

  4. Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomized phase III trial TARGIT A.

    PubMed

    Sperk, Elena; Welzel, Grit; Keller, Anke; Kraus-Tiefenbacher, Uta; Gerhardt, Axel; Sütterlin, Marc; Wenz, Frederik

    2012-08-01

    The randomized phase III trial TARGIT A showed non-inferiority regarding local control after intraoperative radiotherapy (IORT 20 Gy which was followed by whole breast radiotherapy (WBRT) in patients with risk factors only) in comparison to standard WBRT (50-56 Gy) after breast-conserving surgery in selected patients. This is the first analysis of long-term toxicities in the setting of TARGIT. Between 02/2002 and 12/2008, 305 patients were treated within TARGIT A (Arm A: n = 34 IORT, n = 20 IORT + WBRT for risk factors; Arm B WBRT: n = 55) or received IORT as a planned boost (control group: n = 196) at a single center. Toxicity was assessed according to the LENT SOMA scales. No significant differences were seen between Arm A and Arm B regarding fibrosis, breast edema, retraction, ulceration, lymphedema, hyperpigmentation, and pain. Arm A had significantly less telangiectases compared to Arm B (p = 0.049). In the subanalysis (Arm A IORT vs. Arm A IORT + WBRT vs. Arm B), fibrosis had a cumulative rate of 5.9 versus 37.5 versus 18.4 %, respectively (38.2 % IORT boost control group), at 3 years. No telangiectases were seen after IORT alone (0 % Arm A IORT vs. 17.5 % Arm A IORT + WBRT vs. 17.7 % Arm B). The hazard ratio of higher grade toxicity as first event was 0.46 (95 % CI, 0.26-0.83) for Arm A IORT as compared to Arm B (p = 0.010). No recurrences were seen after a median follow-up of 40 months (Arm A) and 42 months (Arm B). With its very low chronic skin toxicity rates and outstanding long-term results regarding toxicity and local control, IORT with 50 kV X-rays is a safe and effective method for treatment of selected breast cancer patients. PMID:22842984

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

    PubMed

    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.

  6. Kinetics and Mechanisms of Cr(VI) Formation via the Oxidation of Cr(III) Solid Phases by Chlorine in Drinking Water.

    PubMed

    Chebeir, Michelle; Liu, Haizhou

    2016-01-19

    Hexavalent chromium Cr(VI), typically existing as the oxyanion form of CrO4(2-), is being considered for more stringent drinking water standards by regulatory agencies. Cr(VI) can be inadvertently produced via the oxidation of trivalent chromium Cr(III) solids. This study investigated the kinetics and mechanisms of Cr(III) solids oxidation by chlorine in drinking water and associated Cr(VI) formation. Batch experiments were carried out with three Cr(III) solids of environmental relevance, i.e., chromium hydroxide Cr(OH)3(s), chromium oxide Cr2O3(s), and copper chromite Cu2Cr2O5(s). Impacts of water chemical parameters including pH (6.0-8.5) and bromide concentration (0-5 mg/L) were examined. Results showed that the rapid oxidation of Cr(III) solid phases by chlorine was accompanied by Cr(VI) formation and an unexpected production of dissolved oxygen. Analysis of reaction stoichiometry indicated the existence of Cr intermediate species that promoted the autocatalytic decay of chlorine. An increase in pH modestly enhanced Cr(VI) formation due to changes of reactive Cr(III) surface hydroxo species. Bromide, a trace chemical constituent in source waters, exhibited a catalytic effect on Cr(VI) formation due to an electron shuttle mechanism between Cr(III) and chlorine and the bypass of Cr intermediate formation. The kinetics data obtained from this study suggest that the oxidation of Cr(III) solids by chlorine in water distribution systems can contribute to Cr(VI) occurrence in tap water, especially in the presence of a trace level of bromide. PMID:26647114

  7. Kinetics and Mechanisms of Cr(VI) Formation via the Oxidation of Cr(III) Solid Phases by Chlorine in Drinking Water.

    PubMed

    Chebeir, Michelle; Liu, Haizhou

    2016-01-19

    Hexavalent chromium Cr(VI), typically existing as the oxyanion form of CrO4(2-), is being considered for more stringent drinking water standards by regulatory agencies. Cr(VI) can be inadvertently produced via the oxidation of trivalent chromium Cr(III) solids. This study investigated the kinetics and mechanisms of Cr(III) solids oxidation by chlorine in drinking water and associated Cr(VI) formation. Batch experiments were carried out with three Cr(III) solids of environmental relevance, i.e., chromium hydroxide Cr(OH)3(s), chromium oxide Cr2O3(s), and copper chromite Cu2Cr2O5(s). Impacts of water chemical parameters including pH (6.0-8.5) and bromide concentration (0-5 mg/L) were examined. Results showed that the rapid oxidation of Cr(III) solid phases by chlorine was accompanied by Cr(VI) formation and an unexpected production of dissolved oxygen. Analysis of reaction stoichiometry indicated the existence of Cr intermediate species that promoted the autocatalytic decay of chlorine. An increase in pH modestly enhanced Cr(VI) formation due to changes of reactive Cr(III) surface hydroxo species. Bromide, a trace chemical constituent in source waters, exhibited a catalytic effect on Cr(VI) formation due to an electron shuttle mechanism between Cr(III) and chlorine and the bypass of Cr intermediate formation. The kinetics data obtained from this study suggest that the oxidation of Cr(III) solids by chlorine in water distribution systems can contribute to Cr(VI) occurrence in tap water, especially in the presence of a trace level of bromide.

  8. Magnetic solid-phase extraction combined with graphite furnace atomic absorption spectrometry for speciation of Cr(III) and Cr(VI) in environmental waters.

    PubMed

    Jiang, Hong-mei; Yang, Ting; Wang, Yan-hong; Lian, Hong-zhen; Hu, Xin

    2013-11-15

    A new approach of magnetic solid phase extraction (MSPE) coupled with graphite furnace atomic absorption spectrometry (GFAAS) has been developed for the speciation of Cr(III) and Cr(VI) using zincon-immobilized silica-coated magnetic Fe3O4 nanoparticles (Zincon-Si-MNPs) as the MSPE absorbent. Cr(III) was quantitatively reserved on the absorbent at pH 9.1 while total Cr was reserved at pH 6.5. The absorbed Cr species were eluted by using 2 mol/L HCl and detected by GFAAS. The concentration of Cr(VI) could be calculated by subtracting Cr(III) from total Cr. All the parameters affecting the separation and extraction efficiency of Cr species such as pH, extraction time, concentration and volume of eluent, sample volume and influence of co-existing ions were systematically examined and the optimized conditions were established accordingly. The detection limit (LOD) of the method was 0.016 and 0.011 ng mL(-1) for Cr(III) and Cr(VI), respectively, with the enrichment factor of 100 and 150. The precisions of this method (Relative standard deviation, RSD, n=7) for Cr(III) and Cr(VI) at 0.1 ng mL(-1) were 6.0% and 6.2%, respectively. In order to validate the proposed method, a certified reference material of environmental water was analyzed, and the result of Cr speciation was in good agreement with the certified value. This MSPE-GFAAS method has been successfully applied for the speciation of Cr(III) and Cr(VI) in lake and tap waters with the recoveries of 88-109% for the spiked samples. Moreover, the MSPE separation mechanism of Cr(III) and Cr(VI) based on their adsorption-desorption on Zincon-Si-MNPs has been explained through various spectroscopic characterization.

  9. Integrated Fast Neutron Flux at the End of Phases I, II, III, and IV-1B of the MOX Zr-cladding Tube

    SciTech Connect

    Gray Chang

    2004-03-01

    This report using the detailed ATR quarter core model calculated neutronic tallies, the MCWO-calculated Zr-cladding fast neutron fluence (E > 0.1 MeV and E > 1.0 MeV) distributions at the end of Phase-I, -II, -III, and -IV Irradiation are tabulated in Table 1, 2, 3, and 4. At the end of the Phase-I irradiation, the MCWO-calculated Zr-cladding fast neutron fluences of the removed MOX capsules 1 and 8 are 2.68 and 2.68 x 1020 n/cm2, respectively. At the end of Phase-II Irradiation are tabulated in Table 2. At the end of the Phase-II irradiation, the MCWO-calculated Zr-cladding fast neutron fluences of the removed MOX capsules 9 and 2 are 6.78 and 6.79 x 1020 n/cm2, respectively. At the end of the Phase-III irradiation, the MCWO-calculated Zr-cladding fast neutron fluences of the removed MOX capsules 10 and 3 are 9.82 and 9.70 x 1020 n/cm2, respectively. And, at the end of the Phase-IV part 1B irradiation, the MCWO-calculated Zr-cladding fast neutron fluences of the removed MOX capsules 4 and 13 are 1.41 and 1.39 x 1021 n/cm2, respectively.

  10. 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.

    PubMed

    Zeng, Chujie; Lin, Yao; Zhou, Neng; Zheng, Jiaoting; Zhang, Wei

    2012-10-30

    A new method for the speciation of Cr(VI) and Cr(III) based on enhancement effect of room temperature ionic liquids (RTILs) for hollow fiber liquid phase microextraction (HF-LPME) combined with flame atomic absorption spectrometry (FAAS) was developed. Room temperature ionic liquids (RTILs) and diethyldithiocarbamate (DDTC) were used enhancement reagents and chelating reagent, respectively. The addition of room temperature ionic liquids led to 3.5 times improvement in the determination of Cr(VI). In this method, Cr(VI) reacts with DDTC yielding a hydrophobic complex, which is subsequently extracted into the lumen of hollow fiber, whereas Cr(III) is remained in aqueous solutions. The extraction organic phase was injected into FAAS for the determination of Cr(VI). Total Cr concentration was determined after oxidizing Cr(III) to Cr(VI) in the presence of KMnO(4) and using the extraction procedure mentioned above. Cr(III) was calculated by subtracting of Cr(VI) from the total Cr. Under optimized conditions, a detection limit of 0.7 ng mL(-1) and an enrichment factor of 175 were achieved. The relative standard deviation (RSD) was 4.9% for Cr(VI) (40 ng mL(-1), n=5). The proposed method was successfully applied to the speciation of chromium in natural water samples with satisfactory results. PMID:22981284

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

    PubMed

    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.

  12. Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results.

    PubMed

    Yang, Xiaohong; Lee, Sang-Rok; Choi, Yun-Seok; Alexander, Veronica J; Digenio, Andres; Yang, Qingqing; Miller, Yury I; Witztum, Joseph L; Tsimikas, Sotirios

    2016-04-01

    Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.0+ antisense drug that targets apoC3 mRNA in patients with hypertriglyceridemia, including familial chylomicronemia syndrome (n = 3), volanesorsen monotherapy (n = 51), and as add-on to fibrate (n = 26), treated for 85 days and followed for 176 days. Compared with placebo, volanesorsen was associated with an 82.3 ± 11.7%, 81.3 ± 15.7%, and 80.8 ± 13.6% reduction in apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoA-I, respectively (300 mg dose;P< 0.001 for all), at day 92. Strong correlations in all assay measures were noted with total plasma apoC-III, chylomicron-apoC-III, and VLDL-apoC-III. In conclusion, novel high-throughput ELISAs were developed to detect lipoprotein-associated apoC-III, including for the first time on Lp(a). Volanesorsen uniformly lowers apoC-III on apoB-100, Lp(a), and apoA-I lipoproteins, and may be a potent agent to reduce triglycerides and cardiovascular risk mediated by apoC-III.

  13. Spotlight: Costa Rica.

    PubMed

    1998-03-01

    3.5 million people lived in Costa Rica as of mid-1997. There were 24 births and 4 deaths per 1000 population, respectively, contributing to the annual natural increase rate of 2.0%. Each woman in Costa Rica bears an average of 2.8 children during her reproductive lifespan and men and women were expected to live for 73 and 78 years, respectively. Costa Rica's low infant mortality rate and high literacy and life expectancy rates set it apart from the rest of Central America. Costa Rica is also the only country in the region which maintains no standing army. About 96% of the population is White or Mestizo, 3% is Black, and 1% is indigenous Indian. More than half of the country lives in San Jose and its metropolitan area, 6% of the country's total land area. Unemployment has run near 5% over the past 2 years, but much of the labor force is underemployed. Costa Rica's economy depends upon tourism and agricultural exports such as coffee, beef, and bananas. A large Intel factory opened in 1997. The government and Costa Rican environmentalists are planning a joint campaign to reconvert 80% of Costa Rica's pasture back to forest and tree crops. About 20% of the government's budget is spent upon education and the 93% literacy rate is the highest in the region. Government health services provide low-cost contraceptives to more than 75% of users and 75% of women use some form of family planning. PMID:12321532

  14. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial

    PubMed Central

    Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John MS; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

    2009-01-01

    Summary Background Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. Methods In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2 at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m2 at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m2 at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. Findings All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0·95, 95% CI 0·85–1·08; p=0·44). 75·6% (95% CI 73·7–77·5) of patients in the experimental group and 74·3% (72·3–76·2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0·0001); the most frequent events were neutropenia (937 events vs 797 events

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

    PubMed

    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 < 0.001) and Clinical Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P < 0.001). Common treatment-emergent adverse events (≥5% and twice the rate of placebo) in both cariprazine groups were akathisia, extrapyramidal disorder, and tremor; most were mild to moderate in severity. Mean changes in metabolic parameters were generally small and similar between groups. Prolactin levels decreased in all groups. In conclusion, cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters. Cariprazine was generally well tolerated. These results suggest that cariprazine may be a new and effective treatment for schizophrenia. PMID:26075487

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

    PubMed Central

    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. PMID:27752357

  17. Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial

    PubMed Central

    Shaw, E; Miró, J M; Puig-Asensio, M; Pigrau, C; Barcenilla, F; Murillas, J; Garcia-Pardo, G; Espejo, E; Padilla, B; Garcia-Reyne, A; Pasquau, J; Rodriguez-Baño, J; López-Contreras, J; Montero, M; de la Calle, C; Pintado, V; Calbo, E; Gasch, O; Montejo, M; Salavert, M; Garcia-Pais, M J; Carratalà, J; Pujol, M

    2015-01-01

    Introduction Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. Methods and analysis A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. Ethics and dissemination The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals

  18. Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study

    PubMed Central

    Nilsson, S.; Cislo, P.; Sartor, O.; Vogelzang, N. J.; Coleman, R. E.; O'Sullivan, J. M.; Reuning-Scherer, J.; Shan, M.; Zhan, L.; Parker, C.

    2016-01-01

    Background Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P). Patients and methods Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study. Results Analyses were carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo {29.2% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 [95% confidence interval (CI) 1.21–2.74]}. Findings were similar for FACT-P total score [24.6% versus 16.1%, respectively; P = 0.020; OR = 1.70 (95% CI 1.08–2.65)]. A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95

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

    PubMed

    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. Taking Personalized Medicine Seriously: Biomarker Approaches in Phase IIb/III Studies in Major Depression and Schizophrenia

    PubMed Central

    Laughren, Thomas; Lamers, Femke; Picard, Rosalind; Walther, Sebastian; Goff, Donald; Sainati, Stephen

    2015-01-01

    and integration of such markers into clinical research is both required and feasible in order to meet the benefit of personalized medicine. This article is based on proceedings from the “Taking Personalized Medicine Seriously—Biomarker Approaches in Phase IIb/III Studies in Major Depression and Schizophrenia” session, which was held during the 10th Annual Scientific Meeting of the International Society for Clinical Trials Meeting (ISCTM) in Washington, DC, February 18 to 20, 2014. PMID:25977838

  1. Efficacy of the HPV-16/18 Vaccine: Final according to protocol results from the blinded phase of the randomized Costa Rica HPV-16/18 Vaccine Trial

    PubMed Central

    Hildesheim, Allan; Wacholder, Sholom; Catteau, Gregory; Struyf, Frank; Dubin, Gary; Herrero, Rolando

    2014-01-01

    Background A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine (NCT00128661). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated. Methods We randomized (3,727 HPV arm; 3,739 Control arm), vaccinated (HPV-16/18 or Hepatitis A) and followed (median 53.8 months) 7,466 healthy women aged 18-25 years. 5,312 women (2,635 HPV arm; 2,677 Control arm) were included in the according to protocol analysis for efficacy. The full cohort was evaluated for safety. Immunogenicity was considered on a subset of 354 (HPV-16) and 379 (HPV-18) women. HPV type was assessed by PCR on cytology specimens. Immunogenicity was assessed using ELISA and inhibition enzyme immunoassays. Disease outcomes were histologically confirmed. Vaccine efficacy and 95% confidence intervals (95%CI) were computed. Results Vaccine efficacy was 89.8% (95% CI: 39.5 - 99.5; N=11 events total) against HPV-16/18 associated CIN2+, 59.9% (95% CI: 20.7 - 80.8; N=39 events total) against CIN2+ associated with non-HPV-16/18 oncogenic HPVs and 61.4% (95% CI: 29.5-79.8; N=51 events total) against CIN2+ irrespective of HPV type. The vaccine had an acceptable safety profile and induced robust and long-lasting antibody responses. Conclusions Our findings confirm the high efficacy and immunogenicity of the HPV-16/18 vaccine against incident HPV infections and cervical disease associated with HPV-16/18 and other oncogenic HPV types. These results will serve as a benchmark to which we can compare future findings from ongoing extended

  2. Effect of Protein Incorporation on the Nanostructure of the Bicontinuous Microemulsion Phase of Winsor-III Systems: A Small-Angle Neutron Scattering Study

    SciTech Connect

    Hayes, Douglas G.; Gomez del Rio, Javier A.; Ye, Ran; Urban, Volker S.; Pingali, Sai Venkatesh; O’Neill, Hugh M.

    2015-01-20

    Small-angle neutron scattering (SANS) analysis using the Teubner₋Strey model has been employed to evaluate the effect of protein incorporation into the middle, bicontinuous microemulsion (BμE) phase of Winsor-III (WIII) systems formed by an aerosol-OT (AOT)/alkyl ethoxylate mixed surfactant system to understand better the extraction of proteins into and out of BμEs and to study the effect of proteins on a system that serves as a biomimetic analog of cell membranes. Under conditions of high salinity, the incorporation of positively charged proteins cytochrome c, lysozyme, and α-chymotrypsin, near their solubilization limit in the BμEs promoted the release of water and oil from the BμEs, a decrease in the quasi-periodic repeat distance (d), an increase in ordering (a decrease in the amphiphilicity factor, fa) for the surfactant monolayers, and a decrease in the surface area per surfactant headgroup, suggesting that the proteins affected the self-assembly of components in the BμE phase and produced Debye shielding of AOTs sulfonate headgroup. For WIII systems possessing lower salinity, cytochrome c reduced the efficiency of surfactant in the BμE phase, noted by increases in d and fa, suggesting that the enzyme and AOT underwent ion pairing. We find that the results of this study demonstrate the importance of ionic strength to modulate proteinsurfactant interactions, which in turn will control the release of proteins encapsulated in the BμEs, relevant to WIII-based protein extraction and controlled release from BμE delivery systems, and demonstrate the utility of BμEs as a model system to understand the effect of proteins on biomembranes.

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

    SciTech Connect

    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.

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

    PubMed

    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. PMID:17455340

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

    PubMed

    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.

  6. Improving access to preparatory information for children undergoing general anaesthesia for tooth extraction and their families: study protocol for a Phase III randomized controlled trial

    PubMed Central

    2014-01-01

    Background Children can find anaesthesia induction especially distressing and postoperative psychological and physical morbidity are common. Preparation programmes for general anaesthesia (GA) are highly effective in reducing this distress. A Phase II study has already verified the effectiveness of a prototype preoperative GA-coping computer game to help children cope with induction in a dental GA setting. The biggest patient users of pediatric GA services in the UK are children who need to have teeth removed (estimated to be 100,000 yearly). Tooth decay is the most common disease in children worldwide. This study is a Phase III randomized controlled trial (RCT) and will evaluate the effectiveness of the new internet version of this game. Methods/design The Phase III RCT will use a double-blind three-armed design. The clinical trial will recruit up to 210 children and will compare the web-based game against standard care and another non-medical game. At least 53 patients in each group will be required for 90% statistical power. Distress will be assessed through an evaluation of the child’s behaviour during the visit and later parental reports of physical and psychological morbidity. The satisfaction of parents and children will be measured; the mode of usage of the web-based game will be automatically recorded and the impact on the service (for example, recovery time and throughput) will be reported. The Phase III study primary outcome will measure: (1) patient experience: acceptance of anaesthetic induction, child cooperation and distress, reduction of peri- and postoperative morbidity, child and family satisfaction, and (2) service improvement: anaesthetic time and improvement in throughput. Measures will be administered at baseline, at the time of the GA treatment visit, and at 48 hours and one week postoperatively. Discussion This study aims to determine the effectiveness of an online GA-coping game for children and families undergoing tooth extraction under

  7. Interfacial Area and Interfacial Transfer in Two-Phase Flow Systems (Volume III. Chapters 11-14)

    SciTech Connect

    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.

  8. A randomized Phase III trial of thoracoscopic versus open esophagectomy for thoracic esophageal cancer: Japan Clinical Oncology Group Study JCOG1409.

    PubMed

    Kataoka, Kozo; Takeuchi, Hiroya; Mizusawa, Junki; Ando, Masahiko; Tsubosa, Yasuhiro; Koyanagi, Kazuo; Daiko, Hiroyuki; Matsuda, Satoru; Nakamura, Kenichi; Kato, Ken; Kitagawa, Yuko

    2016-02-01

    A randomized Phase III study was commenced in May 2015 to confirm the non-inferiority of thoracoscopic esophagectomy to open esophagectomy in terms of overall survival for clinical Stage I-III esophageal cancer. A total of 300 patients will be accrued from Japanese institutions over 6 years. The primary endpoint is overall survival. The secondary endpoints are relapse-free survival, proportion of patients with R0 resection, proportion of patients who underwent re-operation, adverse events, postoperative respiratory function change, postoperative quality-of-life score (EORTC QLQ-C30), and proportion of patients who need conversion from thoracoscopic surgery to open surgery. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000017628.

  9. Water-soluble oxoglaucine-Y(III), Dy(III) complexes: in vitro and in vivo anticancer activities by triggering DNA damage, leading to S phase arrest and apoptosis.

    PubMed

    Wei, Jian-Hua; Chen, Zhen-Feng; Qin, Jiao-Lan; Liu, Yan-Cheng; Li, Zhu-Quan; Khan, Taj-Malook; Wang, Meng; Jiang, Yan-Hua; Shen, Wen-Ying; Liang, Hong

    2015-07-01

    Complexes of yttrium(III) and dysprosium(III) with the traditional Chinese medicine active ingredient oxoglaucine (OG), namely [Y(OG)2(NO3)3]·CH3OH (1) and [Dy(OG)2(NO3)3]·H2O (2), were synthesized and characterized by elemental analysis, IR, ESI-MS, (1)H and (13)C NMR as well as single-crystal X-ray diffraction analysis. In vitro the complexes exhibited higher anticancer activity than the free ligand OG against the tested cancer cell lines. Among the tested cell lines, HepG2 is the most sensitive to the complexes. Complex 2 can trigger DNA damage in HepG2 cells, resulting in cell cycle arrest in the S phase and leading to cell apoptosis. The S phase cell-cycle arrest is caused via the ATM (ataxia-telangiectasia mutated)-Chk2-Cdc25A pathway. Chk2 is phosphorylated and activated in an ATM-dependent manner. It, in turn, phosphorylates Cdc25A phosphatise on serine124, causing the inactivation of Cdc25A in ubiquitin-mediated proteolytic degradation. The cyclin-Cdk complexes of the S phase could also be inhibited by limited supply of cyclins A and E. This irreversible cell cycle arrest process ultimately induces mitochondria-involved apoptotic cell death via the activation of Bcl-2 protein. Complex e2 ffectively inhibited tumour growth in the BEL-7402 xenograft mouse model and exhibited higher safety in vivo than cisplatin. PMID:26017376

  10. Water-soluble oxoglaucine-Y(III), Dy(III) complexes: in vitro and in vivo anticancer activities by triggering DNA damage, leading to S phase arrest and apoptosis.

    PubMed

    Wei, Jian-Hua; Chen, Zhen-Feng; Qin, Jiao-Lan; Liu, Yan-Cheng; Li, Zhu-Quan; Khan, Taj-Malook; Wang, Meng; Jiang, Yan-Hua; Shen, Wen-Ying; Liang, Hong

    2015-07-01

    Complexes of yttrium(III) and dysprosium(III) with the traditional Chinese medicine active ingredient oxoglaucine (OG), namely [Y(OG)2(NO3)3]·CH3OH (1) and [Dy(OG)2(NO3)3]·H2O (2), were synthesized and characterized by elemental analysis, IR, ESI-MS, (1)H and (13)C NMR as well as single-crystal X-ray diffraction analysis. In vitro the complexes exhibited higher anticancer activity than the free ligand OG against the tested cancer cell lines. Among the tested cell lines, HepG2 is the most sensitive to the complexes. Complex 2 can trigger DNA damage in HepG2 cells, resulting in cell cycle arrest in the S phase and leading to cell apoptosis. The S phase cell-cycle arrest is caused via the ATM (ataxia-telangiectasia mutated)-Chk2-Cdc25A pathway. Chk2 is phosphorylated and activated in an ATM-dependent manner. It, in turn, phosphorylates Cdc25A phosphatise on serine124, causing the inactivation of Cdc25A in ubiquitin-mediated proteolytic degradation. The cyclin-Cdk complexes of the S phase could also be inhibited by limited supply of cyclins A and E. This irreversible cell cycle arrest process ultimately induces mitochondria-involved apoptotic cell death via the activation of Bcl-2 protein. Complex e2 ffectively inhibited tumour growth in the BEL-7402 xenograft mouse model and exhibited higher safety in vivo than cisplatin.

  11. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02

    PubMed Central

    Wen, Patrick Y.; Chang, Susan M.; Lamborn, Kathleen R.; Kuhn, John G.; Norden, Andrew D.; Cloughesy, Timothy F.; Robins, H. Ian; Lieberman, Frank S.; Gilbert, Mark R.; Mehta, Minesh P.; Drappatz, Jan; Groves, Morris D.; Santagata, Sandro; Ligon, Azra H.; Yung, W.K. Alfred; Wright, John J.; Dancey, Janet; Aldape, Kenneth D.; Prados, Michael D.; Ligon, Keith L.

    2014-01-01

    Background Inhibition of epidermal growth factor receptor (EGFR) and the mechanistic target of rapamycin (mTOR) may have synergistic antitumor effects in high-grade glioma patients. Methods We conducted a phase I/II study of the EGFR inhibitor erlotinib (150 mg/day) and the mTOR inhibitor temsirolimus. Patients initially received temsirolimus 50 mg weekly, and the dose adjusted based on toxicities. In the phase II component, the primary endpoint was 6-month progression-free survival (PFS6) among glioblastoma patients. Results Twenty-two patients enrolled in phase I, 47 in phase II. Twelve phase I patients treated at the maximum tolerated dosage were included in the phase II cohort for analysis. The maximum tolerated dosage was 15 mg temsirolimus weekly with erlotinib 150 mg daily. Dose-limiting toxicities were rash and mucositis. Among 42 evaluable glioblastoma patients, 12 (29%) achieved stable disease, but there were no responses, and PFS6 was 13%. Among 16 anaplastic glioma patients, 1 (6%) achieved complete response, 1 (6%) partial response, and 2 (12.5%) stable disease, with PFS6 of 8%. Tumor levels of both drugs were low, and posttreatment tissue in 3 patients showed no reduction in the mTOR target phosphorylated (phospho-)S6S235/236 but possible compensatory increase in phospho-AktS473. Presence of EGFR variant III, phospho-EGFR, and EGFR amplification did not correlate with survival, but patients with elevated phospho–extracellular signal-regulated kinase or reduced phosphatase and tensin homolog protein expression had decreased progression-free survival at 4 months. Conclusion Because of increased toxicity, the maximum tolerated dosage of temsirolimus in combination with erlotinib proved lower than expected. Insufficient tumor drug levels and redundant signaling pathways may partly explain the minimal antitumor activity noted. PMID:24470557

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

    PubMed Central

    Riley, John H; Tabberer, Maggie; Richard, Nathalie; Donald, Alison; Church, Alison; Harris, Stephanie S

    2016-01-01

    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 Handi-Haler® 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 in the Phase IIIb active comparator study. Conclusion Delivery of UMEC/VI via the Ellipta™ DPI was considered easy-to-use, and patients with COPD demonstrated clear preference for this inhaler compared with HandiHaler®. PMID:27578968

  13. Adsorption of As(III), As(V) and Cu(II) on zirconium oxide immobilized alginate beads in aqueous phase.

    PubMed

    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.

  14. Adsorption of As(III), As(V) and Cu(II) on zirconium oxide immobilized alginate beads in aqueous phase.

    PubMed

    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. PMID:27372261

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

    PubMed Central

    2011-01-01

    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 < 90% at baseline. This favorable effect was accompanied by categorical change in VC and progression-free survival time. In the subpopulation, pirfenidone significantly suppressed cough and dyspnea. Conclusions IPF patients having %VC ≥ 70% and SpO2 < 90% at baseline will most likely benefit from pirfenidone when evaluated using changes in VC (and %VC), and cough and dyspnea symptoms. This subpopulation could expect to benefit most from pirfenidone treatment. Trial Registration This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (Registration Number: JAPICCTI-050121). PMID:22035508

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

    NASA Technical Reports Server (NTRS)

    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.

  17. 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).

    PubMed

    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.

  18. Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Herchenhorn, Daniel; Dias, Fernando L.; Viegas, Celia M.P.; Federico, Miriam H.; Araujo, Carlos Manoel M.; Small, Isabelle; Bezerra, Marcos; Fontao, Karina M.D.; Knust, Renata E.; Ferreira, Carlos G.; Martins, Renato G.

    2010-11-01

    Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.

  19. DEMONSTRATION OF FUEL CELLS TO RECOVER ENERGY FROM LANDFILL GAS - PHASE III. DEMONSTRATION TESTS - PHASE IV. GUIDELINES AND DEMONSTRATIONS - VOLUME 2. APPENDICES

    EPA Science Inventory

    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...

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

    EPA Science Inventory

    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...

  1. Use of vancomycin silica stationary phase in packed capillary electrochromatography: III. enantiomeric separation of basic compounds with the polar organic mobile phase.

    PubMed

    Fanali, Salvatore; Catarcini, Paolo; Quaglia, Maria Giovanna

    2002-02-01

    The separation of basic compounds into their enantiomers was achieved using capillary electrochromatography in 50 or 75 microm inner diameter (ID) fused-silica capillaries packed with silica a stationary phase derivatized with vancomycin and mobile phases composed of mixtures of polar organic solvents containing 13 mM ammonium acetate. Enantiomer resolution, electroosmotic flow, and the number of theoretical plates were strongly influenced by the type and concentration of the organic solvent. Mobile phases composed of 13 mM ammonium acetate dissolved in mixtures of acetonitrile/methanol, ethanol, n-propanol, or isopropanol were tested and the highest enantioresolutions were achieved using the first mobile phase, allowing the separation of almost all investigated enantiomers (9 from 11 basic compounds). The use of capillaries with different ID (50 and 75 microm ID) packed with the same chiral stationary phase revealed that a higher number of theoretical plates and higher enantioresolution was achieved with the tube with lowest ID.

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

    PubMed Central

    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.

    2012-01-01

    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. PMID:23099651

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

    PubMed

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

    2016-02-01

    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

  6. Determination of rhodium by resonance light-scattering technique coupled with solid phase extraction using Rh(III) ion-imprinted polymers as sorbent.

    PubMed

    Yang, Bing; Zhang, Ting; Tan, Wenxiang; Liu, Peng; Ding, Zhongtao; Cao, Qiue

    2013-02-15

    A resonance light-scattering method (RLS) for the determination of Rh(III) was initially developed, based on the reaction among Rh(III), WO4(2-) and ethylrhodamine B. The method possesses high sensitivity, but lacks selectivity. Therefore, a Rh(III) ion-imprinted polymer (IIP), prepared by precipitation polymerization using 2-(allylthio)nicotinic acid (ANA) as functional monomer, was used as sorbent to construct a ion-imprint based solid-phase extraction (IIP-SPE) method for separation of rhodium from complicated matrices prior to its determination by RLS. The experimental parameters affecting the extraction efficiency and selectivity of IIP-SPE were studied carefully. Under the optimal conditions, the IIP-SPE column with the enrichment factor (EF) of 10 could be used at least 20 times without decreasing its extraction recovery (above 90%) significantly. The calibration graph for the determination of rhodium by RLS coupled with IIP-SPE procedure was linear in the range of 0.06-1.5 ng mL(-1) with the detection limit of 0.024 ng mL(-1). There is no metal ions tested at the concentration below 10 ng mL(-1) interfered in the determination of 0.8 ng mL(-1) Rh(III). The proposed IIP-SPE-RLS method was successfully applied to the extraction and measurement of trace rhodium in catalyst, water and geochemical samples with the relative standard deviation (RSD) of less than 4.0% (n=4).

  7. Phase II Study of Chemoradiotherapy With 5-Fluorouracil and Cisplatin for Stage II-III Esophageal Squamous Cell Carcinoma: JCOG Trial (JCOG 9906)

    SciTech Connect

    Kato, Ken; Muro, Kei; Minashi, Keiko; Ohtsu, Atsushi; Ishikura, Satoshi; Boku, Narikazu; Takiuchi, Hiroya; Komatsu, Yoshito; Miyata, Yoshinori; Fukuda, Haruhiko

    2011-11-01

    Purpose: In this Phase II study, we evaluated the efficacy and toxicity of chemoradiotherapy (CRT) with cisplatin (CDDP) and 5-fluorouracil (5-FU) for Stage II-III esophageal squamous cell carcinoma (ESCC). Patients and Methods: Patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) thoracic ESCC were enrolled between April 2000 and March 2002. Chemotherapy comprised two courses of protracted infusion of 5-FU (400 mg/m{sup 2}/day) on Days 1-5 and 8-12, and 2-h infusion of CDDP (40 mg/m{sup 2}) on Days 1 and 8; this regimen was repeated every 5 weeks. Concurrent radiotherapy involved 60-Gy irradiation (30 fractions) for 8 weeks with a 2-week break. Responders received two courses of 5-FU (800 mg/m{sup 2}/day) on Days 1-5 and CDDP (80 mg/m{sup 2}) on Day 1. Final analysis was conducted in March 2007. Survival and late toxicities were monitored for 5 years. Results: The characteristics of the 76 patients enrolled were as follows: median age, 61 years; male/female, 68/8; performance status 0/1, 59/17 patients; Stage IIA/IIB/III, 26/12/38 patients. Of the 74 eligible patients, 46 (62.2%) achieved complete response. Median survival time was 29 months, with 3- and 5-year survival rates of 44.7% and 36.8%, respectively. Acute toxicities included Grade 3/4 esophagitis (17%), nausea (17%), hyponatremia (16%), and infection without neutropenia (12%). Late toxicities comprised Grade 3/4 esophagitis (13%), pericardial (16%) and pleural (9%) effusion, and radiation pneumonitis (4%), causing 4 deaths. Conclusions: CRT is effective for Stage II-III ESCC with manageable acute toxicities and can provide a nonsurgical treatment option. However, further improvement is required for reduction in late toxicity.

  8. Simultaneous determination of Cr(iii) and Cr(vi) using reversed-phased ion-pairing liquid chromatography with dynamic reaction cell inductively coupled plasma mass spectrometry

    USGS Publications Warehouse

    Wolf, R.E.; Morrison, J.M.; Goldhaber, M.B.

    2007-01-01

    A method for the simultaneous determination of Cr(iii) and Cr(vi) species in waters, soil leachates and synthetic bio-fluids is described. The method uses reversed-phase ion-pairing liquid chromatography to separate the chromium species and a dynamic reaction cell (DRC??) equipped ICP-MS for detection of chromium. Separation of the chromium species is carried out in less than 2 min. Cr(iii) is complexed with ethylenediaminetetraacetic acid (EDTA) prior to separation by mixing samples with the mobile phase containing 2.0 mM tetrabutylammonium hydroxide (TBAOH), 0.5 mM EDTA (dipotassium salt), and 5% (vol/vol) methanol, adjusted to pH 7.6. The interfering 40Ar 12C+ background peak at mass 52 was reduced by over four orders of magnitude to less than 200 cps by using 0.65 mL min-1 ammonia as a reaction gas and an RPq setting on the DRC of 0.75. Method detection limits (MDLs) of 0.09 ??g L-1 for Cr(iii) and 0.06 ??g L-1 for Cr(vi) were obtained based on peak areas at mass 52 for 50 ??L injections of low level spikes. Reproducibility at 2 ??g L-1 was 3% RSD for 5 replicate injections. The tolerance of the method to various levels of common cations and anions found in natural waters and to matrix constituents found in soil leachates and simulated gastric and lung fluids was tested by performing spike recovery calculations for a variety of samples. ?? The Royal Society of Chemistry.

  9. Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: results from phase I/II studies, prospective randomized trials and future directions

    PubMed Central

    Tyndall, A; Saccardi, R

    2005-01-01

    Around 700 patients have received an autologous haematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease (AD). The majority of these have been within the context of phase I/II clinical trials and following international guidelines proposed 7 years ago. In general, a positive benefit/risk ratio has led to phase III prospective randomized controlled trials in multiple sclerosis (MS), systemic sclerosis (SSc) and rheumatoid arthritis (RA) in Europe. In the US, similar trials are being planned for SSc, MS and systemic lupus erythematosus (SLE). Transplant related mortality (TRM) has fallen in all disease subgroups since the inception due to more appropriate patient selection, and so far a clear advantage of the more intense myeloablative regimens in terms of remission induction and relapse rate has not emerged. Although each AD has a different profile, over a third of patients have sustained a durable remission, often with no further need for immunosuppressive drugs. In those who relapsed, many responded to agents which pre transplant had been ineffective. The study of immune reconstitution and gene expression pre and post HSCT is being undertaken to further understand the mechanism of autoimmunity. PMID:15958063

  10. Solid-phase extraction of gallium(III) with hydrophobic 8-quinolinol derivatives-impregnated resin from aqueous acidic and alkaline solutions.

    PubMed

    Hatori, Nahoko; Imura, Hisanori; Ohashi, Akira; Ohashi, Kousaburo

    2008-12-01

    Solid-phase extraction (SPE) of gallium(III) with hydrophobic 8-quinolinol derivatives (HQs)-impregnated resin from aqueous acidic and alkaline solutions has been investigated. The HQs used were 7-(4-ethyl-1-methyloctyl)-8-quinolinol (HEMOQ), 5-octyloxymethyl-8-quinolinol (HO(8)Q), 2-methyl-5-octyloxymethyl-8-quinolinol (HMO(8)Q), 5-dioctylaminomethyl-8-quinolinol (HN(8)Q), 7-bromo-5-octyloxymethyl-8-quinolinol (HBrO(8)Q), and 5-(2-ethylhexyloxymethyl)-8-quinolinol (HOEHQ). Various factors affecting the SPE, such as the substituents of the HQs, HCl and NaOH concentrations in the aqueous phase, the HQ concentration in the resin, and the equilibration time were clarified. The extractability for gallium(III) from the aqueous solution became higher in the following order: HBrO(8)Q < HEMOQ < HO(8)Q < HN(8)Q < HMO(8)Q at 3 mol l(-1) HCl; HMO(8)Q < HO(8)Q < HOEHQ < HEMOQ < HN(8)Q < HBrO(8)Q at pH 0.4; HMO(8)Q < HO(8)Q asymptotically equal to HOEHQ < HN(8)Q < HEMOQ at 3 mol l(-1) NaOH.

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

    PubMed

    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. PMID:22442004

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

    PubMed

    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.

  13. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial12

    PubMed Central

    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.

    2016-01-01

    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. PMID:27084426

  14. A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer

    PubMed Central

    Khurshid, Humera; Dipetrillo, Thomas; Ng, Thomas; Mantripragada, Kalyan; Birnbaum, Ariel; Berz, David; Radie-Keane, Kathy; Perez, Kimberly; Constantinou, Maria; Luppe, Denise; Schumacher, Andrew; Leonard, Kara; Safran, Howard

    2012-01-01

    Objectives: Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC. Methods: Patients with stage III locally advanced NSCLC received paclitaxel, 50 mg/m2/week, with carboplatin area under the curve (AUC) = 2, weekly for 7 weeks, and concurrent radiotherapy, 64.8 Gy. Three dose levels of dasatinib 50, 70, and 100 mg/day were planned. Results: 11 patients with locally advanced NSCLC were entered. At the 70 mg dose level 1 patient had grade 5 pneumonitis not responsive to therapy, and one patient had reversible grade 3 pneumonitis and grade 3 pericardial effusion. Due to these toxicities the Brown University Oncology Group Data Safety Monitoring Board terminated the study. Conclusion: Dasatinib could not be safely combined with concurrent chemoradiation for stage 3 lung cancer due to pneumonitis. PMID:22666662

  15. Costa Rica. Spotlight.

    PubMed

    Haub, C; Adams, J

    1985-05-01

    Costa Rica's demographic and economic characteristics are highlighted. Costa Rica's demographic situation is unique in certain respects. Between the late 1950s and the late 1970s, the total fertility rate declined from about 7 to 4 and then stabilized instead of continuing to decline to 2 as expected. This is especially surprising since the level of contraceptive use is similar to that of most European countries. Approximately 2/3 of all couples practice contraception. It is possible that the rate will slowly decline to the expected level, but a delayed decline will ultimately produce a much larger population than initially expected. The demographic situation in Costa Rica is being carefully monitored for insights which might be useful in predicting future fertility patterns in other developing countries. The government of Costa Rica recognizes that family planning is a necessary component of maternal and child health care; however, most family planning services are provided by private organizations. In 1982, population size was 2.6 million, the crude birth rate was 30.7, the crude death rate was 3.9, infant mortality was 19.3, and the rate of natural increase was 2.7%. The population is predominantly Spanish, and the indigenous population totals only 20,000. 48% of the population is urban. Costa Rica has a relatively stable deomocratic government. It relationshiops with other countries are generally peaceful, but tensions between Nicaragua and Costa Rica are increasing. The country's economic situation deteriorated in recent years due primarily to a decline in the price of coffee, the country's principle export commodity. The trade deficit increased markedly, unemployment increased, and income fell sharply. The economic slowdown is now showing signs of a reversal. In 1983 exports, consisting primarily of coffee, bananas, beef, sugar, cane and cacao, totalled US$871 million, and imports, consisting mainly of manufactured goods and equipment, chemicals, fuel, food

  16. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix.

    PubMed

    Maruyama, Y; VanNagell, J R; Yoneda, J; Donaldson, E; Gallion, H; Rowley, K; Kryscio, R; Beach, J L

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  17. 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).

    SciTech Connect

    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-Tropsch IV

  18. Phase I/II study of bortezomib in combination with carboplatin and bevacizumab as first line therapy in patients with advanced non-small cell lung cancer (NSCLC)

    PubMed Central

    Piperdi, Bilal; Walsh, William V; Bradley, Kendra; Zhou, Zheng; Bathini, Venu; Hanrahan-Boshes, Meredith; Hutchinson, Lloyd; Perez-Soler, Roman

    2013-01-01

    Purpose To establish the maximum tolerated dose (MTD) of weekly bortezomib in combination with fixed standard doses of carboplatin and bevacizumab and to estimate the efficacy (response rate and progression free survival) and safety of combination therapy with carboplatin, bortezomib and bevacizumab as first line therapy in patients with advanced NSCLC. Experimental Design Patients were assigned to three dose levels of weekly bortezomib with the fixed standard doses of carboplatin (AUC 6) and bevacizumab (15 mg/kg) q 3 wks using a standard phase I design. Bortezomib doses were 1.3 mg/m21.6 mg/m2 and 1.8 mg/m2 weekly on D1 and D8 of q 3wk cycle. A maximum of six cycles was administered. Patients with complete, partial response (PR) or stable disease were continued on single agent bevacizumab (15 mg/kg q 3 wks) as maintenance therapy. In phase II, either level III or MTD was administered to evaluate the efficacy and safety of the combination in first line treatment of advanced NSCLC. Results 16 patients were enrolled (3, 4 and 9 pts in dose level I, II and III respectively). There was no pre-defined dose limiting toxicity in cycle 1 in all 16 patients. The recommended phase II dose is bortezomib 1.8 mg/m2 weekly on day 1 and day 8 in combination with carboplatin AUC of 6 and bevacizumab 15 mg/kg on every 21 day cycle. Total of 9 patients were treated at the recommended phase II dose level. The most common treatment related grade 3/4 toxicities during the subsequent cycles were thrombocytopenia (58%), lymphopenia (25%), neutropenia (12%) and diarrhea (25%). The grade 1/2 neuropathy was seen in 7 out of 16 pts (44%). The response rate, PFS and OS in all patients were 37.5% (95%CI 13.8% - 61.2%), 5.0 months (m) (95%CI: 3.1-8.4), 9.9 m (95% CI: 8.2-14.1) and the 9 patients in phase II portion are 44% (95%CI 15.3% - 77.3%), 5.5 m (95%CI: 3.1-12.2) and 10.9 months (95%CI: 8.0-14.1). Conclusion The recommended phase II dose for this combination is: carboplatin AUC 6

  19. A chromatographic estimate of the degree of surface heterogeneity of RPLC packing materials. III. Endcapped amido-embedded reversed phase

    SciTech Connect

    Gritti, Fabrice; Guiochon, Georges A

    2006-01-01

    The difference in adsorption behavior between a conventional monomeric endcapped C{sub 18} stationary phase (3.43 {micro}mol/m{sup 2}) and an endcapped polymeric RP-Amide phase (3.31 {micro}mol/m{sup 2}) was investigated. The adsorption isotherms of four compounds (phenol, caffeine, sodium 2-naphthalene sulfonate, and propranololium chloride) were measured by frontal analysis (FA) and the degree of heterogeneity of each phase for each solute was characterized by their adsorption energy distributions (AED), derived using the Expectation-Maximization method. The results show that only certain analytes (phenol and 2-naphthalene sulfonate) are sensitive to the presence of the polar embedded amide groups within the RP phase. Their binding constants on the amide-bonded phase are significantly higher than on conventional RPLC phases. Furthermore, an additional type of adsorption sites was observed for these two compounds. However, these sites having a low density, their presence does not affect much the retention factors of the two analytes. On the other hand, the adsorption behavior of the other two analytes (caffeine and propranololium chloride) is almost unaffected by the presence of the amide group in the bonded layer. Strong selective interactions may explain these observations. For example, hydrogen-bond interactions between an analyte (e.g., phenol or naphthalene sulfonate) and the carbonyl group (acceptor) or the nitrogen (donor) of the amido-embedded group may take place. No such interactions may take place with either caffeine or the cation propranololium chloride. This study confirms the hypothesis that analytes have ready access to locations deep inside the bonded layer, where the amide groups are present.

  20. Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study

    PubMed Central

    Chen, San-Chi; Chang, Peter Mu-Hsin

    2016-01-01

    Lessons Learned Cisplatin/tegafur/uracil/irinotecan triple combination therapy shows moderate response, especially in patients without previous chemoradiotherapy within the 6 months before this combination therapy. Toxicity is tolerable, and quality of life is improved in responders. Background. The prognosis is poor in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Triple combination therapy may increase tumor response. Methods. This phase I/II prospective trial first determined the dose-limiting toxicity and recommended dose of irinotecan with cisplatin and tegafur/uracil (UFUR) in phase I. Irinotecan was supplied at doses of 40, 50, 60, and 70 mg/m2 by using a standard 3+3 design. Doses of cisplatin and UFUR were held stable. In phase II, the recommended dose of irinotecan was administered intravenously (i.v.) over 90 min on day 1, with cisplatin 50 mg/m2 i.v. over 60 min also on day 1, and oral UFUR 200 mg twice a day for 5 days every 2 weeks a cycle. Results. In the phase I portion, 14 patients were enrolled, and the dose level of irinotecan at 60 mg/m2 was defined as the recommended dose for the phase II portion of the study. Among 43 patients enrolled in the phase II portion, complete response was seen in 2 patients (4.7%) and partial response in 10 patients (23.3%), and the disease control rate was 39.5%. In a subgroup analysis of patients whose prior chemoradiotherapy was more than 6 months earlier, a response rate of 40.7% and disease control rate of 59.3% were observed. Conclusion. Cisplatin/UFUR/irinotecan triple combination therapy is tolerated and effective for selected patients. Individualized choice of treatment will influence prognosis and quality of life in R/M HNSCC patients. PMID:27091418

  1. "Brief Report: Increase in Production of Spoken Words in Some Children with Autism after PECS Teaching to Phase III"

    ERIC Educational Resources Information Center

    Carr, Deborah; Felce, Janet

    2007-01-01

    The context for this work was an evaluation study [Carr, D., & Felce, J. A. (in press)] of the early phases of the Picture Exchange Communication System (PECS) [Frost, L. A., & Bondy, A. S. (1994). "The picture exchange communication system training manual." Cherry Hill, NJ: Pyramid Educational Consultants, Inc.; Frost, L. A., & Bondy, A. S.…

  2. Sensitive determination of As (III) and As (V) by magnetic solid phase extraction with Fe@polyethyleneimine in combination with hydride generation atomic fluorescence spectrometry.

    PubMed

    Zhou, Qingxiang; Zheng, Zhenwen; Xiao, Junping; Fan, Huili

    2016-08-15

    The magnetic nanomaterial Fe@polyethyleneimine (Fe@PEI) was successfully synthesized and used as an effective adsorbent material for magnetic solid phase extraction(MSPE) of As(III) and As(V) from water samples. Fe@SiO2 nanoparticles were prepared by one pot synthetic method using a borohydride reduction method, then modified with (3-chloropropyl)trimethoxysilane to obtain Fe@SiO2-Cl by chloropropylation, which was reacted with PEI to achieve Fe@polyethyleneimine (Fe@PEI). The microstructure and morphology of Fe@PEI were characterized by transmission electron microscoscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). The experimental results showed that Fe@PEI demonstrated excellent adsorption for As(III) and As(V). Based on this fact, the determination method for these two arsenic species earned good limits of detection (LODs) of 0.002μgL(-1) and wide calibration curves in the concentration range from 0.008 to 0.2μgL(-1). The precisions of As (III) and As (V)were 1.95% and 2.55% (RSD, n=6), respectively. The proposed method was validated with real samples and the spiked recoveries were in the range of 82.7-98.3% and the accuracies were in the range of 2-13.3%. The results demonstrated that the developed MSPE method had good advantages such as simplicity, rapid separation, low cost, easy to reuse and high-quality analytical performances, which made it attractive for rapid and efficient extraction of inorganic arsenic species in the environmental water samples. PMID:27260453

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

    PubMed Central

    Harenberg, Anke; de Montfort, Aymeric; Jantet-Blaudez, Frédérique; Bonaparte, Matthew; Boudet, Florence; Saville, Melanie; Jackson, Nicholas; Guy, Bruno

    2016-01-01

    Background 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). Methodology/Principal findings 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. Conclusions/Significance These exploratory findings show that CYD-TDV does not induce a particular immune profile versus placebo, corroborating the clinical profile observed. PMID:27459266

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

    NASA Technical Reports Server (NTRS)

    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.

  5. A phase I/II study of the pan Bcl-2 inhibitor obatoclax mesylate plus bortezomib for relapsed or refractory mantle cell lymphoma

    PubMed Central

    Goy, André; Hernandez-Ilzaliturri, Francisco J.; Kahl, Brad; Ford, Peggy; Protomastro, Ewelina; Berger, Mark

    2015-01-01

    Obatoclax, a BH3 mimetic inhibitor of anti-apoptotic Bcl-2 proteins, demonstrates synergy with bortezomib in preclinical models of mantle cell lymphoma (MCL). This phase I/II study assessed obatoclax plus bortezomib in patients with relapsed/refractory MCL. Twenty-three patients received obatoclax 30 or 45 mg plus bortezomib 1.0 or 1.3 mg/m2, administered intravenously on days 1, 4, 8 and 11 of a 21-day cycle. In phase I, the combination was feasible at all doses. Obatoclax 45 mg plus bortezomib 1.3 mg/m2 was selected for phase II study. Common adverse events were somnolence (87%), fatigue (61%) and euphoric mood (57%), all primarily grade 1/2. Grade 3/4 events included thrombocytopenia (21%), anemia (13%) and fatigue (13%). Objective responses occurred in 4/13 (31%) evaluable patients (three complete and one partial response). Six patients (46%) had stable disease lasting ≥ 8 weeks. Obatoclax plus bortezomib was feasible, but the synergy demonstrated in preclinical models was not confirmed. PMID:24679008

  6. Integrated Sensing & Controls for Coal Gasification - Development of Model-Based Controls for GE's Gasifier & Syngas Cooler. Topical Rerport for Phase III

    SciTech Connect

    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.

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

    SciTech Connect

    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.

  8. Disposable terbium (III) salicylate complex imprinted membrane using solid phase surface fluorescence method for fast separation and detection of salicylic acid in pharmaceuticals and human urine.

    PubMed

    Huang, Jianxiang; Hu, Yufei; Hu, Yuling; Li, Gongke

    2013-03-30

    In this work, a simple, low cost, selective and sensitive complex imprinted membrane (CIM) for solid-phase fluorescent detection was developed with terbium (III) salicylate as complex template. Terbium-sensitized luminescence was employed for monitoring salicylic acid (SA) based on the fluorescence enhancement effect of benzoic acid derivatives on lanthanide ion Tb (III). The resulting CIM showed good fluorescent response and high selectivity towards SA with Tb as pivot in protic solvents, while demonstrating better analytical performance than the controlled membranes. The optimized adsorption time was 10 min, indicating rapid kinetics of the imprinted membrane. The linear response of CIM to SA was from 0.20 to 10mg/L with limit of detection (LOD) of 0.040 mg/L. The prepared CIM was successfully applied to the analysis of salicylic acid in pharmaceuticals and spiked human urine with recoveries of 80.6%-88.1%. The analytical results of the proposed method were in good agreement with those obtained by high performance liquid chromatography (HPLC) method, indicating that the developed membrane has acceptable practicability for fast determination of SA in real samples.

  9. Phase Equilibrium Experiments at 0.5 GPa and 1100-1300 deg. C on a Basaltic Andesite From Arenal Volcano, Costa Rica.

    NASA Astrophysics Data System (ADS)

    Pertermann, M.; Lundstrom, C. C.

    2004-12-01

    The on-going eruption of Arenal volcano has undergone complex changes in eruptive behavior. To investigate pre-eruptive crustal processes, we conducted phase equilibrium experiments on a basaltic andesite. The anhydrous synthetic starting mix has a Mg# of 52 and concentrations of SiO2, Na2O and K2O of 55, 3.0 and 0.6 wt.%, respectively. Al(OH)3 was used to obtain bulk water concentrations of 2 and 4 wt.%. Starting mixes were loaded into Pt/C capsules and each run contained three capsules with nominal water contents of 0, 2, and 4 wt.%. Experiments were run in a piston-cylinder apparatus with NaCl/pyrex/MgO assemblies and S-type thermocouples. Water loss is a potential problem in wet experiments: the actual water contents in quenched glasses remain to be quantified and results presented here are only from runs in which melt fractions systematically increased with initial water content at a given constant temperature. At 1300° C the dry composition yields glass coexisting with traces of spinel and plag, and both hydrous compositions are above the liquidus. Glass, plag (An75-82) and traces of spinel are present for all three compositions at 1250° C. At 1200° C, cpx is present in the dry composition with plag and glass; increasing water content enhances the plag stability (An77-69) at the expense of cpx, which is replaced by low-Ca pyroxene. Traces of spinel are present and are found in all experiments at lower temperatures, independent of water content. Cpx, low-Ca pyroxene, plag and andesitic glass are present at 1150° C in the dry and 2% water compositions, but the 4% water composition yields only cpx and no low-Ca pyroxene. Due to the overall small grain size (¡Ü10 μ m) in our experiments, low-Ca pyroxene may have been overlooked, yet the lower plag mode and its decreasingly anorthitic character (An64-59) may account for the absence of low-Ca pyroxene. At 1100° C, glasses become dacitic to rhyolitic and coexist with low-An plag and cpx, and in the case of

  10. Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

    PubMed Central

    Hamilton, Betty K.; Rosen, Mark A.; Amaravadi, Ravi K.; Schuchter, Lynn M.; Gallagher, Maryann; Chen, Helen; Sehgal, Chandra; O’Dwyer, Peter J.

    2015-01-01

    Background. Vascular endothelial growth factor and platelet-derived growth factor signaling in the tumor microenvironment appear to cooperate in promoting tumor angiogenesis. Patients and Methods. We conducted a phase I trial combining bevacizumab (i.v. every 2 weeks) and imatinib (oral daily). Once a recommended phase II dose combination was established, a phase II trial was initiated in patients with metastatic melanoma. A Simon 2-stage design was used with 23 patients required in the first stage and 41 patients in total should the criteria to proceed be met. We required that 50% of the patients be progression-free at 16 weeks. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and power Doppler ultrasonography were performed in patients with metastatic tumors amenable to imaging with these methods at baseline and after 4 weeks. Results. A total of 17 patients were accrued to 4 dose and combination levels. Bevacizumab 10 mg/kg every 2 weeks could be safely combined with imatinib 800 mg daily. Common toxicities included fatigue, nausea, vomiting, edema, proteinuria, and anemia, but were not commonly severe. A total of 23 patients with metastatic melanoma (48% with American Joint Commission on Cancer stage M1c; median age, 63 years) were enrolled in the first stage of phase II. The 16-week progression-free survival rate was 35%, leading to termination of phase II after the first stage. In the small subset of patients who remained on study with lesions evaluable by DCE-MRI, significant decreases in tumor vascular permeability were noted, despite early disease progression using the Response Evaluation Criteria In Solid Tumors. Conclusion. Bevacizumab and imatinib can be safely combined at the maximum doses used for each agent. We did not observe significant clinical activity with this regimen in melanoma patients. Implications for Practice: Vascular endothelial growth factor (VEGF)-targeted antiangiogenic therapy has proven clinical efficacy as a

  11. K1-95-HW, cruise report 1995: preliminary results. Phase III: sediment chemistry and biological sampling survey

    USGS Publications Warehouse

    Torresan, M.E.; Hampton, M.A.; Barber, J.H.; Wong, F.L.

    1995-01-01

    Mamala Bay, off the south shore of the island of Oahu, has been used as a repository of dredged material primarily from Pearl and Honolulu Harbors for over a century. The U.S. Geological Survey, U.S. Army Corps of Engineers, and the U.S. Environmental Protection Agency are conducting an integrated study on the distribution and character of dredged materials as well as the effects of dredged material on the marine environment. A three phase study is providing information to evaluate the effects on seafloor substrate and the benthic fauna. The studies include geophysical profiling and imaging, bottom photography, sampling, chemical and physical analyses of sediment, and evaluations of the benthic population, population density, and adverse impacts to the benthic fauna. Phase 1, conducted in 1993, inventoried the seafloor via remote sensing. Sidescan sonar and subbottom profilers characterized the seafloor in and around the disposal sites, and the resulting products reveal the character and extent of the dredged material. These data were used to plan Phase 2 in 1994, a sampling program that employed subbottom profilers, video and still photography, and seafloor sampling to ground truth the sonar mosaic and identify the seafloor substrates responsible for the various acoustic signatures on the sonar images and subbottom profiles. Box coring provided the samples necessary to distinguish dredged material from native sediment, and for the chemical analyses used to determine contaminant concentrations. Phase 3 studies conducted in June of 1995 consisted of box core sampling for chemical and biological analyses. Specific studies include: infaunal taxonomy and population density, bioassay/bioaccumulation, sediment chemistry, and post-disposal resuspension and transport. The 1995 survey, conducted June 14 through 17, resulted in the collection of 39 box cores from 20 different stations. Multiple box cores were composited at 7 different locations occupied in 1994, to provide

  12. Decitabine reduces transfusion dependence in older patients with acute myeloid leukemia: results from a post hoc analysis of a randomized phase III study.

    PubMed

    He, Jianming; Xiu, Liang; De Porre, Peter; Dass, Ramesh; Thomas, Xavier

    2015-04-01

    This post hoc analysis of the DACO-016 phase III study evaluates the impact of decitabine on transfusion dependence and survival in 485 elderly patients with newly diagnosed acute myeloid leukemia (AML). Red blood cell (RBC) and platelet (PLT) transfusion independence, defined as no transfusions for ≥ 8 consecutive weeks, was measured in both decitabine (n = 242) and treatment choice (TC, n = 243) arms. More RBC transfusion dependent patients at baseline became transfusion independent with decitabine than with TC (26% vs. 13%; p = 0.0026). Similar results were obtained for patients who were PLT transfusion dependent at baseline (31% vs. 13%; p = 0.0069). When excluding patients who attained complete remission (CR), survival was improved in patients who achieved RBC or PLT transfusion independence, suggesting that reaching CR is not a prerequisite for deriving benefit from treatment with decitabine. In addition, patients who achieved transfusion independence with decitabine had increased treatment continuation, even in the absence of CR.

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

    SciTech Connect

    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.

  14. Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results.

    PubMed

    Cohen, Alexander T; Imfeld, Stephan; Rider, Thomas

    2014-05-01

    The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.

  15. TEAMS: Toxicity- and Efficacy-based Dose Insertion Design with Adaptive Model Selection for Phase I/II Dose-Escalation Trials in Oncology

    PubMed Central

    Guo, Wentian; Ni, Yang; Ji, Yuan

    2015-01-01

    Summary In many oncology clinical trials it is necessary to insert new candidate doses when the prespecified doses are poorly elicited. Formal statistical designs with dose insertion are lacking. We propose a dose insertion design for phase I/II clinical trials in oncology based on both efficacy and toxicity outcomes. We also implement Bayesian model selection during the course of the trial so that better models can be adaptively chosen to achieve more accurate inference. The new design, TEAMS, achieves great operating characteristics in extensive simulation studies due to its ability to adaptively insert new doses as well as perform model selection. As a result, appropriate doses are inserted when necessary and desirable doses are selected with higher probabilities at the end of the trial. PMID:26528377

  16. A Prospective Randomised Phase III Clinical Trial Testing the Role of Prophylactic Cranial Radiotherapy in Patients Treated with Trastuzumab for Metastatic Breast Cancer - Anglo Celtic VII.

    PubMed

    Canney, P; Murray, E; Dixon-Hughes, J; Lewsley, L-A; Paul, J

    2015-08-01

    A high incidence of central nervous system (CNS) metastases has been reported in patients with HER2-positive tumours receiving trastuzumab therapy for metastatic breast cancer. This study tested whether prophylactic cranial irradiation (PCI) could reduce the incidence of CNS metastases in this setting. This was a prospective, randomised phase III trial. Patients were randomised 1:1 to no PCI or PCI delivered at around 6 weeks after study entry. Cognitive function was assessed prospectively. In total, 51 patients were randomised over a 3 year period; 25 received PCI and 26 did not. The cumulative incidence of CNS metastases at 2 years was 32.4% (standard error = 9.8%) on the no PCI arm and 21.0% (standard error = 8.6%) on the PCI arm; the associated hazard ratio was 0.57 (95% confidence interval 0.18-1.74; P = 0.32). There was no evidence of cognitive dysfunction in PCI patients.

  17. Estimation of drug cost avoidance and pathology cost avoidance through participation in NCIC Clinical Trials Group phase III clinical trials in Canada

    PubMed Central

    Tang, P.A.; Hay, A.E.; O’Callaghan, C.J.; Mittmann, N.; Chambers, C.R.; Pater, J.L.; Leighl, N.B.

    2016-01-01

    Background Cost avoidance occurs when, because of provision of a drug therapy [drug cost avoidance (dca)] or a pathology test [pathology cost avoidance (pca)] during trial participation, health care payers need not pay for standard treatments or testing. The aim of our study was to estimate the total dca and pca for Canadian patients enrolled in relevant phase iii trials conducted by the ncic Clinical Trials Group. Methods Phase iii trials that had completed accrual and resulted in dca or pca were identified. The pca was calculated based on the number of patients screened and the test cost. The dca was estimated based on patients randomized, the protocol dosing regimen, drug cost, median dose intensity, and median duration of therapy. Costs are presented in Canadian dollars. No adjustment was made for inflation. Results From 1999 to 2011, 4 trials (1479 patients) resulted in pca and 17 trials (3195 patients) resulted in dca. The total pca was estimated at $4,194,849, which included testing for KRAS ($141,058), microsatellite instability ($18,600), and 21-gene recurrence score ($4,035,191). The total dca was estimated at $27,952,512, of which targeted therapy constituted 43% (five trials). The combined pca and dca was $32,147,361. Conclusions Over the study period, trials conducted by the ncic Clinical Trials Group resulted in total cost avoidance (pca and dca) of approximately $7,518 per patient. Although not all trials lead to cost avoidance, such savings should be taken account when the financial impact of conducting clinical research is being considered. PMID:26985151

  18. The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

    SciTech Connect

    Vuong, Te; Waschke, Kevin; Niazi, Tamim; Richard, Carole; Parent, Josee; Liberman, Sender; Mayrand, Serge; Loungnarath, Rasmy; Stein, Barry; Devic, Slobodan

    2011-08-01

    Purpose: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). Methods and Materials: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. Results: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). Conclusions: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

  19. 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

    PubMed Central

    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

  20. Surface decoration of amine-rich carbon nitride with iron nanoparticles for arsenite (As(III)) uptake: The evolution of the Fe-phases under ambient conditions.

    PubMed

    Georgiou, Y; Mouzourakis, E; Bourlinos, A B; Zboril, R; Karakassides, M A; Douvalis, A P; Bakas, Th; Deligiannakis, Y

    2016-07-15

    A novel hybrid material (gC3N4-rFe) consisting of amine-rich graphitic carbon nitride (gC3N4), decorated with reduced iron nanoparticles (rFe) is presented. XRD and TEM show that gC3N4-rFe bears aggregation-free Fe-nanoparticles (10nm) uniformly dispersed over the gC3N4 surface. In contrast, non-supported iron nanoparticles are strongly aggregated, with non-uniform size distribution (20-100nm). (57)Fe-Mössbauer spectroscopy, dual-mode electron paramagnetic resonance (EPR) and magnetization measurements, allow a detailed mapping of the evolution of the Fe-phases after exposure to ambient O2. The as-prepared gC3N4-rFe bears Fe(2+) and Fe° phases, however only after long exposure to ambient O2, a Fe-oxide layer is formed around the Fe° core. In this [Fe°/Fe-oxide] core-shell configuration, the gC3N4-rFe hybrid shows enhanced As(III) uptake capacity of 76.5mgg(-1), i.e., ca 90% higher than the unmodified carbonaceous support, and 300% higher than the non-supported Fe-nanoparticles. gC3N4-rFe is a superior As(III) sorbent i.e., compared to its single counterparts or vs. graphite/graphite oxide or activated carbon analogues (11-36mgg(-1)). The present results demonstrate that the gC3N4 matrix is not simply a net that holds the particles, but rather an active component that determines particle formation dynamics and ultimately their redox profile, size and surface dispersion homogeneity.

  1. Phase I-II Trial of Cetuximab, Capecitabine, Oxaliplatin, and Radiotherapy as Preoperative Treatment in Rectal Cancer

    SciTech Connect

    Roedel, Claus Arnold, Dirk; Hipp, Matthias; Liersch, Torsten; Dellas, Kathrin; Iesalnieks, Igors; Hermann, Robert Michael; Lordick, Florian; Hohenberger, Werner; Sauer, Rolf

    2008-03-15

    Purpose: To evaluate the safety and activity of preoperative radiotherapy (RT) with concurrent cetuximab, capecitabine, and oxaliplatin in rectal cancer patients. Patients and Methods: A total of 60 patients with rectal cancer (T3-T4 or N+, M1 allowed) entered the trial at five investigator sites; the data from 58 patients were assessable. Cetuximab was given as an initial dose of 400 mg/m{sup 2} 7 days before the start of RT, and then at 250 mg/m{sup 2} once weekly during RT (50.4 Gy in 28 fractions). Capecitabine and oxaliplatin were administered according to an established schedule of oxaliplatin (50 mg/m{sup 2} on Days 1, 8, 22, and 29) and capecitabine (Days 1-14 and 22-35) at three dose levels: 1,000, 1,300, and 1,650 mg/m{sup 2}/d during the Phase I part of the study. The main endpoint of the Phase II was the pathologic complete response rate. Results: Thirteen patients were included in the Phase I part of the study, and the maximal tolerated dose was not reached. Overall, 48 patients were treated at the recommended dose of capecitabine (1,650 mg/m{sup 2}) and 45 patients (94%) underwent surgery. A pathologic complete response was observed in 4 patients (9%), and moderate (n = 12), minimal (n = 10), and no tumor regression (n = 2) was noted in 24 (53%) of 45 patients. The mean radiation dose intensity, cetuximab, capecitabine, oxaliplatin was 98%, 95%, 94%, and 94%, respectively. The incidence of Grade 3-4 diarrhea was restricted to 19%. Postoperative complications of any grade occurred in 33% of patients. Conclusions: The results of our study have shown that cetuximab can be combined safely with capecitabine and oxaliplatin plus RT. The low pathologic complete response rate achieved should stimulate additional preclinical investigations to establish the best sequence of triple combinations.

  2. Linear canonical transformations of coherent and squeezed states in the Wigner phase space. III - Two-mode states

    NASA Technical Reports Server (NTRS)

    Han, D.; Kim, Y. S.; Noz, Marilyn E.

    1990-01-01

    It is shown that the basic symmetry of two-mode squeezed states is governed by the group SP(4) in the Wigner phase space which is locally isomorphic to the (3 + 2)-dimensional Lorentz group. This symmetry, in the Schroedinger picture, appears as Dirac's two-oscillator representation of O(3,2). It is shown that the SU(2) and SU(1,1) interferometers exhibit the symmetry of this higher-dimensional Lorentz group. The mathematics of two-mode squeezed states is shown to be applicable to other branches of physics including thermally excited states in statistical mechanics and relativistic extended hadrons in the quark model.

  3. Silicon materials task of the low cost solar array project (Phase III). Effects of impurities and processing on silicon solar cells. Phase III summary and seventeenth quarterly report, Volume 2: analysis of impurity behavior

    SciTech Connect

    Hopkins, R.H.; Davis, J.R.; Rohatgi, A.; Campbell, R.B.; Blais, P.D.; Rai-Choudhury, P.; Stapleton, R.E.; Mollenkopf, H.C.; McCormick, J.R.

    1980-01-23

    The object of this phase of the program has been to investigate the effects of various processes, metal contaminants and contaminant-process interactions on the properties of silicon and on the performance of terrestrial silicon solar cells. The study encompassed topics including thermochemical (gettering) treatments, base doping concentration, base doping type (n vs. p), grain boundary-impurity interaction, non-uniformity of impurity distribution, long term effects of impurities, as well as synergic and complexing phenomena. The program approach consists in: (1) the growth of doubly and multiply-doped silicon single crystals containing a baseline boron or phosphorus dopant and specific impurities which produce deep levels in the forbidden band gap; (2) assessment of these crystals by chemical, microstructural, electrical and solar cell tests; (3) correlation of the impurity type and concentration with crystal quality and device performance; and (4) delineation of the role of impurities and processing on subsequent silicon solar cell performance. The overall results reported are based on the assessment of nearly 200 silicon ingots. (WHK)

  4. Systematic review and meta-analysis of phase I/II targeted therapy combined with radiotherapy in patients with glioblastoma multiforme: quality of report, toxicity, and survival.

    PubMed

    dos Santos, Marcos A; Pignon, Jean-Pierre; Blanchard, Pierre; Lefeuvre, Delphine; Levy, Antonin; Touat, Mehdi; Louvel, Guillaume; Dhermain, Frédéric; Soria, Jean-Charles; Deutsch, Eric; Le Teuff, Gwénaël

    2015-06-01

    To perform a systematic review and meta-analysis of severe adverse events (SAE) reported in early trials combining molecularly targeted therapies (MTT) with radiotherapy (RT), and to compare them to standard therapy. A summary data meta-analysis was performed and compared to the historical standard. Inclusion criteria were phase I and/or II trials published between 2000 and 2011, with glioblastoma multiforme patients treated with RT and MTT. Pooled incidence rates (IR) of SAE were estimated as well as the pooled median progression-free survival (PFS) and overall survival (OS). Nineteen prospective trials (9 phase I, 1 phase I/II and 9 phase II) out of 29 initially selected were included (n = 755 patients). The exact number of patients who had experienced SAE was mentioned in 37 % of the trials, concerning only 17 % of the patients. Information such as the period during which adverse events were monitored, the planned treatment duration, and late toxicity were not reported in the trials. The pooled IR of overall SAE was 131.2 (95 % CI 88.8-193.7) per 1000 person-months compared to 74.7 (63.6-87.8) for standard therapy (p < 0.01). Significant differences were observed for gastrointestinal events (p = 0.05) and treatment-related deaths (p = 0.02), in favour of standard therapy. No significant difference was observed in PFS and OS. Reporting a summary of toxicity data in early clinical trials should be stringently standardized. The use of MTT with RT compared to standard therapy increased SAE while yielded comparable survival in glioblastoma multiforme patients.

  5. Phase II Results of RTOG 0537: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

    PubMed Central

    Wong, Raimond K. W.; James, Jennifer L.; Sagar, Stephen; Wyatt, Gwen; Nguyen-Tân, Phuc Felix; Singh, Anurag K.; Lukaszczyk, Barbara; Cardinale, Francis; Yeh, Alexander M.; Berk, Lawrence

    2011-01-01

    Purpose This phase II component of a multi-institutional phase II/III randomized trial assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Methods Head and neck cancer patients who were 3–24 months from completing radiotherapy ± chemotherapy (RT±C) and experiencing xerostomia symptoms with basal whole saliva production ≥0.1 ml/min and without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 over 12 weeks) using a Codetron™ unit. The primary objective assessed the feasibility of ALTENS treatment. A patient was considered compliant if 19/24 ALTENS were delivered, with a targeted 85% compliance rate. Secondary objectives measured treatment-related toxicities and ALTENS effect on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Results Of 48 accrued patients, 47 were evaluable. Median age was 60 years; 84% were male, 70% completed RT±C for > 12 months and 21% had received prior pilocarpine. All ALTENS sessions were completed in 34 patients, but 9 and 1 completed 20–23 and 19 sessions respectively, representing a 94% total compliance rate. 6-month XeQOLS scores were available for 35 patients; 30 (86%) achieved a positive treatment response with a mean reduction of 35.9% (SD 36.1). Five patients developed grade 1–2 gastrointestinal toxicity and one had grade 1 pain event. Conclusions ALTENS treatment for radiation-induced xerostomia can be uniformly delivered in a cooperative multicenter setting and has possible beneficial treatment response. Given these results, the phase III component of this study was initiated. PMID:22252927

  6. The Relativistic Heavy Ion Collider (RHIC) Refrigerator System at Brookhaven National Laboratory: Phase III of the System Performance and Operations Upgrades for 2006

    SciTech Connect

    A. Sidi-Yekhlef; R. Than; J. Tuozzolo; V. Ganni; P. Knudsen; D. Arenius

    2006-05-01

    An ongoing program at Brookhaven National Laboratory (BNL) consists of improving the efficiency of the Relativistic Heavy Ion Collider (RHIC) cryogenic system and reducing its power consumption. Phase I and II of the program addressed plant operational improvements and modifications that resulted in substantial operational cost reduction and improved system reliability and stability, and a compressor input power reduction of 2 MW has been demonstrated. Phase III, now under way, consists of plans for further increasing the efficiency of the plant by adding a load ''wet'' turbo-expander and its associated heat exchangers at the low temperature end of the plant. This additional stage of cooling at the coldest level will further reduce the required compressor flow and therefore compressor power input. This paper presents the results of the plant characterization, as it is operating presently, as well as the results of the plant simulations of the various planned upgrades for the plant. The immediate upgrade includes the changes associated with the load expander. The subsequent upgrade will involve the resizing of expander 5 and 6 to increase their efficiencies. The paper summarizes the expected improvement in the plant efficiency and the overall reduction in the compressor power.

  7. [Determination of sodium iron (III) ethylenediaminetetraacetate in iron-fortified soy sauce by reversed-phase ion-pair high performance liquid chromatography].

    PubMed

    Wei, Feng; Li, Wenxian; Huang, Jian; Huo, Junsheng; Sun, Jing

    2006-01-01

    A novel reversed-phase ion-pair high performance liquid chromatographic method was developed for separation and determination of sodium iron (III) ethylenediaminetetraacetate (NaFeEDTA) in iron-fortified soy sauce. Sample treatment and chromatographic conditions were investigated. After precipitation by methanol, the sample was separated on a Zorbax C8 column (150 mm x 4.6 mm i. d., 5 microm). The mobile phase was 12.5% (v/v) methanol solution containing 0.13% (v/v) tetrabutyl ammonium hydroxide and 0.052% (v/v) formic acid ( pH 3.5). NaFeEDTA was detected at 254 nm. The separation was achieved within 30 min with a flow rate of 1.00 mL/min. An iron-fortified soy sauce sample containing 2.00 g/L NaFeEDTA was analyzed for 6 times, and the relative standard deviation (RSD) of peak areas of NaFeEDTA was 0. 89%. The recoveries of NaFeEDTA ranged from 94.15% to 101.5% with the spiked amounts of 0.50 - 4.00 g/L. The detection limit of NaFeEDTA standard solution was 0.03 mg/L. This simple and rapid method with good reproducibility can be used for the determination of NaFeEDTA in iron-fortified soy sauce.

  8. Randomized Phase III study of gemcitabine plus S-1 versus gemcitabine plus cisplatin in advanced biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1113, FUGA-BT).

    PubMed

    Mizusawa, Junki; Morizane, Chigusa; Okusaka, Takuji; Katayama, Hiroshi; Ishii, Hiroshi; Fukuda, Haruhiko; Furuse, Junji

    2016-04-01

    A Phase II selection design trial was conducted to identify the most promising regimen for comparison with standard therapy in chemo-naive patients with unresectable or recurrent biliary tract cancer (JCOG0805). Gemcitabine plus S-1 therapy showed better efficacy than S-1 monotherapy with acceptable safety in JCOG0805 study. Based on this result, a randomized Phase III trial was started in May 2013 to confirm the non-inferiority of gemcitabine plus S-1 therapy relative to gemcitabine plus cisplatin therapy, which is the current standard treatment for chemo-naive patients with unresectable or recurrent biliary tract cancer. A total of 350 patients will be accrued from 32 Japanese institutions within 4 years. The primary endpoint is overall survival, while the secondary endpoints are progression-free survival, adverse events, serious adverse events, clinically significant adverse events, response rate and %planned dose. This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm) and the registration number is UMIN000010667.

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

    SciTech Connect

    Leitzinger, Eric J.

    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.

  10. Microseismic monitoring for evidence of geothermal heat in the capital district of New York. Final report, Phases I-III

    SciTech Connect

    Not Available

    1983-06-01

    The seismic monitoring work of the geothermal project was initiated for the purpose of determining more exactly the relationship between seismicity and the postulated geothermal and related activity in the Albany-Saratoga Springs area in upstate New York. The seismic monitoring aspect of this work consisted of setting up and operating a network of seven seismograph stations within and around the study area capable of detecting and locating small earthquakes. To supplement the evidence from present day seismic activity, a list of all known historical and early instrumental earthquakes was compiled and improved from original sources for a larger region centered on the study area. Additional field work was done to determine seismic velocities of P and S phases by special recording of quarry blasts. The velocity results were used both as an aid to improve earthquake locations based on computer programs and to make inferences about the existence of temperature anomalies, and hence geothermal potential, at depths beneath the study area. Finally, the level in the continuous background earth vibration, microseisms, was measured throughout the study area to test a possibility that a relationship may exist at the surface between the level in microseisms and the geothermal or related activity. The observed seismic activity within the study area, although considerably higher (two to three times) than inferred from the historical and early instrumental data, is still not only low for a potential geothermal area but appears to be related to coherent regional tectonic stresses and not to the proposed more localized geothermal activity reflected in the mineralized, CO/sub 2/ rich spring discharge.

  11. Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy.

    PubMed

    Boye, Kjetil; Jacob, Havjin; Frikstad, Kari-Anne M; Nesland, Jahn M; Maelandsmo, Gunhild M; Dahl, Olav; Nesbakken, Arild; Flatmark, Kjersti

    2016-08-01

    Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population-representative cohort and a randomized phase III study on adjuvant 5-fluorouracil/levamisole. Sensitivity to treatment with 5-fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse-free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse-free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5-fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5-fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine-based chemotherapy is limited. PMID:27273130

  12. Effect of Protein Incorporation on the Nanostructure of the Bicontinuous Microemulsion Phase of Winsor-III Systems: A Small-Angle Neutron Scattering Study

    DOE PAGESBeta

    Hayes, Douglas G.; Gomez del Rio, Javier A.; Ye, Ran; Urban, Volker S.; Pingali, Sai Venkatesh; O’Neill, Hugh M.

    2015-01-20

    Small-angle neutron scattering (SANS) analysis using the Teubner₋Strey model has been employed to evaluate the effect of protein incorporation into the middle, bicontinuous microemulsion (BμE) phase of Winsor-III (WIII) systems formed by an aerosol-OT (AOT)/alkyl ethoxylate mixed surfactant system to understand better the extraction of proteins into and out of BμEs and to study the effect of proteins on a system that serves as a biomimetic analog of cell membranes. Under conditions of high salinity, the incorporation of positively charged proteins cytochrome c, lysozyme, and α-chymotrypsin, near their solubilization limit in the BμEs promoted the release of water and oilmore » from the BμEs, a decrease in the quasi-periodic repeat distance (d), an increase in ordering (a decrease in the amphiphilicity factor, fa) for the surfactant monolayers, and a decrease in the surface area per surfactant headgroup, suggesting that the proteins affected the self-assembly of components in the BμE phase and produced Debye shielding of AOTs sulfonate headgroup. For WIII systems possessing lower salinity, cytochrome c reduced the efficiency of surfactant in the BμE phase, noted by increases in d and fa, suggesting that the enzyme and AOT underwent ion pairing. We find that the results of this study demonstrate the importance of ionic strength to modulate proteinsurfactant interactions, which in turn will control the release of proteins encapsulated in the BμEs, relevant to WIII-based protein extraction and controlled release from BμE delivery systems, and demonstrate the utility of BμEs as a model system to understand the effect of proteins on biomembranes.« less

  13. Effects of Single Low Dose of Dexamethasone before Noncardiac and Nonneurologic Surgery and General Anesthesia on Postoperative Cognitive Dysfunction—A Phase III Double Blind, Randomized Clinical Trial

    PubMed Central

    Pereira, Valeria Fontenelle Angelim; Pietrobon, Ricardo S.; Schmidt, Andre P.; Oses, Jean P.; Portela, Luis V.; Souza, Diogo O.; Vissoci, João Ricardo Nickenig; da Luz, Vinicius Fernando; Trintoni, Leticia Maria de Araujo de Souza; Nielsen, Karen C.; Carmona, Maria José Carvalho

    2016-01-01

    Postoperative cognitive dysfunction (POCD) is a multifactorial adverse event most frequently in elderly patients. This study evaluated the effect of dexamethasone on POCD incidence after noncardiac and nonneurologic surgery. METHODS: One hundred and forty patients (ASA I-II; age 60–87 years) took part in a prospective phase III, double blind, randomized study involving the administration or not of 8 mg of IV dexamethasone before general anesthesia under bispectral index (BIS) between 35–45 or 46–55. Neuropsychological tests were applied preoperatively and on the 3rd, 7th, 21st, 90th and 180th days after surgery and compared with normative data. S100β was evaluated before and 12 hours after induction of anesthesia. The generalized estimating equations (GEE) method was applied, followed by the posthoc Bonferroni test considering P<0.05 as significant. RESULTS: On the 3rd postoperative day, POCD was diagnosed in 25.2% and 15.3% of patients receiving dexamethasone, BIS 35–45, and BIS 46–55 groups, respectively. Meanwhile, POCD was present in 68.2% and 27.2% of patients without dexamethasone, BIS 35–45 and BIS 46–55 groups (p<0.0001). Neuropsychological tests showed that dexamethasone associated to BIS 46–55 decreased the incidence of POCD, especially memory and executive function. The administration of dexamethasone might have prevented the postoperative increase in S100β serum levels. CONCLUSION: Dexamethasone can reduce the incidence of POCD in elderly patients undergoing surgery, especially when associated with BIS 46–55. The effect of dexamethasone on S100β might be related with some degree of neuroprotection. Trial Registration: www.clinicaltrials.gov NCT01332812 PMID:27152422

  14. Does Concurrent Radiochemotherapy Affect Cosmetic Results in the Adjuvant Setting After Breast-Conserving Surgery? Results of the ARCOSEIN Multicenter, Phase III Study: Patients' and Doctors' Views

    SciTech Connect

    Toledano, Alain H. . E-mail: alain.toledano@gmail.com; Bollet, Marc A.; Fourquet, Alain; Azria, David; Gligorov, Joseph; Garaud, Pascal; Serin, Daniel; Bosset, Jean-Francois; Miny-Buffet, Joelle; Favre, Anne; Le Foch, Olivier; Calais, Gilles

    2007-05-01

    Purpose: To evaluate the cosmetic results of sequential vs. concurrent adjuvant chemotherapy with radiotherapy after breast-conserving surgery for breast cancer, and to compare ratings by patients and physicians. Methods and Materials: From 1996 to 2000, 716 patients with Stage I-II breast cancers were included in a multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast-conserving surgery with axillary dissection, sequential treatment with chemotherapy first followed by radiotherapy vs. chemotherapy administered concurrently with radiotherapy. Cosmetic results with regard to both the overall aspect of the breast and specific changes (color, scar) were evaluated in a total of 214 patients (107 in each arm) by means of questionnaires to both the patient and a physician whose rating was blinded to treatment allocation. Results: Patients' overall satisfaction with cosmesis was not statistically different between the two arms, with approximately 92% with at least satisfactory results (p = 0.72), although differences between the treated and untreated breasts were greater after the concurrent regimen (29% vs. 14% with more than moderate differences; p 0.0015). Physician assessment of overall cosmesis was less favorable, with lower rates of at least satisfactory results in the concurrent arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall satisfaction with cosmesis between patients and doctors was only fair ({kappa} = 0.62). Conclusion: After breast-conserving surgery, the concurrent use of chemotherapy with radiotherapy is significantly associated with greater differences between the breasts. These differences do not translate into patients' lessened satisfaction with cosmesis.

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

    PubMed Central

    Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Matsusaka, Satoshi; Shinozaki, Eiji; Ozaka, Masato; Ogura, Mariko; Chin, Keisho; Yamaguchi, Toshiharu

    2015-01-01

    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 patients and diarrhea in five patients. There were no other severe adverse events or treatment-related deaths. Conclusion In mCRC patients with wild-type or heterozygous UGT1A1*6 or *28 genotype, biweekly XELIRI + BV is effective and feasible as second-line chemotherapy. Biweekly XELIRI + BV is considered a valid substitute for FOLFIRI

  16. A prevalidation study on the in vitro skin irritation function test (SIFT) for prediction of acute skin irritation in vivo: results and evaluation of ECVAM Phase III.

    PubMed

    Heylings, J R; Diot, S; Esdaile, D J; Fasano, W J; Manning, L A; Owen, H M

    2003-04-01

    A prevalidation study sponsored by the European Centre for the Validation of Alternative Methods (ECVAM) on in vitro tests for acute skin irritation is aimed at identifying non-animal tests capable of discriminating irritants (I) from non-irritants (NI), as defined according to European Union and OECD. This paper reports on Phase III for one of the methods, the skin integrity function test (SIFT), assessing the protocol performance of the SIFT, in terms of reproducibility and predictive ability, in three laboratories. The barrier function properties of excised mouse skin were determined using a set of 20 coded chemicals (10 I, 10 NI), using the endpoints of trans-epidermal water loss (TEWL) and electrical resistance (ER). The basis of the SIFT prediction model is if the ratios of the pre- and post-application values for either TEWL or ER are greater than five-fold, then the test chemical is deemed irritant (I). If the ratio of both parameters is less than five-fold then the chemical is deemed non-irritant (NI). Analysis of variance (ANOVA) indicated that the intra-lab reproducibility was acceptable but that the inter-lab reproducibility was not. Overall, the SIFT test under-predicted the irritancy of the test chemicals chosen for Phase III with an overall accuracy of only 55%. The sensitivity value (ability to correctly predict I) was only 30%. The specificity (ability to predict NI) of the test was better at 80%. A retrospective examination of the SIFT results was undertaken using Student's t-test and a significance level of P<0.05 to predict an irritant based on changes in the TEWL ratio values. This improved the predictivity of the SIFT test, giving a specificity of 60%, a sensitivity of 80% and an overall accuracy of 70%. Appropriate modifications to the prediction model have now been made and the SIFT will be re-examined in a new validation exercise to investigate the potential of this non-animal method to predict acute skin irritation potential. PMID:12650665

  17. Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma.

    PubMed

    Twelves, C; Boyer, M; Findlay, M; Cassidy, J; Weitzel, C; Barker, C; Osterwalder, B; Jamieson, C; Hieke, K

    2001-03-01

    Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.). Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v. 5-FU/LV. The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles. Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV. In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV. In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events. Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression. Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients. Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV. In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events. As anticipated with an oral home-based therapy

  18. 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

    PubMed Central

    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

  19. A phase I/II study to evaluate radiation therapy and hyperthermia for deep-seated tumours: a report of RTOG 89-08.

    PubMed

    Myerson, R J; Scott, C B; Emami, B; Sapozink, M D; Samulski, T V

    1996-01-01

    The purpose of this paper is to evaluate the safety and efficacy of deep hyperthermia in conjunction with radiation therapy. This study employed 'second generation' electromagnetic devices which were felt to be better able to confine heating and spare normal tissue than the devices evaluated in a previous study (RTOG 84-01). Sixty six patients at six institutions were enrolled on a prospective Phase I/II study. Eligible deep seated tumours were treated with a combination of external hyperthermia and radiation therapy. Radiation consisted of 1.7-2 Gy per fraction, 4-5 fractions per week, to > 20 Gy (previously irradiated lesions) or > 50 Gy (no previous radiation). Deep hyperthermia was delivered with electromagnetic devices: BSD 2000 for 92% of cases, Thermotron for 5% of cases, other low frequency electromagnetic for 4% of cases. Hyperthermia was delivered < or = twice weekly. Overall complete and partial response rates were 34% and 16% respectively. Response was not correlated with maximum tumour temperature or disease site. There was, however, a strong association with radiation dose: 54% CR with > or = 45 Gy versus 7% with < 45 Gy (p < 0.0001). The achieved temperatures were less than ideal. Although the average maximum tumor temperature was 41.9 degrees C (range 35.7 degrees C-46.7 degrees C), the minimum tumour temperatures were low. The average minimum tumour temperature was 38.5 degrees C and was never > 41.8 degrees C. Treatment was well tolerated with no fatalities. There were four acute grade 3 or 4 toxicities (6% of patients). Patient discomfort resulted in interruption or discontinuation of sessions in 30% of the sessions. In 12 cases (18% of patients) the planned course of hyperthermia was discontinued due to acute discomfort. The devices used in this study were better tolerated than the devices used in the previous Phase I/II deep hyperthermia trial (RTOG 84-01) with less patient discomfort and no problems with severe systemic cardiovascular stress

  20. A Model System for the Design and Maintenance of Related Instruction Curriculum for Approved U.S. Department of Labor Apprenticeship Programs; Phase III. Final Report and Final Evaluation Report.

    ERIC Educational Resources Information Center

    Lane Community Coll., Eugene, OR.

    A final report and final evaluation report of Phase III are provided for a project to establish a national clearinghouse for apprenticeship-related instructional materials. The final report provides a summary and a narrative account of these project activities: identification of materials; identification of apprenticeship curriculum needs;…

  1. Drilling, Completion, and Data Collection Plans An Assessment of Geological Carbon Sequestration Options in the Illinois Basin: Phase III

    SciTech Connect

    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

  2. San Jose, Costa Rica

    NASA Technical Reports Server (NTRS)

    2007-01-01

    San Jose, capital city of Costa Rica, fills the valley between two steep mountain ranges. In this image made from data collected by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument on NASA's Terra satellite, visible, shortwave, and near-infrared wavelengths of light that the sensor observed have been combined to produce a false-color version of the scene in which vegetation is red, urban areas are silvery gray, water is dark blue, and clouds are white. The image was captured on February 8, 2007. San Jose is in the center of the image. The Rio Torres winds through downtown San Jose. Cartago, the much smaller colonial capital, sits in the lower right corner, while the city of Alajuela appears across the river, northwest of San Jose. The cities' manmade surfaces contrast sharply with the lushly vegetated landscape surrounding the city. Greenhouses are common in the region, and their glass roofs may be the brilliant white spots around the outer edges the cities. The long, straight runway of the Tobias Bolanos International Airport is visible as a dark line southeast of Alajuela. The landscape around the two cities shown here is rugged. Steep mountain peaks cast dark shadows across their leeward slopes. Patches of dark red vegetation on the mountains north of San Jose may be rainforest. Coffee plantations also cover the slopes of the mountains around the city. February is the dry season in Costa Rica. During the rainy season, from about April to November, clouds usually block the satellite's view of this tropical location. NASA image created by Jesse Allen, using data provided courtesy of Asaf Ullah and Tim Gubbels, SERVIR project.

  3. Complete Longitudinal Analyses of the Randomized, Placebo-controlled, Phase III Trial of Sunitinib in Patients with Gastrointestinal Stromal Tumor Following Imatinib Failure

    PubMed Central

    Demetri, George D.; Garrett, Christopher R.; Schöffski, Patrick; Shah, Manisha H.; Verweij, Jaap; Leyvraz, Serge; Hurwitz, Herbert I.; Pousa, Antonio Lopez; Le Cesne, Axel; Goldstein, David; Paz-Ares, Luis; Blay, Jean-Yves; McArthur, Grant A.; Xu, Qiang (Casey); Huang, Xin; Harmon, Charles S.; Tassell, Vanessa; Cohen, Darrel P.; Casali, Paolo G.

    2014-01-01

    Purpose To analyze final long-term survival and clinical outcomes from the randomized phase III study of sunitinib in gastrointestinal stromal tumor (GIST) patients after imatinib failure; to assess correlative angiogenesis biomarkers with patient outcomes. Experimental Design Blinded sunitinib or placebo was given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned patients could cross over to sunitinib at disease progression/study unblinding. Overall survival (OS) was analyzed using conventional statistical methods and the rank-preserving structural failure time (RPSFT) method to explore crossover impact. Circulating levels of angiogenesis biomarkers were analyzed. Results In total, 243 patients were randomized to receive sunitinib and 118 to placebo, 103 of whom crossed over to open-label sunitinib. Conventional statistical analysis showed that OS converged in the sunitinib and placebo arms (median 72.7 versus 64.9 weeks; hazard ratio [HR], 0.876; P = 0.306) as expected, given the crossover design. RPSFT analysis estimated median OS for placebo of 39.0 weeks (HR, 0.505, 95% CI, 0.262–1.134; P = 0.306). No new safety concerns emerged with extended sunitinib treatment. No consistent associations were found between the pharmacodynamics of angiogenesis-related plasma proteins during sunitinib treatment and clinical outcome. Conclusions The crossover design provided evidence of sunitinib clinical benefit based on prolonged time to tumor progression during the double-blind phase of this trial. As expected, following crossover there was no statistical difference in OS. RPSFT analysis modeled the absence of crossover, estimating a substantial sunitinib OS benefit relative to placebo. Long-term sunitinib treatment was tolerated without new adverse events. PMID:22661587

  4. Dolutegravir in Antiretroviral-Experienced Patients With Raltegravir- and/or Elvitegravir-Resistant HIV-1: 24-Week Results of the Phase III VIKING-3 Study

    PubMed Central

    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

  5. A Microfabricated Segmented-Involute-Foil Regenerator for Enhancing Reliability and Performance of Stirling Engines. Phase III Final Report for the Radioisotope Power Conversion Technology NRA

    NASA Technical Reports Server (NTRS)

    Ibrahim, Mounir B.; Gedeon, David; Wood, Gary; McLean, Jeffrey

    2009-01-01

    Under Phase III of NASA Research Announcement contract NAS3-03124, a prototype nickel segmented-involute-foil regenerator was microfabricated and tested in a Sunpower Frequency-Test-Bed (FTB) Stirling convertor. The team for this effort consisted of Cleveland State University, Gedeon Associates, Sunpower Inc. and International Mezzo Technologies. Testing in the FTB convertor produced about the same efficiency as testing with the original random-fiber regenerator. But the high thermal conductivity of the prototype nickel regenerator was responsible for a significant performance degradation. An efficiency improvement (by a 1.04 factor, according to computer predictions) could have been achieved if the regenerator was made from a low-conductivity material. Also, the FTB convertor was not reoptimized to take full advantage of the microfabricated regenerator s low flow resistance; thus, the efficiency would likely have been even higher had the FTB been completely reoptimized. This report discusses the regenerator microfabrication process, testing of the regenerator in the Stirling FTB convertor, and the supporting analysis. Results of the pre-test computational fluid dynamics (CFD) modeling of the effects of the regenerator-test-configuration diffusers (located at each end of the regenerator) are included. The report also includes recommendations for further development of involute-foil regenerators from a higher-temperature material than nickel.

  6. Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

    PubMed Central

    Boer, R H de; Smith, I E; Pastorino, U; O'Brien, M E R; Ramage, F; Ashley, S; Goldstraw, P

    1999-01-01

    Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaign PMID:10188899

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

    PubMed

    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 <30% grade 3-4 non-haematological toxicity. We treated 39 patients (34 AML; five MDS 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.

  8. Comparison of geochemical data obtained using four brine sampling methods at the SECARB Phase III Anthropogenic Test CO2 injection site, Citronelle Oil Field, Alabama

    USGS Publications Warehouse

    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.

  9. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    SciTech Connect

    Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Ishikawa, Hitoshi; Yanagi, Takeshi; Hirasawa, Naoki; Kamada, Tadashi; Mizoe, Jun-Etsu; Kanai, Tatsuaki; Tsujii, Hirohiko; Ohnishi, Yoshitaka

    2007-03-01

    Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.

  10. 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.

    PubMed

    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.

  11. Gefitinib in Combination With Irradiation With or Without Cisplatin in Patients With Inoperable Stage III Non-Small Cell Lung Cancer: A Phase I Trial

    SciTech Connect

    Rothschild, Sacha; Bucher, Stephan E.; Bernier, Jacques; Aebersold, Daniel M.; Zouhair, Aberrahim; Ries, Gerhard; Lombrieser, Norbert; Lippuner, Thomas; Luetolf, Urs M.; Glanzmann, Christoph; Ciernik, I. Frank

    2011-05-01

    Purpose: To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m{sup 2} (Step 2). Gefitinib was maintained for up to 2 years until disease progression or toxicity. Results: Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1-2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions. Conclusions: Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.

  12. Phase I/II trial of whole-abdominal plus pelvic irradiation for Astler-Coller stage beta 2, C colorectal cancer

    SciTech Connect

    Patanaphan, V.; Salazar, O.M.; Slawson, R.G.; Sewchand, W.

    1988-02-01

    From 1982 to 1986, after radical surgery (S) for carcinoma of the rectum and rectosigmoid colon, 25 consecutive patients were entered into a Phase I/II study exploring adjuvant radiation (RT). The latter was given with a single fraction of whole abdomen (mid-body) irradiation (MBI), followed by conventional whole pelvis irradiation (WPI). The minimum follow-up time was 12 months, and the maximum was 44 months. There was escalation of the single MBI dose: 5 Gy in 11 patients, 6 Gy in two patients, and 8 Gy in 10 patients. The 2-year survival rate has been 100 and 45% for Stages B2 and C patients. Only 1/7 Astler-Coller Stage B2 patients failed; this failure was in the lungs. Seven of 15 patients with Stage C failed: one locally, three in the liver, and three in the lungs. Single MBI doses greater than 5 Gy have yielded a high incidence of intestinal obstruction when combined with routine WPI. Consequently, this combination requires both some modification and careful attention if used in future trials exploring new treatment approaches for colorectal cancer.

  13. 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.

    PubMed

    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.

  14. 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

    PubMed Central

    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

  15. A Randomized Controlled Phase III Trial of Recombinant Human Granulocyte Colony-Stimulating Factor (Filgrastim) for Treatment of Severe Chronic Neutropenia

    PubMed Central

    Dale, David C.; Bonilla, Mary Ann; Davis, Mark W.; Nakanishi, Arline M.; Hammond, William P.; Kurtzberg, Joanne; Wang, Winfred; Jakubowski, Ann; Winton, Elliott; Lalezari, Parviz; Robinson, William; Glaspy, John A.; Emerson, Steve; Gabrilove, Janice; Vincent, Martha; Boxer, Laurence A.

    2014-01-01

    Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 × 109/L) due to these diseases were enrolled in this multi-center phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 μg/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of ≥ 1.5 × 109/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently: adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events. PMID:8490166

  16. Improvement in glycated haemoglobin evaluated by baseline body mass index: a meta‐analysis of the liraglutide phase III clinical trial programme

    PubMed Central

    Montanya, E.; Fonseca, V.; Colagiuri, S.; Blonde, L.; Donsmark, M.; Nauck, M. A.

    2016-01-01

    In the liraglutide clinical trial programme, liraglutide 1.2 and 1.8 mg were found to effectively lower glycated haemoglobin (HbA1c) in patients with type 2 diabetes (T2D). It is unknown whether baseline body mass index (BMI) is a predictor of change in HbA1c observed during a clinical trial with liraglutide or placebo treatment. The present meta‐analysis of patient‐level data, using pooled data from seven phase III trials [LEAD‐1–6 and the liraglutide versus sitagliptin trial (LIRA–DPP‐4)] for liraglutide 1.2, 1.8 mg and placebo (n = 3222), identified no significant correlation between baseline BMI (<20 kg/m2 up to 45 kg/m2) and HbA1c reduction for placebo or liraglutide 1.2 mg, and a modest, clinically non‐relevant, association for liraglutide 1.8 mg [−0.010 (95% confidence interval −0.020, −0.001)], whereby a 10 kg/m2 increase in baseline BMI corresponded to 0.10%‐point (1.1 mmol/mol) greater HbA1c reduction. In summary, reductions in HbA1c obtained during clinical trials with liraglutide or placebo treatment were independent of baseline BMI. PMID:26662611

  17. A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

    SciTech Connect

    Hille, Andrea . E-mail: ahille@med.uni-goettingen.de; Schmidberger, Heinz; Hermann, Robert M.; Christiansen, Hans; Saile, Bernhard; Pradier, Olivier; Hess, Clemens F.

    2005-12-01

    Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.

  18. Methylene blue-assisted technique for harvesting lymph nodes after radical surgery for gastric cancer: a prospective randomized phase III study

    PubMed Central

    2014-01-01

    Background This randomized Phase III trial will evaluate whether the methylene blue-assisted technique is efficient for harvesting lymph nodes after radical surgery for gastric cancer. Methods/design Patients that undergo distal or total gastrectomy with radical nodal dissection will be randomly assigned to Group A: the standard group, the lymph nodes (LNs) will be harvested from the fresh specimen immediately after surgery, or Group B: the methylene blue-assisted group, where the LNs will be harvested from specimens fixed with 10% buffered formalin with methylene blue for 48 hours after surgery. The primary endpoint is the ratio of the number of the harvested LNs per time (minute). The secondary endpoint is the number of harvested LNs. A 25% reduction in the ratio of harvested lymph-node/time (minute) was determined to be necessary for this test treatment, considering the balance between the cost and benefit. Retrospective data was used to estimate the ratio of the number of the harvested LNs per time (minute) to be 40/30 minutes in Group A. A 25% risk reduction and a rate of 40/22.5 minutes is expected in Group B. Therefore, the sample size required ensuring a two-sided alpha error of 5% and statistical power of 80% is 52 patients, with 26 patients per arm. The number of patients to be accrued was set at 60 in total, due to the likelihood of enrolling ineligible patients. Trial registration UMIN000008624 PMID:24597931

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

    SciTech Connect

    Eyer, James M.; Erdman, Bill; Iannucci, Joseph J., Jr.

    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.

  20. Improvement in glycated haemoglobin evaluated by baseline body mass index: a meta-analysis of the liraglutide phase III clinical trial programme.

    PubMed

    Montanya, E; Fonseca, V; Colagiuri, S; Blonde, L; Donsmark, M; Nauck, M A

    2016-07-01

    In the liraglutide clinical trial programme, liraglutide 1.2 and 1.8 mg were found to effectively lower glycated haemoglobin (HbA1c) in patients with type 2 diabetes (T2D). It is unknown whether baseline body mass index (BMI) is a predictor of change in HbA1c observed during a clinical trial with liraglutide or placebo treatment. The present meta-analysis of patient-level data, using pooled data from seven phase III trials [LEAD-1-6 and the liraglutide versus sitagliptin trial (LIRA-DPP-4)] for liraglutide 1.2, 1.8 mg and placebo (n = 3222), identified no significant correlation between baseline BMI (<20 kg/m(2) up to 45 kg/m(2) ) and HbA1c reduction for placebo or liraglutide 1.2 mg, and a modest, clinically non-relevant, association for liraglutide 1.8 mg [-0.010 (95% confidence interval -0.020, -0.001)], whereby a 10 kg/m(2) increase in baseline BMI corresponded to 0.10%-point (1.1 mmol/mol) greater HbA1c reduction. In summary, reductions in HbA1c obtained during clinical trials with liraglutide or placebo treatment were independent of baseline BMI. PMID:26662611

  1. International Phase III Trial Assessing Neoadjuvant Cisplatin, Methotrexate, and Vinblastine Chemotherapy for Muscle-Invasive Bladder Cancer: Long-Term Results of the BA06 30894 Trial

    PubMed Central

    2011-01-01

    Purpose This article presents the long-term results of the international multicenter randomized trial that investigated the use of neoadjuvant cisplatin, methotrexate, and vinblastine (CMV) chemotherapy in patients with muscle-invasive urothelial cancer of the bladder treated by cystectomy and/or radiotherapy. Nine hundred seventy-six patients were recruited between 1989 and 1995, and median follow-up is now 8.0 years. Patients and Methods This was a randomized phase III trial of either no neoadjuvant chemotherapy or three cycles of CMV. Results The previously reported possible survival advantage of CMV is now statistically significant at the 5% level. Results show a statistically significant 16% reduction in the risk of death (hazard ratio, 0.84; 95% CI, 0.72 to 0.99; P = .037, corresponding to an increase in 10-year survival from 30% to 36%) after CMV. Conclusion We conclude that CMV chemotherapy improves outcome as first-line adjunctive treatment for invasive bladder cancer. Two large randomized trials (by the Medical Research Council/European Organisation for Research and Treatment of Cancer and Southwest Oncology Group) have confirmed a statistically significant and clinically relevant survival benefit, and neoadjuvant chemotherapy followed by definitive local therapy should be viewed as state of the art, as compared with cystectomy or radiotherapy alone, for deeply invasive bladder cancer. PMID:21502557

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

    PubMed

    Farrokhi, Shokrollah; Gheybi, Mohammad Kazzem; Movahhed, Ali; Dehdari, Reyhaneh; Gooya, Mostafa; Keshvari, Saman; Gholampour, Hossein; Mansourian, Zohreh; Khosravi, Yasaman; Ghahramani, Forough; Zandi, Sahar; Etemadan, Razieh; Tahmasebi, Rahim; Reaisi, Alireza; Keshmiri, Saeed; Fadaizadeh, Lida; Masjedi, Mohammad Reza

    2014-10-01

    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. PMID:25150076

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

    PubMed Central

    Pugliese, Mariateresa; Gallo, Marco; Brignardello, Enrico; Milla, Paola; Orlandi, Fabio; Limone, Paolo Piero; Arvat, Emanuela; Boccuzzi, Giuseppe; Piovesan, Alessandro

    2016-01-01

    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. PMID:27766105

  4. Assessing the impact of safety monitoring on the efficacy analysis in large Phase III group sequential trials with non-trivial safety event rate.

    PubMed

    Weng, Yanqiu; Palesch, Yuko Y; DeSantis, Stacia M; Zhao, Wenle

    2016-01-01

    In Phase III clinical trials for life-threatening conditions, some serious but expected adverse events, such as early deaths or congestive heart failure, are often treated as the secondary or co-primary endpoint, and are closely monitored by the Data and Safety Monitoring Committee (DSMC). A naïve group sequential design (GSD) for such a study is to specify univariate statistical boundaries for the efficacy and safety endpoints separately, and then implement the two boundaries during the study, even though the two endpoints are typically correlated. One problem with this naïve design, which has been noted in the statistical literature, is the potential loss of power. In this article, we develop an analytical tool to evaluate this negative impact for trials with non-trivial safety event rates, particularly when the safety monitoring is informal. Using a bivariate binary power function for the GSD with a random-effect component to account for subjective decision-making in safety monitoring, we demonstrate how, under common conditions, the power loss in the naïve design can be substantial. This tool may be helpful to entities such as the DSMCs when they wish to deviate from the prespecified stopping boundaries based on safety measures. PMID:26010228

  5. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.

    PubMed

    Coronel, Jaime; Cetina, Lucely; Pacheco, Irlanda; Trejo-Becerril, Catalina; González-Fierro, Aurora; de la Cruz-Hernandez, Erick; Perez-Cardenas, Enrique; Taja-Chayeb, Lucia; Arias-Bofill, Daymi; Candelaria, Myrna; Vidal, Silvia; Dueñas-González, Alfonso

    2011-12-01

    The reversing of epigenetic aberrations using the inhibitors of DNA methylation and histone deacetylases may have therapeutic value in cervical cancer. This is a randomized phase III, placebo-controlled study of hydralazine and valproate (HV) added to cisplatin topotecan in advanced cervical cancer. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression. Response, toxicity, and PFS were evaluated, and 36 patients (17 CT + HV and 19 CT + PLA) were included. The median number of cycles was 6. There were four PRs to CT + HV and one in CT + PLA. Stable disease in five (29%) and six (32%) patients, respectively, whereas eight (47%) and 12 (63%) showed progression (P = 0.27). At a median follow-up time of 7 months (1-22), the median PFS is 6 months for CT + PLA and 10 months for CT + HV (P = 0.0384, two tailed). Although preliminary, this study represents the first randomized clinical trial to demonstrate a significant advantage in progression-free survival for epigenetic therapy over one of the current standard combination chemotherapy in cervical cancer. Molecular correlates with response and survival from this trial are pending to analyze.

  6. Educacion Fisica in Costa Rica.

    ERIC Educational Resources Information Center

    Cleland, Donna

    1980-01-01

    The goal of Costa Rica's Department of Physical Education and Sports is the "utilization of sport, physical education, and recreation as instruments of socialization and contribution to the improved health of Costa Ricans." (JN)

  7. Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer

    PubMed Central

    Bazarbashi, Shouki; Aljubran, Ali; Alzahrani, Ahmad; Mohieldin, Ahmed; Soudy, Hussein; Shoukri, Mohammed

    2015-01-01

    Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m2. Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity. PMID:26207614

  8. Binding of HgII to high-affinity sites on bacteria inhibits reduction to Hg0 by mixed FeII/III phases.

    PubMed

    Mishra, Bhoopesh; O'Loughlin, Edward J; Boyanov, Maxim I; Kemner, Kenneth M

    2011-11-15

    Magnetite and green rust have been shown to reduce aqueous Hg(II) to Hg(0). In this study, we tested the ability of magnetite and green rust to reduce Hg(II) sorbed to 2 g · L(-1) of biomass (Bacillus subtilis), at high (50 μM) and low (5 μM) Hg loadings and at pH 6.5 and 5.0. At high Hg:biomass loading, where Hg(II) binding to biomass is predominantly through carboxyl functional groups, Hg L(III)-edge X-ray absorption spectroscopy showed reduction of Hg(II) to Hg(0) by magnetite. Reduction occurred within 2 h and 2 d at pH 6.5 and 5.0, respectively. At low Hg:biomass loading, where Hg(II) binds to biomass via sulfhydryl functional groups, Hg(II) was not reduced by magnetite at pH 6.5 or 5.0 after 2 months of reaction. Green rust, which is generally a stronger reductant than magnetite, reduced about 20% of the total Hg(II) bound to biomass via sulfhydryl groups to Hg(0) in 2 d. These results suggest that Hg(II) binding to carboxyl groups does not significantly inhibit the reduction of Hg(II) by magnetite. However, the binding of Hg(II) to biomass via sulfhydryl groups severely inhibits the ability of mixed Fe(II/III) phases like magnetite and green rust to reduce Hg(II) to Hg(0). The mobility of heavy metal contaminants in aquatic and terrestrial environments is greatly influenced by their speciation, especially their oxidation state. In the case of Hg, reduction of Hg(II) to Hg(0) can increase Hg mobility because of the volatility of Hg(0). Since Hg is typically present in aquatic and terrestrial systems at low concentrations, binding of Hg(II) to high-affinity sites on bacteria could have important implications for the potential reduction of Hg(II) to Hg(0) and the overall mobility of Hg in biostimulated subsurface environments. PMID:21913727

  9. Binding of HgII to high-affinity sites on bacteria inhibits reduction to Hg0 by mixed FeII/III phases.

    PubMed

    Mishra, Bhoopesh; O'Loughlin, Edward J; Boyanov, Maxim I; Kemner, Kenneth M

    2011-11-15

    Magnetite and green rust have been shown to reduce aqueous Hg(II) to Hg(0). In this study, we tested the ability of magnetite and green rust to reduce Hg(II) sorbed to 2 g · L(-1) of biomass (Bacillus subtilis), at high (50 μM) and low (5 μM) Hg loadings and at pH 6.5 and 5.0. At high Hg:biomass loading, where Hg(II) binding to biomass is predominantly through carboxyl functional groups, Hg L(III)-edge X-ray absorption spectroscopy showed reduction of Hg(II) to Hg(0) by magnetite. Reduction occurred within 2 h and 2 d at pH 6.5 and 5.0, respectively. At low Hg:biomass loading, where Hg(II) binds to biomass via sulfhydryl functional groups, Hg(II) was not reduced by magnetite at pH 6.5 or 5.0 after 2 months of reaction. Green rust, which is generally a stronger reductant than magnetite, reduced about 20% of the total Hg(II) bound to biomass via sulfhydryl groups to Hg(0) in 2 d. These results suggest that Hg(II) binding to carboxyl groups does not significantly inhibit the reduction of Hg(II) by magnetite. However, the binding of Hg(II) to biomass via sulfhydryl groups severely inhibits the ability of mixed Fe(II/III) phases like magnetite and green rust to reduce Hg(II) to Hg(0). The mobility of heavy metal contaminants in aquatic and terrestrial environments is greatly influenced by their speciation, especially their oxidation state. In the case of Hg, reduction of Hg(II) to Hg(0) can increase Hg mobility because of the volatility of Hg(0). Since Hg is typically present in aquatic and terrestrial systems at low concentrations, binding of Hg(II) to high-affinity sites on bacteria could have important implications for the potential reduction of Hg(II) to Hg(0) and the overall mobility of Hg in biostimulated subsurface environments.

  10. SAGE III

    Atmospheric Science Data Center

    2016-06-15

    SAGE III Data and Information The Stratospheric Aerosol and Gas ... on the spacecraft. SAGE III produced L1 and L2 scientific data from 5/07/2002 until 12/31/2005. The flight of the second instrument is as ... Guide Documents:  Project Guide Data Products User's Guide  (PDF) Relevant Documents:  ...

  11. High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial

    PubMed Central

    Hoffer, L. John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H.

    2015-01-01

    Background 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. Methods and Findings 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. Conclusions 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

  12. A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee.

    PubMed

    Spierings, Egilius L H; Fidelholtz, James; Wolfram, Gernot; Smith, Michael D; Brown, Mark T; West, Christine R

    2013-09-01

    Tanezumab is a humanized monoclonal antinerve growth factor antibody in development for treatment of chronic pain. In a phase III, placebo- and active-controlled study, we investigated the efficacy and safety of tanezumab for osteoarthritis (OA) hip or knee pain. Patients (N=610) received up to 2 doses of intravenous tanezumab (5 or 10mg in 8-week intervals), controlled-release oral oxycodone (10 to 40 mg every 12 hours), or placebo. The primary endpoint was mean change from baseline to week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain score for tanezumab versus placebo and oxycodone. Secondary endpoints included change from baseline in WOMAC Physical Function and Stiffness scores, Patient's Global Assessment (PGA) of OA, and patient response, defined as ≥ 30%, ≥ 50%, ≥ 70%, and ≥ 90% improvement from baseline in WOMAC Pain score. Tolerability and safety also were assessed. Both tanezumab groups demonstrated significant improvements in WOMAC Pain score versus placebo (P<.001) and oxycodone (P ≤.018). Tanezumab also provided significant improvements versus placebo and oxycodone for WOMAC Physical Function and Stiffness scores and PGA of OA (P ≤.002 for all) at week 8. For all analyses, oxycodone did not differ from placebo. Adverse event frequency was higher with oxycodone (63.3%) than tanezumab (40.7% to 44.7%) or placebo (35.5%); serious adverse event frequency was similar among treatments. The adverse event profile for tanezumab was similar to previous tanezumab studies. Results indicate that tanezumab is efficacious in the treatment of OA pain; no new safety signals were identified.

  13. Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia

    PubMed Central

    Konopleva, Marina; Thall, Peter F.; Yi, Cecilia Arana; Borthakur, Gautam; Coveler, Andrew; Bueso-Ramos, Carlos; Benito, Juliana; Konoplev, Sergej; Gu, Yongchuan; Ravandi, Farhad; Jabbour, Elias; Faderl, Stefan; Thomas, Deborah; Cortes, Jorge; Kadia, Tapan; Kornblau, Steven; Daver, Naval; Pemmaraju, Naveen; Nguyen, Hoang Q.; Feliu, Jennie; Lu, Hongbo; Wei, Caimiao; Wilson, William R.; Melink, Teresa J.; Gutheil, John C.; Andreeff, Michael; Estey, Elihu H.; Kantarjian, Hagop

    2015-01-01

    We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided a rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and hydroxyl-amine nitrogen mustards that induce DNA cross-linking in hypoxic cells under low oxygen concentrations. In this phase I/II study, patients with relapsed/refractory acute myeloid leukemia (n=40) after 1 or 2 prior treatments or acute lymphoblastic leukemia (n=10) after any number of prior treatments received PR104; dose ranged from 1.1 to 4 g/m2. The most common treatment-related grade 3/4 adverse events were myelosuppression (anemia 62%, neutropenia 50%, thrombocytopenia 46%), febrile neutropenia (40%), infection (24%), and enterocolitis (14%). Ten of 31 patients with acute myeloid leukemia (32%) and 2 of 10 patients with acute lymphoblastic leukemia (20%) who received 3 g/m2 or 4 g/m2 had a response (complete response, n=1; complete response without platelet recovery, n=5; morphological leukemia-free state, n=6). The extent of hypoxia was evaluated by the hypoxia tracer pimonidazole administered prior to a bone marrow biopsy and by immunohistochemical assessments of hypoxia-inducible factor alpha and carbonic anhydrase IX. A high fraction of leukemic cells expressed these markers, and PR104 administration resulted in measurable decrease of the proportions of hypoxic cells. These findings indicate that hypoxia is a prevalent feature of the leukemic microenvironment and that targeting hypoxia with hypoxia-activated prodrugs warrants further evaluation in acute leukemia. The trial is registered at clinicaltrials.gov identifier: 01037556. PMID:25682597

  14. Silver Clear Nylon Dressing is Effective in Preventing Radiation-Induced Dermatitis in Patients With Lower Gastrointestinal Cancer: Results From a Phase III Study

    SciTech Connect

    Niazi, Tamim M.; Vuong, Te; Azoulay, Laurant; Marijnen, Corrie; Bujko, Kryzstof; Nasr, Elie; Lambert, Christine; Duclos, Marie; Faria, Sergio; David, Marc; Cummings, Bernard

    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.

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

    PubMed Central

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

    2011-01-01

    Purpose Pooled results from 2 randomized, placebo-controlled, US phase III studies (NCT00224107, NCT00224120) showed that silodosin, a uroselective α-blocker, significantly improved International Prostate Symptom Scores (IPSS) in men with symptomatic benign prostatic hyperplasia (BPH). This analysis evaluated the effect of silodosin on each symptom assessed by IPSS questionnaire. Materials and methods Study participants (N = 923) were men aged ≥50 years with IPSS ≥13 and Qmax 4–15 mL/s. They received silodosin 8 mg or placebo once daily for 12 weeks. Patient responses to 7 IPSS questions were collected at weeks 0 (baseline), 0.5, 1, 2, 4, and 12 and scored on a 6-point scale. Efficacy of silodosin versus placebo was assessed by analysis of covariance. Results For each symptom, the 2 treatment groups had similar mean baseline scores. Decrease in score from baseline (mean ± standard deviation) to last observation was significantly greater with silodosin than with placebo for all symptoms (P < 0.005); symptom improvement with silodosin (versus placebo) was greatest for weak stream (silodosin, −1.1 ± 1.4 versus placebo, −0.5 ± 1.2; P < 0.0001) and smallest for nocturia (silodosin, −0.6 ± 1.1 versus placebo, −0.4 ± 1.2; P = 0.0037). Compared with placebo, silodosin significantly improved nocturia within 1 week (silodosin, −0.5 ± 1.07 versus placebo, −0.3 ± 1.05; P = 0.009) and all other symptoms within 3 to 4 days (P < 0.01). Conclusions Silodosin significantly improved all BPH-associated symptoms assessed by IPSS questionnaire within the first week of treatment. All improvements were maintained over the 12-week study period. PMID:24198629

  16. 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

    SciTech Connect

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

    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.

  17. Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.

    PubMed

    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.

  18. FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

    PubMed Central

    2009-01-01

    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 PMID:19807917

  19. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis.

    PubMed

    Vannucchi, Alessandro M; Kantarjian, Hagop M; Kiladjian, Jean-Jacques; Gotlib, Jason; Cervantes, Francisco; Mesa, Ruben A; Sarlis, Nicholas J; Peng, Wei; Sandor, Victor; Gopalakrishna, Prashanth; Hmissi, Abdel; Stalbovskaya, Viktoriya; Gupta, Vikas; Harrison, Claire; Verstovsek, Srdan

    2015-09-01

    Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms. Overall, 301 patients received ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 patients received placebo (n=154) or best available therapy (n=73). After a median three years of follow up, intent-to-treat analysis showed that patients who received ruxolitinib had prolonged survival compared with patients who received placebo or best available therapy [hazard ratio=0.65; 95% confidence interval (95%CI): 0.46-0.90; P=0.01]; the crossover-corrected hazard ratio was 0.29 (95%CI: 0.13-0.63). Both patients with intermediate-2- or high-risk disease showed prolonged survival, and patients with high-risk disease in the ruxolitinib group had survival similar to that of patients with intermediate-2-risk disease in the control group. The Kaplan-Meier estimate of overall survival at week 144 was 78% in the ruxolitinib arm, 61% in the intent-to-treat control arm, and 31% in the crossover-adjusted control arm. While larger spleen size at baseline was prognostic for shortened survival, reductions in spleen size with ruxolitinib treatment correlated with longer survival. These findings are consistent with previous reports and support that ruxolitinib offers a survival benefit for patients with myelofibrosis compared with conventional therapies. (clinicaltrials.gov identifiers: COMFORT-I, NCT00952289; COMFORT-II, NCT00934544).

  20. Continuous 7-Days-A-Week External Beam Irradiation in Locally Advanced Cervical Cancer: Final Results of the Phase I/II Study

    SciTech Connect

    Serkies, Krystyna; Dziadziuszko, Rafal; Jassem, Jacek

    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

  1. Phase I Study of Oxaliplatin in Combination With Capecitabine and Radiotherapy as Postoperative Treatment for Stage II and III Rectal Cancer

    SciTech Connect

    Jin Jing

    2008-11-01

    Purpose: A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin (OXA) combined with capecitabine and radiotherapy as adjuvant treatment in patients with operable rectal cancer. Patients and Methods: A total of 21 patients with Stage II or III rectal adenocarcinoma after curative surgery were treated with radiotherapy to a total dose of 50 Gy in 5 weeks. OXA was administered at a dosage of 40 (n = 6), 50 (n = 3),60 (n = 3), 70 (n = 3), or 80 mg/m{sup 2} (n = 6) once a week for 2 weeks (first cycle) followed by a second cycle after a 7-day break. Capecitabine at a fixed dose of 1,300 mg/m{sup 2}/d was administered orally at the same schedule as for OXA. DLT was defined as Grade 3 or 4 hematologic and nonhematologic toxicity. Results: Grade 1-3 leukopenia, diarrhea, and nausea/vomiting were the most common toxic side effects, and most were Grade 1-2. A DLT was first observed in 1 of 3 patients at 40 mg/m{sup 2} (Grade 3 diarrhea) but was not observed in the next 3 patients at the same level or in patients who received a dose level of 50-70 mg/m{sup 2}. At 80 mg/m{sup 2}, DLT occurred in 3 of 6 patients (1 Grade 4 leukopenia and 2 Grade 3 diarrhea). Conclusions: OXA combined with a fixed dose of capecitabine at 625 mg/m{sup 2} twice daily by mouth plus radiotherapy in the adjuvant setting was tolerable and clinically feasible. The maximal tolerated dose of OXA in this setting was 80 mg/m{sup 2}, comparable to the maximal tolerated dose of OXA in the neoadjuvant setting.

  2. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial

    PubMed Central

    von Mehren, Margaret; Jones, Robin L.; Hensley, Martee L.; Schuetze, Scott M.; Staddon, Arthur; Milhem, Mohammed; Elias, Anthony; Ganjoo, Kristen; Tawbi, Hussein; Van Tine, Brian A.; Spira, Alexander; Dean, Andrew; Khokhar, Nushmia Z.; Park, Youn Choi; Knoblauch, Roland E.; Parekh, Trilok V.; Maki, Robert G.; Patel, Shreyaskumar R.

    2016-01-01

    Purpose This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. Patients and Methods Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control—progression-free survival (PFS), time to progression, objective response rate, and duration of response—as well as safety and patient-reported symptom scoring. Results A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm. Conclusion Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies. PMID:26371143

  3. 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

    PubMed Central

    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

  4. 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

    PubMed Central

    Lee, Ching-Tzu; Jeng, Cherng-Jye; Yeh, Lian-Shung; Yen, Ming-Shyen; Chen, Shih-Ming; Lee, Chyi-Long; Lin, Willie; Hsu, Chun-Sen

    2016-01-01

    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. PMID:27343206

  5. Semicontinuous Low-Dose-Rate Teletherapy for the Treatment of Recurrent Glial Brain Tumors: Final Report of a Phase I/II Study

    SciTech Connect

    Siker, Malika L.; Firat, Selim Y.; Mueller, Wade; Krouwer, Hendrikus; Schultz, Christopher J.

    2012-02-01

    Purpose: Semicontinuous low-dose-rate teletherapy (SLDR) is a novel irradiation strategy that exploits the increased radiosensitivity of glial cells in a narrow range of reduced dose rate. We present the final report of a prospective Phase I/II study testing the feasibility of SLDR for the treatment of recurrent gliomas. Methods and Materials: Patients with previously irradiated recurrent gliomas were enrolled from November 1993 to March 1998. Patients received SLDR, delivered 6 to 8 hours/day at a dose rate of 40 to 50 cGy/hour for a total dose of 30 to 35 Gy given over 12 days using a modified cobalt-60 treatment unit. Acute central nervous system toxicity after SLDR treatment was the primary endpoint. Overall survival was a secondary endpoint. Results: Twenty patients were enrolled (14 World Health Organization Grade 4 glioma, 5 Grade 2 glioma, 1 ependymoma). No patients developed {>=}Grade 3 central nervous system toxicity at 3 months without radiographic evidence of tumor progression. Overall survival after SLDR was 56% at 6 months, 28% at 12 months, and 17% at 24 months. One patient survived >48 months, and 1 patient survived >60 months after SLDR treatment. Re-resection before SLDR treatment significantly improved 1-year overall survival for all patients and patients with Grade 4 glioma. Conclusion: The delivery of SLDR is feasible in patients with recurrent gliomas and resulted in improved outcomes for patients who underwent re-resection. There were 2 long-term survivors (>48 months). This pilot study supports the notion that reduced dose rate influences the efficacy and tolerance of reirradiation in the treatment of recurrent gliomas.

  6. 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.

    PubMed

    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. PMID:27265743

  7. Deterioration in quality of life (QoL) in patients with malignant ascites: results from a phase II/III study comparing paracentesis plus catumaxomab with paracentesis alone

    PubMed Central

    Wimberger, P.; Gilet, H.; Gonschior, A-K.; Heiss, M. M.; Moehler, M.; Oskay-Oezcelik, G.; Al-Batran, S-E.; Schmalfeldt, B.; Schmittel, A.; Schulze, E.; Parsons, S. L.

    2012-01-01

    Background Malignant ascites (MA) is associated with poor prognosis and limited palliative therapeutic options. Therefore, quality of life (QoL) assessment is of particular importance to demonstrate new treatment value. Following the demonstration of the superiority of catumaxomab and paracentesis over paracentesis on puncture-free survival, this analysis aimed at comparing deterioration in QoL between both the treatment options. Patients and methods In a randomised, multicentre, phase II/III study of patients with MA due to epithelial cell adhesion molecule (EpCAM) positive cancer, the QoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items (EORTC QLQ-C30) questionnaire at screening, 1, 3 and 7 months after treatment and in the case of re-puncture on the day of paracentesis. Time to first deterioration in QoL was defined as a decrease in the QoL score of at least five points and compared between the catumaxomab (n = 160) and control (n = 85) groups using the log-rank test and Cox proportional hazards models adjusted for baseline score, country and primary tumour type. Results Deterioration in QoL scores appeared more rapidly in the control than in the catumaxomab group (median 19–26 days versus 47–49 days). The difference in time to deterioration in QoL between the groups was statistically significant for all scores (P < 0.01). The hazard ratios ranged from 0.08 to 0.24 (P < 0.01). Conclusions Treatment with catumaxomab delayed deterioration in QoL in patients with MA. Compared with paracentesis alone, catumaxomab enabled patients to benefit from better QoL for a prolonged survival period. PMID:22734013

  8. Deep sequencing analysis of HIV-1 reverse transcriptase at baseline and time of failure in patients receiving rilpivirine in the phase III studies ECHO and THRIVE.

    PubMed

    Van Eygen, Veerle; Thys, Kim; Van Hove, Carl; Rimsky, Laurence T; De Meyer, Sandra; Aerssens, Jeroen; Picchio, Gaston; Vingerhoets, Johan

    2016-05-01

    Minority variants (1.0-25.0%) were evaluated by deep sequencing (DS) at baseline and virological failure (VF) in a selection of antiretroviral treatment-naïve, HIV-1-infected patients from the rilpivirine ECHO/THRIVE phase III studies. Linkage between frequently emerging resistance-associated mutations (RAMs) was determined. DS (llIumina®) and population sequencing (PS) results were available at baseline for 47 VFs and time of failure for 48 VFs; and at baseline for 49 responders matched for baseline characteristics. Minority mutations were accurately detected at frequencies down to 1.2% of the HIV-1 quasispecies. No baseline minority rilpivirine RAMs were detected in VFs; one responder carried 1.9% F227C. Baseline minority mutations associated with resistance to other non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 8/47 VFs (17.0%) and 7/49 responders (14.3%). Baseline minority nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) RAMs M184V and L210W were each detected in one VF (none in responders). At failure, two patients without NNRTI RAMs by PS carried minority rilpivirine RAMs K101E and/or E138K; and five additional patients carried other minority NNRTI RAMs V90I, V106I, V179I, V189I, and Y188H. Overall at failure, minority NNRTI RAMs and NRTI RAMs were found in 29/48 (60.4%) and 16/48 VFs (33.3%), respectively. Linkage analysis showed that E138K and K101E were usually not observed on the same viral genome. In conclusion, baseline minority rilpivirine RAMs and other NNRTI/NRTI RAMs were uncommon in the rilpivirine arm of the ECHO and THRIVE studies. DS at failure showed emerging NNRTI resistant minority variants in seven rilpivirine VFs who had no detectable NNRTI RAMs by PS. PMID:26412111

  9. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial.

    PubMed

    Douillard, Jean-Yves; Shepherd, Frances A; Hirsh, Vera; Mok, Tony; Socinski, Mark A; Gervais, Radj; Liao, Mei-Lin; Bischoff, Helge; Reck, Martin; Sellers, Mark V; Watkins, Claire L; Speake, Georgina; Armour, Alison A; Kim, Edward S

    2010-02-10

    PURPOSE In the phase III INTEREST trial, 1,466 pretreated patients with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or docetaxel. As a preplanned analysis, we prospectively analyzed available tumor biopsies to investigate the relationship between biomarkers and clinical outcomes. METHODS Biomarkers included epidermal growth factor receptor (EGFR) copy number by fluorescent in situ hybridization (374 assessable samples), EGFR protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS (n = 275) mutations. Results For all biomarker subgroups analyzed, survival was similar for gefitinib and docetaxel, with no statistically significant differences between treatments and no significant treatment by biomarker status interaction tests. EGFR mutation-positive patients had longer progression-free survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and higher objective response rate (ORR; 42.1% v 21.1%; P = .04), and patients with high EGFR copy number had higher ORR (13.0% v 7.4%; P = .04) with gefitinib versus docetaxel. CONCLUSION These biomarkers do not appear to be predictive factors for differential survival between gefitinib and docetaxel in this setting of previously treated patients; however, subsequent treatments may have influenced the survival results. For secondary end points of PFS and ORR, some advantages for gefitinib over docetaxel were seen in EGFR mutation-positive and high EGFR copy number patients. There was no statistically significant difference between gefitinib and docetaxel in biomarker-negative patients. This suggests gefitinib can provide similar overall survival to docetaxel in patients across a broad range of clinical subgroups and that EGFR biomarkers such as mutation status may additionally identify which patients are likely to gain greatest PFS and ORR benefit from gefitinib.

  10. Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial

    PubMed Central

    Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

    2015-01-01

    A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8–67.2), 53.4% (95% CI: 48.1–58.7), and 54.9% (95% CI: 48.1–60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6–97.3), 93.8% (95% CI: 91.2–96.4), and 95.3% (95% CI: 93.0–97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective. PMID:25875868

  11. Japanese POEMS syndrome with Thalidomide (J-POST) Trial: study protocol for a phase II/III multicentre, randomised, double-blind, placebo-controlled trial

    PubMed Central

    Katayama, Kanako; Misawa, Sonoko; Sato, Yasunori; Sobue, Gen; Yabe, Ichiro; Watanabe, Osamu; Nishizawa, Masatoyo; Kusunoki, Susumu; Kikuchi, Seiji; Nakashima, Ichiro; Ikeda, Shu-ichi; Kohara, Nobuo; Kanda, Takashi; Kira, Jun-ichi; Hanaoka, Hideki; Kuwabara, Satoshi

    2015-01-01

    Introduction Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a fatal systemic disorder associated with plasma cell dyscrasia and the overproduction of the vascular endothelial growth factor (VEGF). Recently, the prognosis of POEMS was substantially improved by introduction of therapeutic intervention for myeloma. However, no randomised clinical trial has been performed because of the rarity and severity of the disease. Methods and analysis The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome, with an additional 48-week open-label safety study. Adults with POEMS syndrome who have no indication for transplantation are assessed for eligibility at 12 tertiary neurology centres in Japan. Patients who satisfy the eligibility criteria are randomised (1:1) to receive thalidomide (100–300 mg daily) plus dexamethasone (12 mg/m2 on days 1–4 of a 28-day cycle) or placebo plus dexamethasone. Both treatments were administered for 24 weeks (six cycles; randomised comparative study period). Patients who complete the randomised study period or show subacute deterioration during the randomised period participate in the subsequent 48-week open-label safety study (long-term safety period). The primary end point of the study is the reduction rate of serum VEGF levels at 24 weeks. Ethics and dissemination The protocol was approved by the Institutional Review Board of each hospital. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, Japan (No. 22-1716). The J-POST Trial is currently ongoing and is due to finish in August 2015. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations and will also be disseminated to participants. Trial registration number

  12. 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

    PubMed Central

    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

  13. Revisiting dosing regimen using PK/PD modeling: the MODEL1 phase I/II trial of docetaxel plus epirubicin in metastatic breast cancer patients.

    PubMed

    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.

  14. Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

    PubMed

    Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

    2015-01-01

    A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.

  15. Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: A phase I-II study

    SciTech Connect

    Amichetti, M.; Graiff, C.; Fellin, G.; Pani, G.; Bolner, A.; Maluta, S. ); Valdagni, R. Istituto per la Ricerca Scientifica e Tecnologica, Trento )

    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.

  16. Effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib-melphalan-prednisone in the phase III VISTA study.

    PubMed

    Mateos, María Victoria; Richardson, Paul G; Dimopoulos, Meletios A; Palumbo, Antonio; Anderson, Kenneth C; Shi, Hongliang; Elliott, Jennifer; Dow, Edward; van de Velde, Helgi; Niculescu, Liviu; San Miguel, Jesús F

    2015-04-01

    This analysis, using data from the bortezomib-melphalan-prednisone (VMP) arm of the Phase III VISTA study, investigated whether increased cumulative bortezomib dose could improve overall survival (OS) in transplant-ineligible patients with previously untreated multiple myeloma. Median cumulative bortezomib dose received by the 340 patients was 39 mg/m(2); this was selected as the cut-off for defining the dose groups to be compared for OS. Patient characteristics were well balanced between dose groups except for age. OS was significantly longer in the higher (≥39 mg/m(2)) versus lower (<39 mg/m(2)) cumulative bortezomib dose group (median 66.3 vs. 46.2 months; hazard ratio (HR) 0.533, P < 0.0001; age-adjusted HR 0.561, P = 0.0002). To overcome confounding effects of early discontinuations/deaths, which were more common in the lower cumulative dose group (27 vs. 4% of patients discontinued due to adverse events (AEs) in the lower and higher cumulative dose groups, respectively), a landmark analysis was conducted at 180 days, eliminating patients who died or discontinued before this time from the analysis. OS from this landmark remained significantly longer in the higher dose group (median 60.4 vs. 50.3 months; HR 0.709, P = 0.0372). Thus, higher cumulative bortezomib dose, reflecting prolonged treatment duration and/or dose intensity, appears associated with improved OS. Approaches to achieve higher cumulative doses could include subcutaneous bortezomib administration, dose/schedule modifications, continuing therapy in responding patients, and proactive AE management.

  17. 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.

    PubMed

    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.

  18. The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120.

    PubMed

    Karasavvas, Nicos; Billings, Erik; Rao, Mangala; Williams, Constance; Zolla-Pazner, Susan; Bailer, Robert T; Koup, Richard A; Madnote, Sirinan; Arworn, Duangnapa; Shen, Xiaoying; Tomaras, Georgia D; Currier, Jeffrey R; Jiang, Mike; Magaret, Craig; Andrews, Charla; Gottardo, Raphael; Gilbert, Peter; Cardozo, Timothy J; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Paris, Robert; Greene, Kelli; Gao, Hongmei; Gurunathan, Sanjay; Tartaglia, Jim; Sinangil, Faruk; Korber, Bette T; Montefiori, David C; Mascola, John R; Robb, Merlin L; Haynes, Barton F; Ngauy, Viseth; Michael, Nelson L; Kim, Jerome H; de Souza, Mark S

    2012-11-01

    The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200-3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100-200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169-184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100-800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p=0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100-3200) and 3570 (range: 200-12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition.

  19. The Thai phase III trial (RV144) vaccine regimen induces T cell responses that preferentially target epitopes within the V2 region of HIV-1 envelope.

    PubMed

    de Souza, Mark S; Ratto-Kim, Silvia; Chuenarom, Weerawan; Schuetz, Alexandra; Chantakulkij, Somsak; Nuntapinit, Bessara; Valencia-Micolta, Anais; Thelian, Doris; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Paris, Robert M; Kaewkungwal, Jaranit; Michael, Nelson L; Rerks-Ngarm, Supachai; Mathieson, Bonnie; Marovich, Mary; Currier, Jeffrey R; Kim, Jerome H

    2012-05-15

    The Thai HIV phase III prime/boost vaccine trial (RV144) using ALVAC-HIV (vCP1521) and AIDSVAX B/E was, to our knowledge, the first to demonstrate acquisition efficacy. Vaccine-induced, cell-mediated immune responses were assessed. T cell epitope mapping studies using IFN-γ ELISPOT was performed on PBMCs from HIV-1-uninfected vaccine (n = 61) and placebo (n = 10) recipients using HIV-1 Env peptides. Positive responses were measured in 25 (41%) vaccinees and were predominantly CD4(+) T cell-mediated. Responses were targeted within the HIV Env region, with 15 of 25 (60%) of vaccinees recognizing peptides derived from the V2 region of HIV-1 Env, which includes the α(4)β(7) integrin binding site. Intracellular cytokine staining confirmed that Env responses predominated (19 of 30; 63% of vaccine recipients) and were mediated by polyfunctional effector memory CD4(+) T cells, with the majority of responders producing both IL-2 and IFN-γ (12 of 19; 63%). HIV Env Ab titers were higher in subjects with IL-2 compared with those without IL-2-secreting HIV Env-specific effector memory T cells. Proliferation assays revealed that HIV Ag-specific T cells were CD4(+), with the majority (80%) expressing CD107a. HIV-specific T cell lines obtained from vaccine recipients confirmed V2 specificity, polyfunctionality, and functional cytolytic capacity. Although the RV144 T cell responses were modest in frequency compared with humoral immune responses, the CD4(+) T cell response was directed to HIV-1 Env and more particularly the V2 region.

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

    PubMed Central

    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

  1. The Thai Phase III Trial (RV144) Vaccine Regimen Induces T Cell Responses that Preferentially Target Epitopes within the V2 Region of HIV-1 Envelope

    PubMed Central

    de Souza, Mark S.; Ratto-Kim, Silvia; Chuenarom, Weerawan; Schuetz, Alexandra; Chantakulkij, Somsak; Nuntapinit, Bessara; Valencia-Micolta, Anais; Thelian, Doris; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Paris, Robert M.; Kaewkungwal, Jaranit; Michael, Nelson L.; Rerks-Ngarm, Supachai; Mathieson, Bonnie; Marovich, Mary; Currier, Jeffrey R.; Kim, Jerome H.

    2012-01-01

    The Thai HIV phase III prime-boost trial (RV144) using ALVAC-HIV® (vCP1521) and AIDSVAX B/E® was, to our knowledge, the first to demonstrate acquisition efficacy. Vaccine-induced, cell-mediated immune responses were assessed. T cell epitope mapping studies using IFN-γ ELISPOT were performed on PBMC from HIV-1 uninfected vaccine (N=61) and placebo (N=10) recipients using HIV-1 Env peptides. Positive responses were measured in 25 (41%) vaccinees and were predominantly CD4+ T cell mediated. Responses were targeted within the HIV Env region, with 15/25 (60%) of vaccinees recognizing peptides derived from the V2 region of HIV-1 Env, which includes the α4β7 integrin binding site. Intracellular cytokine staining confirmed that Env responses predominated (19/30; 63% of vaccine recipients) and were mediated by polyfunctional effector memory CD4+ T cells, with the majority of responders producing both IL-2 and IFN-γ (12/19; 63%). HIV-Env Ab titers were higher in subjects with IL-2 compared to those without IL-2 secreting HIV-Env specific effector memory T cells. Proliferation assays revealed that HIV Ag-specific T cells were CD4+ with the majority (80%) expressing CD107a. HIV-specific T cell lines obtained from vaccine recipients confirmed V2 specificity, polyfunctionality and functional cytolytic capacity. While the RV144 T cell responses were modest in frequency compared to humoral immune responses, the CD4+ T cell response was directed to HIV-1 Env and more particularly the V2 region. PMID:22529301

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

    PubMed Central

    2012-01-01

    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 PMID:22676626

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

    SciTech Connect

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

    2010-06-01

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

  4. Sunny hours and variations in the prevalence of asthma in schoolchildren according to the International Study of Asthma and Allergies (ISAAC) Phase III in Spain

    NASA Astrophysics Data System (ADS)

    Arnedo-Pena, Alberto; García-Marcos, Luis; Fernández-Espinar, Jorge Fuertes; Bercedo-Sanz, Alberto; Aguinaga-Ontoso, Ines; González-Díaz, Carlos; Carvajal-Urueña, Ignacio; Busquet-Monge, Rosa; Suárez-Varela, Maria Morales; de Andoin, Nagore García; Batlles-Garrido, Juan; Blanco-Quirós, Alfredo; Varela, Angel López-Silvarrey; García-Hernández, Gloria

    2011-05-01

    The objective of this study was to estimate the relationship between the prevalence of asthma in schoolchildren aged 6-7 years and 13-14 years and the mean annual sunny hours (MASH) in Spain, and to explore predictive models for asthma prevalence. The prevalence of asthma was obtained from the International Study of Asthma and Allergies (ISAAC) Phase III 2002-2003, and climate and socio-economic variables from official sources. Nine centres were studied and a further four centres, two of which are in ISAAC, to test the predictive models. Logistic regression was used to estimate adjusted prevalence rates of asthma for each centre, and multiple regression models to study the effects of MASH and other meteorological and socio-economic variables. The adjusted prevalence rate of asthma decreased 0.6% [95% confidence interval (CI) 0.4-0.8%] for the 6-7 years group and 1.1% (95% CI 0.8-1.3%) for the 13-14 years group with an increase in the MASH of 100 h. Relative humidity was negatively associated with asthma in the older age group, and gross province product per capita (GPP) was positively associated with asthma in the younger age group. The predictive models, which included MASH, gender, relative humidity, and GPP, anticipated prevalence rates of asthma without significant differences between the levels observed and those expected in 9 of the11 measurements carried out. The results indicate that sunny hours have a protective effect on the prevalence of asthma in schoolchildren.

  5. Protocol for PIT: a phase III trial of prophylactic irradiation of tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention

    PubMed Central

    Bayman, N; Ardron, D; Ashcroft, L; Baldwin, D R; Booton, R; Darlison, L; Edwards, J G; Lang-Lazdunski, L; Lester, J F; Peake, M; Rintoul, R C; Snee, M; Taylor, P; Lunt, C

    2016-01-01

    Introduction Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure—a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development. Methods and analysis In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians’ discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year. Ethics and dissemination PIT was approved by NRES Committee North West—Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018. Trial registration number ISRCTN04240319; NCT01604005; Pre

  6. Preliminary results of a phase I/II trial of paclitaxel in patients with relapsed or cisplatin-refractory testicular cancer.

    PubMed

    Bokemeyer, C; Schmoll, H J; Natt, F; Knoche, M; Beyer, J; Souchon, R

    1994-01-01

    Paclitaxel represents a novel antitumour agent with demonstrated activity in cisplatin-sensitive tumours, particularly ovarian cancer. In addition, responses to paclitaxel have been observed in patients with cisplatin-refractory ovarian cancer. The role of paclitaxel in the treatment of testicular cancer has not been explored so far. Despite the generally high cure rates in patients with metastatic testicular cancer, patients with relapsed disease not responding to platin-based salvage chemotherapy have an extremely poor prognosis. In a phase I/II trial 10 patients with relapsed, cisplatin-refractory malignant germ-cell tumours were treated with paclitaxel as 6-h infusions (8 patients) or 3-h infusions (2 patients) at doses from 135 mg/m2 to 310 mg/m2 at 3-week intervals. Three patients achieved a response to paclitaxel, but disease recurred shortly in two patients after two and four cycles of therapy, respectively. One patient has remained in marker-negative partial response for more than 5 months. The toxicity of paclitaxel was tolerable for a dose range from 135 mg/m2 to 225 mg/m2. Granulocytopenia, WHO grades 3 and 4, occurred in all patients but was of short duration (median 3 days; range: 2-7 days). Other toxicities such as mucositis (5 patients grade 1), neurotoxicity (1 patient grade 1, 2 patients grade 2), infection (1 patient grade 3) and diarrhoea (1 patient grade 2) were not dose-limiting. There were no hypersensitivity reactions, but 1 patient developed severe myalgias during therapy with paclitaxel. Six patients with documented cisplatin-refractory disease were retreated with cisplatin-based chemotherapy after paclitaxel treatment and, in 4 of these, tumour responses of 3, 4, 5 and more than 5 months duration were achieved. In order to explore the role of paclitaxel in relapsed and/or cisplatin-refractory testicular cancer a phase II study using a 3-h infusion of 225 mg/m2 paclitaxel every 3 weeks, conducted by the German Testicular Cancer Study Group

  7. Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or mantle cell lymphoma.

    PubMed

    William, Basem M; Allen, Mary S; Loberiza, Fausto R; Bociek, Robert Gregory; Bierman, Philip J; Armitage, James O; Vose, Julie M

    2014-04-01

    A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days -11, -8, -5, and -2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m(2)) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day -11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m(2) but it was later decreased to 1 mg/m(2) because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19

  8. A new method for separation and determination of Cr(III) and Cr(VI) in water samples by high-performance liquid chromatography based on anion exchange stationary phase of ionic liquid modified silica.

    PubMed

    Sadeghi, Susan; Moghaddam, Ali Zeraatkar

    2015-12-01

    In this work, N-methylimidazolium-chloride ionic liquid functionalized silica was prepared and used as an anion-exchange stationary phase for separation of chromium species by high-performance liquid chromatography (HPLC) with UV detection at 200 nm. The Cr(VI) as HCr2O7(-) and chelated Cr(III) with potassium hydrogen phthalate (PHP) as Cr(PHP)2 (-) was retained on the prepared column and separated using a mobile phase composed of 5% methanol in 25 mM phosphate buffer at pH 6.5. Several variables affecting the chelation/separation steps were modeled by response surface methodology (RSM) using Box-Behnken (BBD) design. The significance of the independent variables and their interactions were tested by the analysis of variances (ANOVA) with 95% confidence limit. Under the optimized conditions, the Cr(III) and Cr(VI) anionic species were well separated with a single peak for each Cr species at retention times of 2.3 and 4.3 min, respectively. The relationship between the peak area and concentration was linear in the range of 0.025-30 for Cr(III) and 0.5-20 mg L(-1) for Cr(VI) with detection limits of 0.010 and 0.210 mg L(-1) for Cr(III) and Cr(VI), respectively. The proposed method was validated by simultaneous separation and determination of the Cr species in tap and underground water samples without impose to any pretreatment.

  9. Distribution and transport of sediment-bound metal contaminants in the rio grande de tarcoles, costa rica (Central America)

    USGS Publications Warehouse

    Fuller, C.C.; Davis, J.A.; Cain, D.J.; Lamothe, P.J.; Fries Fernandez, T.L.G.; Vargas, J.A.; Murillo, M.M.

    1990-01-01

    A reconnaissance survey of the extent of metal contamination in the Rio Grande de Tarcoles river system of Costa Rica indicated high levels of chromium (Cr) in the fine-grain bed sediments (83 times Cr background or 3000->5000 ??g/g). In the main channel of the river downstream of the San Jose urban area, Cr contamination in sediments was 4-6 times background and remained relatively constant over 50 km to the mouth of the river. Sediment from a mangrove swamp at the river mouth had Cr levels 2-3 times above background. Similar patterns of dilution were observed for lead (Pb) and zinc (Zn) sediment contamination, although the contamination levels were lower. The high affinity of Cr towards particulate phases, probably as Cr(III), allows the use of Cr contamination levels for delineating regions of deposition of fine-grained sediments and dilution of particle associated contaminants during transport and deposition.A reconnaissance survey of the extent of metal contamination in the Rio Grande de Tarcoles river system of Costa Rica indicated high levels of chromium (Cr) in the fine-grain bed sediments (83 times Cr background or 3000->5000 ??g/g). In the main channel of the river downstream of the San Jose urban area, Cr contamination in sediments was 4-6 times background and remained relatively constant over 50 km to the mouth of the river. Sediments from a mangrove swamp at the river mouth had Cr levels 2-3 times above background. Similar patterns of dilution were observed for lead (Pb) and zinc (Zn) sediment contamination, although the contamination levels were lower. The high affinity of Cr towards particulate phases, probably as Cr(III), allows the use of Cr contamination levels for delineating regions of deposition of fine-grained sediments and dilution of particle associated contaminants during transport and deposition.

  10. 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.

    PubMed

    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.

  11. Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: Results of 4 Phase III Trials

    PubMed Central

    Santos, Raul D.; Raal, MD Frederick J.; Catapano, Alberico L.; Witztum, Joseph L; Steinhagen-Thiessen, Elisabeth; Tsimikas, Sotirios

    2015-01-01

    Objective Lp(a) is an independent, causal, genetic risk factor for cardiovascular disease and aortic stenosis. Current pharmacologic lipid-lowering therapies do not optimally lower Lp(a), particularly in patients with familial hypercholesterolemia (FH). Approach and Results In four Phase III trials, 382 patients on maximally tolerated lipid-lowering therapy were randomized 2:1 to weekly subcutaneous mipomersen 200 mg (n=256) or placebo (n=126) for 26 weeks. Populations included homozygous FH (HoFH), heterozygous FH (HeFH) with concomitant coronary artery disease (CAD), severe hypercholesterolemia (HC), and HC at high risk for CAD. Lp(a) was measured eight times between baseline and week 28 inclusive. Of the 382 patients, 57% and 44% had baseline Lp(a) levels >30 mg/dL and >50 mg/dL, respectively. In the pooled analysis, the mean percent decrease (median, interquartile range, IQR) in Lp(a) at 28 weeks was significantly greater in the mipomersen group compared with placebo (-26.4 (-42.8, 5.4) vs. -0.0 (10.7, 15.3), p<0.001). In the mipomersen group in patients with Lp(a) levels >30 mg/dL or >50 mg/dL, attainment of Lp(a) values ≤30 mg/dL or ≤50 mg/dL was most frequent in HoFH and severe HC patients. In the combined groups, modest correlations were present between percent change in apoB and Lp(a) (r=0.43, p<0.001) and LDL-C and Lp(a) (r=0.36, p<0.001) plasma levels. Conclusions Mipomersen consistently and effectively reduced Lp(a) levels in patients with a variety of lipid abnormalities and cardiovascular risk. Modest correlations were present between apoB and Lp(a) lowering but the mechanistic relevance mediating Lp(a) reduction is currently unknown. PMID:25614280

  12. Zabofloxacin versus moxifloxacin in patients with COPD exacerbation: a multicenter, double-blind, double-dummy, randomized, controlled, Phase III, non-inferiority trial.

    PubMed

    Rhee, Chin Kook; Chang, Jung Hyun; Choi, Eu Gene; Kim, Hyun Kuk; Kwon, Yong-Soo; Kyung, Sun Young; Lee, Ji-Hyun; Park, Myung Jae; Yoo, Kwang Ha; Oh, Yeon Mok

    2015-01-01

    A new quinolone, zabofloxacin, has now been developed; hence, a non-inferiority trial is needed to compare this new compound with another widely used quinolone to examine its efficacy and safety for the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. This was a prospective, multicenter, double-blind, double-dummy, randomized, controlled, parallel-group, Phase III, non-inferiority clinical trial designed to compare oral zabofloxacin (367 mg once daily for 5 days) with moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. In all, 345 COPD patients with a moderate COPD exacerbation were enrolled in the study via the outpatient clinics at 31 university hospitals. Clinical per protocol analysis revealed that the clinical cure rate for zabofloxacin was 86.7% and that for moxifloxacin was 86.3% (the rate difference, 0.4%; 95% confidence interval, -7.7%-8.6%). Intention-to-treat analysis revealed clinical cure rates of 77.1% and 77.3% (difference, -0.2%; 95% confidence interval, -9.0%-8.8%), respectively. These results confirm that zabofloxacin is not inferior to moxifloxacin. The favorable microbiological response rate for zabofloxacin was 67.4% and that for moxifloxacin was 79.5% (P=0.22). Patients in the zabofloxacin group showed better patient-oriented outcomes, as measured by EXAcerbations of Chronic Pulmonary Disease Tool-Patient-Reported Outcome and the COPD assessment test scores, than patients in the moxifloxacin group. Adverse drug reactions related to zabofloxacin occurred in 9.7% of cases and those related to moxifloxacin occurred in 9.6% of cases (P=0.97). The dropout rate due to adverse events was 0% (0/175) in the zabofloxacin group and 1.8% (3/167) in the moxifloxacin group (P=0.12). Oral zabofloxacin (367 mg once daily for 5 days) was not inferior to oral moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. PMID:26543359

  13. A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma

    PubMed Central

    Kudchadkar, Ragini; Ernst, Scott; Chmielowski, Bartosz; Redman, Bruce G; Steinberg, Joyce; Keating, Anne; Jie, Fei; Chen, Caroline; Gonzalez, Rene; Weber, Jeffrey

    2015-01-01

    Survivin is a microtubule-associated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a first-in-class survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6-month progression-free survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m2) in combination with YM155 (5 mg/m2 per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6-month PFS rate. Secondary endpoints were objective response rate (ORR), 1-year overall survival (OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixty-four patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m2 and 56 patients received 75 mg/m2 of docetaxel. Six-month PFS rate per Independent Review Committee (IRC) was 34.8% (n = 64; 95% CI, 21.3–48.6%), and per Investigator was 31.3% (n = 64; 95% CI, 19.5–43.9%). The best ORR (complete response [CR] + partial response [PR]) per IRC was 12.5% (8/64). The stable disease (SD) rate was 51.6% (33/64), leading to a CBR (CR + PR + SD) of 64.1% (41/64). Estimated probability of 1-year survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6-month PFS rate ≥20%) was not achieved. PMID:25533314

  14. Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study

    PubMed Central

    Li, Jing; Kang, Jian; Wang, Changzheng; Yang, Jing; Wang, Linda; Kottakis, Ioannis; Humphries, Michael

    2016-01-01

    Purpose Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. Methods This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). Results A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; P<0.001) and ACQ (49.5% vs 35.5%; LSM=-0.51 vs -0.34; P=0.002) scores vs placebo. Total and nighttime symptom scores reduced significantly with omalizumab vs placebo (LSM-TD=-0.21, P=0.048 and -0.12, P=0.011, respectively). Although the study was not powered to study differences in exacerbation rates (P=0.097), exacerbations in winter months were less frequent in the omalizumab vs placebo group (2 vs 21). Adverse event and severe adverse event rates were comparable between omalizumab and placebo. Conclusions Omalizumab improves lung function, quality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile. PMID:27126725

  15. Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: a subanalysis of the phase III, randomized SATURN study.

    PubMed

    Wu, Yi-Long; Kim, Joo-Hang; Park, Keunchil; Zaatar, Adel; Klingelschmitt, Gaëlle; Ng, Christina

    2012-08-01

    Maintenance therapy, commenced immediately after the completion of first-line chemotherapy, is a promising strategy for improving treatment outcomes in patients with non-small-cell lung cancer (NSCLC). The global phase III SequentiAl Tarceva in UnResectable NSCLC (SATURN) study evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib as maintenance treatment in NSCLC patients without progression after first-line chemotherapy. We report a retrospective subanalysis of Asian patients enrolled in SATURN. Patients with advanced NSCLC with no evidence of progression after four cycles of chemotherapy were randomized to receive erlotinib 150 mg/day or placebo, until progressive disease or limiting toxicity. The co-primary endpoints of SATURN were progression-free survival (PFS) in all patients and in those with positive EGFR immunohistochemistry (IHC) status. Secondary endpoints included overall survival (OS), disease control rate, safety, quality of life (QoL) and biomarker analyses. In total, 126 patients from East and South-East Asian centers were randomized (14% of the intent-to-treat population): 88 from Korea, 28 from China and 10 from Malaysia; one patient was excluded from this analysis due to Indian ethnicity. PFS was significantly prolonged in the erlotinib treatment arm, both overall (hazard ratio [HR]: 0.57; p=0.0067) and in patients with EGFR IHC-positive disease (HR=0.50; p=0.0057). There was a trend towards an increase in OS, which reached statistical significance in the EGFR IHC-positive subgroup (p=0.0233). The overall response rate was significantly higher with erlotinib compared with placebo (24% versus 5%; p=0.0025). Erlotinib was generally well tolerated and had no negative impact on QoL in this subpopulation. The most common treatment-related adverse events were rash, diarrhea and pruritus. Erlotinib was effective and well tolerated in Asian patients, producing benefits consistent with those

  16. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials

    PubMed Central

    Xu, Liang; Wu, Xiaobo; Hu, Chun; Zhang, Zhiying; Zhang, Le; Liang, Shujing; Xu, Yingchun; Zhang, Fengchun

    2016-01-01

    Nowadays, the philosophy of treating metastatic breast cancer (MBC) is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015) comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS), and the secondary end points were the progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 toxicities. The pooled hazard ratio (HR) and pooled risk ratio (RR) were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84–0.96, P=0.002), PFS (HR 0.81, 95% CI 0.76–0.88, P<0.001), and ORR (RR 1.72, 95% CI 1.34–2.21, P<0.001). Notably, subgroup analysis failed to favor the targeted agent-based combination in terms of OS (HR 1.08, 95% CI 0.89–1.31, P=0.365), PFS (HR 1.09, 95% CI 0.88–1.35, P=0.433), and ORR (RR 1.60, 95% CI 0.69–3.71, P=0.278) compared with single agent. In addition, although more hematological and gastrointestinal toxicities were observed in the doublet agents group, they were acceptable and manageable. Taken together, when compared with single-agent therapy, doublet agents should be considered a treatment option because of the superior efficacy and the manageable safety profile for the prior anthracycline- and taxane-treated MBC patients. PMID:27445497

  17. Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY‐3+)

    PubMed Central

    Leroy, Vincent; Angus, Peter; Bronowicki, Jean‐Pierre; Dore, Gregory J.; Hezode, Christophe; Pianko, Stephen; Pol, Stanislas; Stuart, Katherine; Tse, Edmund; McPhee, Fiona; Bhore, Rafia; Jimenez‐Exposito, Maria Jesus

    2016-01-01

    Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination of daclatasvir (DCV; pangenotypic nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY‐3+ study (N = 50) evaluated DCV‐SOF with ribavirin (RBV) in treatment‐naïve (n = 13) or treatment‐experienced (n = 37) genotype 3‐infected patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open‐label DCV‐SOF (60 + 400 mg daily) with weight‐based RBV for 12 or 16 weeks. The primary endpoint was sustained virological response at post‐treatment week 12 (SVR12). SVR12 (intention‐to‐treat) was 90% overall (45 of 50): 88% (21 of 24) in the 12‐week (91% observed) and 92% (24 of 26) in the 16‐week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31 of 36): 83% (15 of 18) in the 12‐week (88% observed) and 89% (16 of 18) in the 16‐week group; for treatment‐experienced patients with cirrhosis, these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 14), respectively. One patient (12‐week group) did not enter post‐treatment follow‐up (death unrelated to treatment). There were 4 relapses (2 per group) and no virological breakthroughs. The most common adverse events (AEs) were insomnia, fatigue, and headache. There were no discontinuations for AEs and no treatment‐related serious AEs. Conclusion: The all‐oral regimen of DCV‐SOF‐RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3‐infected patients with advanced liver disease, irrespective of past HCV treatment experience. (Hepatology 2016

  18. Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies

    PubMed Central

    Spitz, Aaron; Gittelman, Marc; Karsh, Lawrence I; Dragnic, Sanja; Soliman, Ahmed M; Lele, Aditya; Gruca, Damian; Norton, Michael

    2016-01-01

    Introduction Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels. Methods In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks. Results Pooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks. Conclusion Both 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted.

  19. A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: Follow-up of a gynecologic oncology group study

    SciTech Connect

    Rotman, Marvin . E-mail: mrotman@downstate.edu; Sedlis, Alexander; Piedmonte, Marion R.; Bundy, Brian; Lentz, Samuel S.; Muderspach, Laila I.; Zaino, Richard J.

    2006-05-01

    Purpose: To investigate, in a phase III randomized trial, whether postoperative external-beam irradiation to the standard pelvic field improves the recurrence-free interval and overall survival (OS) in women with Stage IB cervical cancers with negative lymph nodes and certain poor prognostic features treated by radical hysterectomy and pelvic lymphadenectomy. Methods and Materials: Eligible patients had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the following features: more than one third (deep) stromal invasion, capillary lymphatic space involvement, and tumor diameter of 4 cm or more. The study group included 277 patients: 137 randomized to pelvic irradiation (RT) and 140 randomized to observation (OBS). The planned pelvic dose was from 46 Gy in 23 fractions to 50.4 Gy in 28 fractions. Results: Of the 67 recurrences, 24 were in the RT arm and 43 were in the OBS arm. The RT arm showed a statistically significant (46%) reduction in risk of recurrence (hazard ratio [HR] = 0.54, 90% confidence interval [CI] = 0.35 to 0.81, p = 0.007) and a statistically significant reduction in risk of progression or death (HR = 0.58, 90% CI = 0.40 to 0.85, p = 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences were seen with RT in patients with adenocarcinoma or adenosquamous histologies relative to others (HR for RT by histology interaction = 0.23, 90% CI = 0.07 to 0.74, p = 0.019). After an extensive follow-up period, 67 deaths have occurred: 27 RT patients and 40 OBS patients. The improvement in overall survival (HR = 0.70, 90% CI = 0.45 to 1.05, p = 0.074) with RT did not reach statistical significance. Conclusions: Pelvic radiotherapy after radical surgery significantly reduces the risk of recurrence and prolongs progression-free survival in women with Stage IB cervical cancer. RT appears to be particularly beneficial for patients with adenocarcinoma or

  20. Assessing Potential Impacts of CO2 Leakage on Shallow Groundwater Quality in the SECARB Phase III Early Test site Using Single-well Push-Pull Tests

    NASA Astrophysics Data System (ADS)

    Yang, C.; Mickler, P. J.; Reedy, R. C.; Scanlon, B. R.

    2012-12-01

    A single-well push-pull test was conducted in the Cranfield shallow aquifer, the SECARB Phase III early test site, for assessing potential impacts of CO2 leakage on groundwater quality. A total of 3800 liter of groundwater equilibrated with CO2 gas at a partial pressure of 1.105 Pa was injected into a confined sand interval at ~ 70 m depth. NaBr solution was added to the injected solution as tracer. The injected groundwater incubated within the interval for about two days. Chemical parameters (pH, temperature, alkalinity, and electric conductivity) were measured on-site and water samples were collected for chemical (major ions, trace elements, and dissolved inorganic carbon, DIC) as well as for stable carbon isotopic analyses. Mineralogical analyses using XR-D and SEM techniques indicate that aquifer sediments are dominated by silicates. Concentrations of the Br tracer in the recovered samples show mixing of background water with the injected solution. Major ions, especially, Ca, Mg, K, and Si show obvious enrichment, indicating that mobilization of these ions occurred from aquifer sediments to groundwater and may be dominated by dissolution of silicates and possible carbonate minerals. δ13C of DIC of the recovered samples may also suggest potential dissolution of carbonates. Concentrations of trace elements show mobilization after injection of CO2 enriched groundwater. Mobilization of trace elements could be due to co-dissolution of silicates and carbonates and desorption from the surface of aquifer sediments. However, mass balance calculations suggest that ion mobilization is limited and; therefore, potential risks of CO2 are low, especially for arsenic and lead with concentrations in the recovered samples ~30 times less than the EPA maximum contamination level. Results of the single-well push-pull test were also compared to a laboratory batch experiment of water-rock-CO2 interactions. Overall reaction rates of most ions estimated are higher in the batch

  1. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

    PubMed Central

    Fenaux, Pierre; Mufti, Ghulam J; Hellstrom-Lindberg, Eva; Santini, Valeria; Finelli, Carlo; Giagounidis, Aristoteles; Schoch, Robert; Gattermann, Norbert; Sanz, Guillermo; List, Alan; Gore, Steven D; Seymour, John F; Bennett, John M; Byrd, John; Backstrom, Jay; Zimmerman, Linda; McKenzie, David; Beach, C L; Silverman, Lewis R

    2014-01-01

    Summary Background Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m² per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French–American–British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1–26·9), median overall survival was 24·5 months (9·9–not reached) for the azacitidine group versus 15·0 months (5·6–24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43–0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1–58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7–34·3) in the conventional care group (p<0·0001). Peripheral cytopenias were the most

  2. A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder.

    PubMed

    Sambunaris, Angelo; Bose, Anjana; Gommoll, Carl P; Chen, Changzheng; Greenberg, William M; Sheehan, David V

    2014-02-01

    Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor; an extended-release (ER) formulation allows for once-daily dosing. This phase III study (NCT01034462) evaluated the efficacy, the safety, and the tolerability of 40 to 120 mg/d of levomilnacipran ER versus placebo in the treatment of patients (18-80 y) with major depressive disorder. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comprised a 1-week single-blind, placebo run-in period; an 8-week double-blind treatment; and a 2-week double-blind down-taper period. The primary efficacy parameter was total score change from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS); the secondary efficacy was the Sheehan Disability Scale. Analysis was performed using the mixed-effects model for repeated measures on a modified intent-to-treat population. A total of 434 patients received at least 1 dose of double-blind treatment (safety population); 429 patients also had 1 or more postbaseline MADRS assessments (modified intent-to-treat population). The least squares mean differences and 95% confidence interval were statistically significant in favor of levomilnacipran ER versus placebo for the MADRS total score (-3.095 [-5.256, -0.935]; P = 0.0051) and the SDS total score (-2.632 [-4.193, -1.070]; P = 0.0010) change from baseline to week 8. Adverse events were reported in 61.8% of the placebo patients and in 81.6% of the levomilnacipran ER patients. Frequently reported adverse events (≥ 5% in levomilnacipran ER and twice the rate of placebo) were nausea, dizziness, constipation, tachycardia, urinary hesitation, hyperhidrosis, insomnia, vomiting, hypertension, and ejaculation disorder. In conclusion, there was a statistically significant difference in the score change from baseline to week 8 between levomilnacipran ER and placebo on several depression rating scales, reflecting symptomatic

  3. Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

    SciTech Connect

    Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna; Saarilahti, Kauko; Atula, Timo; Collan, Juhani; Salli, Eero; Kortesniemi, Mika; Uusi-Simola, Jouni; Vaelimaeki, Petteri; Maekitie, Antti; Seppaenen, Marko; Minn, Heikki; Revitzer, Hannu; Kouri, Mauri; Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro; Savolainen, Sauli; Joensuu, Heikki

    2012-01-01

    Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by use of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was

  4. Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies

    PubMed Central

    Spitz, Aaron; Gittelman, Marc; Karsh, Lawrence I; Dragnic, Sanja; Soliman, Ahmed M; Lele, Aditya; Gruca, Damian; Norton, Michael

    2016-01-01

    Introduction Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels. Methods In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks. Results Pooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks. Conclusion Both 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted. PMID:27602344

  5. Geomechanical variability within the D-E Member of the lower Tuscaloosa Formation supporting the SECARB Phase III CO2 Injection Program

    NASA Astrophysics Data System (ADS)

    Rinehart, A. J.; Dewers, T. A.; Broome, S.; Newell, P.

    2014-12-01

    We characterize the mechanical properties at near in-situ conditions of Lower Tuscaloosa lithologies at the Cranfield-site Southeast Regional Carbon Sequestration Partnership (SECARB) Phase III injection program. Four lithofacies in the injection horizon are chosen for strength testing, including: chlorite-cemented conglomeratic sandstone (CSS); mixed chlorite- and quartz-cemented cross-bedded fine sandstone (XSS); quartz-cemented tabular very fine sandstone (TSS); and quartz-cemented siltstone (SiS). Each lithofacies had 25-mm diameter by at least 50-mm length samples plugged. We performed a suite of compression tests for the sandstone at 100°C and pore pressure of 30 MPa, including near-zero effective confining pressure triaxial test, axisymmetric compression tests, and hydrostatic compression test. Sandstones were saturated with supercritical CO2-equilibrated brine with 30 MPa pore pressure. SiS samples were equilibrated at a constant relative humidity of 77% at 100°C. TSS had the largest yield and failure envelopes. XSS had slightly smaller yield and failure envelopes. CSS was by far the weakest. The sandy facies' effective unconfined tests showed rounded peaks, indicating viscous deformation during damage. SiS had strengths intermediate to TSS and XSS, and CSS. The chemical environment mechanically changed CSS, with cement type exerting control on strength. Constitutive behavior is modeled with elasto-plastic and viscous models. Essential features describing mechanical behavior include non-associative plasticity, stress-invariant dependent failure, elliptical cap surface, kinematic and isotropic hardening, non linear elasticity and elastic-plastic coupling. We discuss the influence of CO2 injection on geomechanical properties. This material is based upon work supported as part of the Center for Frontiers of Subsurface Energy Security, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy

  6. A historically-controlled Phase III study in adults to characterize the acceptability of a process change for manufacturing inactivated quadrivalent influenza vaccine

    PubMed Central

    2014-01-01

    Background An inactivated quadrivalent influenza vaccine (QIV) was recently licenced in the US as a thimerosal-free formulation presented in a pre-filled syringe. A multidose presentation is preferred in some settings due to reduced acquisition and cold storage costs. We assessed the immunogenicity and safety of a thimerosal-containing QIV formulated using a new manufacturing process for presentation in multidose vials. Methods Two Phase III non-randomized studies separately evaluated inactivated trivalent influenza vaccine (TIV; 2010–2011; historical control) and a QIV (2011–2012). The QIV contained the same strains as the TIV plus an additional B strain. Both vaccines contained thimerosal to allow multidose presentation: this preservative was added to the QIV during the final formulation step using a new process, whereas it was added to the TIV early in the manufacturing process using an established method. The TIV study included 50 and 70 subjects aged 18–60 and >60 years, respectively; the QIV study included 56 subjects in each age stratum. Immunogenicity was assessed using hemagglutination-inhibition (HI) assays. Reactogenicity was assessed during the 4-day post-vaccination periods and unsolicited adverse events (AEs) were assessed during the 21-day post-vaccination periods. Results The TIV and QIV were immunogenic in both age strata. With the QIV and TIV respectively, the seroconversion rates were 48.2–62.7% and 71.4–83.7% for influenza A, and 33.9–62.5% and 67.3–72.9% for influenza B. With the QIV and TIV respectively, the seroprotection rates were 92.9–98.2% and 98.2–100% for influenza A, and 88.6–100% and 95.9–98.6% for influenza B. Pre-vaccination titers were higher in the QIV versus TIV study which confounds a direct comparison and likely explains the lower seroconversion rates observed in the QIV study. There were no safety concerns raised with TIV or QIV. Conclusions The thimerosal-containing QIV formulated using a new process

  7. Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study

    PubMed Central

    Steinfeld, Serge D; Tant, Laure; Burmester, Gerd R; Teoh, Nick KW; Wegener, William A; Goldenberg, David M; Pradier, Olivier

    2006-01-01

    This open-label, phase I/II study investigated the safety and efficacy of epratuzumab, a humanised anti-CD22 monoclonal antibody, in the treatment of patients with active primary Sjögren's syndrome (pSS). Sixteen Caucasian patients (14 females/2 males, 33–72 years) were to receive 4 infusions of 360 mg/m2 epratuzumab once every 2 weeks, with 6 months of follow-up. A composite endpoint involving the Schirmer-I test, unstimulated whole salivary flow, fatigue, erythrocyte sedimentation rate (ESR), and immunoglobulin G (IgG) was devised to provide a clinically meaningful assessment of response, defined as a ≥20% improvement in at least two of the aforementioned parameters, with ≥20% reduction in ESR and/or IgG considered as a single combined criterion. Fourteen patients received all infusions without significant reactions, 1 patient received 3, and another was discontinued due to a mild acute reaction after receiving a partial infusion. Three patients showed moderately elevated levels of Human anti-human (epratuzumab) antibody not associated with clinical manifestations. B-cell levels had mean reductions of 54% and 39% at 6 and 18 weeks, respectively, but T-cell levels, immunoglobulins, and routine safety laboratory tests did not change significantly. Fifty-three percent achieved a clinical response (at ≥20% improvement level) at 6 weeks, with 53%, 47%, and 67% responding at 10, 18, and 32 weeks, respectively. Approximately 40%–50% responded at the ≥30% level, while 10%–45% responded at the ≥50% level for 10–32 weeks. Additionally, statistically significant improvements were observed in fatigue, and patient and physician global assessments. Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy. Thus, epratuzumab appears to be a promising therapy in active pSS, suggesting that further studies be conducted. PMID:16859536

  8. Challenges of Correlating pH Change with Relief of Clinical Symptoms in Gastro Esophageal Reflux Disease: A Phase III, Randomized Study of Zegerid versus Losec

    PubMed Central

    Walker, Dave; Ng Kwet Shing, Richard; Jones, Deborah; Gruss, Hans-Jurgen; Reguła, Jarosław

    2015-01-01

    Background Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD). Methods Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20mg) or Losec (20mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes). Results Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0–30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns. Conclusions Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in

  9. Oral Mucositis Prevention By Low-Level Laser Therapy in Head-and-Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy: A Phase III Randomized Study

    SciTech Connect

    Gouvea de Lima, Aline; Villar, Rosangela Correa; Castro, Gilberto de; Antequera, Reynaldo; Gil, Erlon; Rosalmeida, Mauro Cabral; Federico, Miriam Hatsue Honda; Snitcovsky, Igor Moises Longo

    2012-01-01

    Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm{sup 2} or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might

  10. Paclitaxel injection concentrate for nanodispersion versus nab-paclitaxel in women with metastatic breast cancer: a multicenter, randomized, comparative phase II/III study.

    PubMed

    Jain, Minish M; Gupte, Smita U; Patil, Shekhar G; Pathak, Anand B; Deshmukh, Chetan D; Bhatt, Niraj; Haritha, Chiramana; Govind Babu, K; Bondarde, Shailesh A; Digumarti, Raghunadharao; Bajpai, Jyoti; Kumar, Ravi; Bakshi, Ashish V; Bhattacharya, Gouri Sankar; Patil, Poonam; Subramanian, Sundaram; Vaid, Ashok K; Desai, Chirag J; Khopade, Ajay; Chimote, Geetanjali; Bapsy, Poonamalle P; Bhowmik, Shravanti

    2016-02-01

    Paclitaxel is widely used in the treatment of patients with metastatic breast cancer (MBC). Formulations of paclitaxel contain surfactants and solvents or albumin derived from human blood. The use of co-solvents such as polyoxyethylated castor oil is thought to contribute to toxicity profile and hypersensitivity reactions as well as leaching of plasticizers from polyvinyl chloride bags and infusion sets. Currently, nab-paclitaxel, an albumin-bound paclitaxel in nanometer range continues to be the preferred taxane formulation used in clinic. This study (CTRI/2010/091/001116) investigated the efficacy and tolerability of a polyoxyethylated castor oil- and albumin-free formulation of paclitaxel [paclitaxel injection concentrate for nanodispersion (PICN)] compared with nab-paclitaxel in women with refractory MBC. The current study was a multicenter, open-label, parallel-group, randomized, comparative phase II/III trial evaluating the efficacy and safety of PICN (260 mg/m(2) [n = 64] and 295 mg/m(2) [n = 58] every 3 weeks) compared with nab-paclitaxel (260 mg/m(2) every 3 weeks [n = 58]) in women 18 and 70 years old with confirmed MBC. Overall response rate (ORR) was assessed with imaging every 2 cycles. An independent analysis of radiologic data was performed for evaluable patients. Progression-free survival (PFS) was a secondary efficacy measure. Independent radiologist-assessed ORRs in the evaluable population of women aged ≥70 years were 35, 49, and 43 % in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Median PFS in the evaluable population was 23, 35, and 34 weeks in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Adverse events occurred in similar proportions of patients across treatment arms. Hypersensitivity reactions were not frequently observed with the clinical use of PICN across the treatment cohorts. In women with metastatic breast cancer, PICN at 260 and 295 mg/m(2

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

    PubMed

    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 < 0.013): rCBV decreased when initial rCBV was ≥ 1.0 (Group_rCBV_M0 > 1) and rCBV increased when initial rCBV was < 1.0 (Group_rCBV_M0 < 1). Mapping of 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 < 1 presented a decrease of Low_CBVTUMOR volume with an increase of Normal_ and High_CBV TUMOR volume after treatment. Pre and post-treatment CBV measurements with DSC-MRI characterized tumor perfusion evolution in GBM patients treated with RT combined to Tipifarnib; showing variations in favour of tumor perfusion

  12. 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

    PubMed Central

    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; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

    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 dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

  13. A Phase III, Double-Blind, Placebo-Controlled, Flexible-Dose Study of Levomilnacipran Extended-Release in Patients With Major Depressive Disorder

    PubMed Central

    Bose, Anjana; Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Sheehan, David V.

    2014-01-01

    Abstract Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor; an extended-release (ER) formulation allows for once-daily dosing. This phase III study (NCT01034462) evaluated the efficacy, the safety, and the tolerability of 40 to 120 mg/d of levomilnacipran ER versus placebo in the treatment of patients (18-80 y) with major depressive disorder. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comprised a 1-week single-blind, placebo run-in period; an 8-week double-blind treatment; and a 2-week double-blind down-taper period. The primary efficacy parameter was total score change from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS); the secondary efficacy was the Sheehan Disability Scale. Analysis was performed using the mixed-effects model for repeated measures on a modified intent-to-treat population. A total of 434 patients received at least 1 dose of double-blind treatment (safety population); 429 patients also had 1 or more postbaseline MADRS assessments (modified intent-to-treat population). The least squares mean differences and 95% confidence interval were statistically significant in favor of levomilnacipran ER versus placebo for the MADRS total score (−3.095 [−5.256, −0.935]; P = 0.0051) and the SDS total score (−2.632 [−4.193, −1.070]; P = 0.0010) change from baseline to week 8. Adverse events were reported in 61.8% of the placebo patients and in 81.6% of the levomilnacipran ER patients. Frequently reported adverse events (≥5% in levomilnacipran ER and twice the rate of placebo) were nausea, dizziness, constipation, tachycardia, urinary hesitation, hyperhidrosis, insomnia, vomiting, hypertension, and ejaculation disorder. In conclusion, there was a statistically significant difference in the score change from baseline to week 8 between levomilnacipran ER and placebo on several depression rating scales

  14. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials.

    PubMed

    Xu, Liang; Wu, Xiaobo; Hu, Chun; Zhang, Zhiying; Zhang, Le; Liang, Shujing; Xu, Yingchun; Zhang, Fengchun

    2016-01-01

    Nowadays, the philosophy of treating metastatic breast cancer (MBC) is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015) comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS), and the secondary end points were the progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 toxicities. The pooled hazard ratio (HR) and pooled risk ratio (RR) were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84-0.96, P=0.002), PFS (HR 0.81, 95% CI 0.76-0.88, P<0.001), and ORR (RR 1.72, 95% CI 1.34-2.21, P<0.001). Notably, subgroup analysis failed to favor the targeted agent-based combination in terms of OS (HR 1.08, 95% CI 0.89-1.31, P=0.365), PFS (HR 1.09, 95% CI 0.88-1.35, P=0.433), and ORR (RR 1.60, 95% CI 0.69-3.71, P=0.278) compared with single agent. In addition, although more hematological and gastrointestinal toxicities were observed in the doublet agents group, they were acceptable and manageable. Taken together, when compared with single-agent therapy, doublet agents should be considered a treatment option because of the superior efficacy and the manageable safety profile for the prior anthracycline- and taxane-treated MBC patients. PMID:27445497

  15. Phase I/II Study Evaluating Early Tolerance in Breast Cancer Patients Undergoing Accelerated Partial Breast Irradiation Treated With the MammoSite Balloon Breast Brachytherapy Catheter Using a 2-Day Dose Schedule

    SciTech Connect

    Wallace, Michelle; Martinez, Alvaro; Mitchell, Christina; Chen, Peter Y.; Ghilezan, Mihai; Benitez, Pamela; Brown, Eric; Vicini, Frank

    2010-06-01

    Purpose: Initial Phase I/II results using balloon brachytherapy to deliver accelerated partial breast irradiation (APBI) in 2 days in patients with early-stage breast cancer are presented. Materials and Methods: Between March 2004 and August 2007, 45 patients received adjuvant radiation therapy after lumpectomy with balloon brachytherapy in a Phase I/II trial delivering 2800 cGy in four fractions of 700 cGy. Toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria for Adverse Events v3.0 scale and cosmesis was documented at >=6 months. Results: The median age was 66 years (range, 48-83) and median skin spacing was 12 mm (range, 8-24). The median follow-up was 11.4 months (5.4-48 months) with 21 patients (47%) followed >=1 year, 11 (24%) >=2 years, and 7 (16%) >=3 years. At <6 months (n = 45), Grade II toxicity rates were 9% radiation dermatitis, 13% breast pain, 2% edema, and 2% hyperpigmentation. Grade III breast pain was reported in 13% (n = 6). At >=6 months (n = 43), Grade II toxicity rates were: 2% radiation dermatitis, 2% induration, and 2% hypopigmentation. Grade III breast pain was reported in 2%. Infection was 13% (n = 6) at <6 months and 5% (n = 2) at >=6 months. Persistent seroma >=6 months was 30% (n = 13). Fat necrosis developed in 4 cases (2 symptomatic). Rib fractures were seen in 4% (n = 2). Cosmesis was good/excellent in 96% of cases. Conclusions: Treatment with balloon brachytherapy using a 2-day dose schedule resulted acceptable rates of Grade II/III chronic toxicity rates and similar cosmetic results observed with a standard 5-day accelerated partial breast irradiation schedule.

  16. Bicyclic and acyclic diamides: comparison of their aqueous phase binding constants with Nd(III), Am(III), Pu(IV), Np(V), Pu(VI), and U(VI).

    PubMed

    Sinkov, Serguei I; Rapko, Brian M; Lumetta, Gregg J; Hay, Benjamin P; Hutchison, James E; Parks, Bevin W

    2004-12-27

    This report describes affinity measurements for two, water-soluble, methyl-alkylated diamides incorporating the malonamide functionality, N,N,N',N' tetramethylmalonamide (TMMA) and a bicyclic diamide (1a), toward actinide metal cations (An) in acidic nitrate solutions. Ligand complexation to actinides possessing oxidation states ranging from +3 to +6 was monitored through optical absorbance spectroscopy, and formation constants were obtained from the refinement of the spectrophotometric titration data sets. Species analysis gives evidence for the formation of 1, 4, 1, and 2 spectrophotometrically observable complexes by TMMA to An(III, IV, V, and VI), respectively, while for 1a, the respective numbers are 3, 4, 2, and 2. Consistent with the preorganization of 1a toward actinide binding, a significant difference is found in the magnitudes of their respective formation constants at each complexation step. It has been found that the binding affinity for TMMA follows the well-established order An(V) < An(III) < An(VI) < An(IV). However, with 1a, Np(V) forms stronger complexes than Am(III). The complexation of 1a with Np(V) and Pu(VI) at an acidity of 1.0 M is followed by reduction to Np(IV) and Pu(IV), whereas TMMA does not perturb the initial oxidation state for these dioxocations. These measurements of diamide binding affinity mark the first time single-component optical absorbance spectra have been reported for a span of actinide-diamide complexes covering all common oxidation states in aqueous solution.

  17. Application of aqueous two-phase systems for the development of a new method of cobalt(II), iron(III) and nickel(II) extraction: a green chemistry approach.

    PubMed

    Patrício, Pamela da Rocha; Mesquita, Maiby Cabral; da Silva, Luis Henrique Mendes; da Silva, Maria C Hespanhol

    2011-10-15

    We have investigated the extraction behavior of the metallic ions Co(II), Fe(III) and Ni(II) as a function of the amount of potassium thiocyanate used as an extracting agent, using the following aqueous two-phase systems (ATPS): PEO + (NH(4))(2)SO(4) + H(2)O, PEO + Li(2)SO(4) + H(2)O, L35 + (NH(4))(2)SO(4) + H(2)O and L35 + (Li)(2)SO(4)+H(2)O. Metal extraction from the salt-rich phase to the polymer-rich phase is affected by the following parameters: amount of added extractant, pH, and the nature of the electrolyte and polymer that forms the ATPS. Maximal extraction percentages were obtained for Co(II) (99.8%), Fe(III) (12.7%) and Ni(II) (3.17%) when the ATPS was composed of PEO1500 + (NH(4))(2)SO(4) + H(2)O containing 1.4 mmol of KSCN at pH 4.0, providing separation factors as high as S(Co, Fe) = 3440 and S(Co, Ni) = 15,300. However, when the same ATPS was used at pH 2.0, the maximal extraction percentages for iron and nickel were 99.5% and 4.34%, respectively, with S(Fe, Ni) equal to 4380. The proposed technique was shown to be efficient in the extraction of Co(II) and Fe(III), with large viability for the selective separation of Co(II) and Fe(III) ions in the presence of Ni(II). PMID:21864977

  18. Application of aqueous two-phase systems for the development of a new method of cobalt(II), iron(III) and nickel(II) extraction: a green chemistry approach.

    PubMed

    Patrício, Pamela da Rocha; Mesquita, Maiby Cabral; da Silva, Luis Henrique Mendes; da Silva, Maria C Hespanhol

    2011-10-15

    We have investigated the extraction behavior of the metallic ions Co(II), Fe(III) and Ni(II) as a function of the amount of potassium thiocyanate used as an extracting agent, using the following aqueous two-phase systems (ATPS): PEO + (NH(4))(2)SO(4) + H(2)O, PEO + Li(2)SO(4) + H(2)O, L35 + (NH(4))(2)SO(4) + H(2)O and L35 + (Li)(2)SO(4)+H(2)O. Metal extraction from the salt-rich phase to the polymer-rich phase is affected by the following parameters: amount of added extractant, pH, and the nature of the electrolyte and polymer that forms the ATPS. Maximal extraction percentages were obtained for Co(II) (99.8%), Fe(III) (12.7%) and Ni(II) (3.17%) when the ATPS was composed of PEO1500 + (NH(4))(2)SO(4) + H(2)O containing 1.4 mmol of KSCN at pH 4.0, providing separation factors as high as S(Co, Fe) = 3440 and S(Co, Ni) = 15,300. However, when the same ATPS was used at pH 2.0, the maximal extraction percentages for iron and nickel were 99.5% and 4.34%, respectively, with S(Fe, Ni) equal to 4380. The proposed technique was shown to be efficient in the extraction of Co(II) and Fe(III), with large viability for the selective separation of Co(II) and Fe(III) ions in the presence of Ni(II).

  19. As(III) and As(V) removal from the aqueous phase via adsorption onto acid mine drainage sludge (AMDS) alginate beads and goethite alginate beads.

    PubMed

    Lee, Hongkyun; Kim, Dohyeong; Kim, Jongsik; Ji, Min-Kyu; Han, Young-Soo; Park, Young-Tae; Yun, Hyun-Shik; Choi, Jaeyoung

    2015-07-15

    Acid mine drainage sludge (AMDS) is a solid waste generated following the neutralization of acid mine drainage (AMD). This material entrapped in calcium alginate was investigated for the sorption of As(III) and As(V). Three different adsorbent materials were prepared: AMDS alginate beads (AABs), goethite alginate beads (GABs), and pure alginate beads. The effects of pH and the adsorption kinetics were investigated, and the adsorption isotherms were also evaluated. The optimum pH range using the AABs was determined to be within 2-10 for As(III) and 2-9 for As(V). Adsorption equilibrium data were evaluated using the Langmuir isotherm model, and the maximum adsorption capacity qmax was 18.25 and 4.97 mg g(-1) for As(III) on AAB and GAB, respectively, and 21.79 and 10.92 mg g(-1) for As(V) on AAB and GAB, respectively. The adsorption of As(III) and As(V) was observed to follow pseudo-second order kinetics. The As K-edge X-ray absorption near-edge structure (XANES) revealed that the adsorbed As(III) on the AABs was oxidized to As(V) via manganese oxide in the AMDS. PMID:25804789

  20. As(III) and As(V) removal from the aqueous phase via adsorption onto acid mine drainage sludge (AMDS) alginate beads and goethite alginate beads.

    PubMed

    Lee, Hongkyun; Kim, Dohyeong; Kim, Jongsik; Ji, Min-Kyu; Han, Young-Soo; Park, Young-Tae; Yun, Hyun-Shik; Choi, Jaeyoung

    2015-07-15

    Acid mine drainage sludge (AMDS) is a solid waste generated following the neutralization of acid mine drainage (AMD). This material entrapped in calcium alginate was investigated for the sorption of As(III) and As(V). Three different adsorbent materials were prepared: AMDS alginate beads (AABs), goethite alginate beads (GABs), and pure alginate beads. The effects of pH and the adsorption kinetics were investigated, and the adsorption isotherms were also evaluated. The optimum pH range using the AABs was determined to be within 2-10 for As(III) and 2-9 for As(V). Adsorption equilibrium data were evaluated using the Langmuir isotherm model, and the maximum adsorption capacity qmax was 18.25 and 4.97 mg g(-1) for As(III) on AAB and GAB, respectively, and 21.79 and 10.92 mg g(-1) for As(V) on AAB and GAB, respectively. The adsorption of As(III) and As(V) was observed to follow pseudo-second order kinetics. The As K-edge X-ray absorption near-edge structure (XANES) revealed that the adsorbed As(III) on the AABs was oxidized to As(V) via manganese oxide in the AMDS.

  1. The peats of Costa Rica

    SciTech Connect

    Thayer, G.R.

    1991-01-01

    Peat has been identified in Cost Rica, and an economic analysis of energy applications for peat has been done. About 1000 km{sup 2} of Cost Rica has the potential of being covered by peat. The Talamanca Mountains and the northeastern plains contain most of the Costa Rican peat. Specific bogs have been identified by the Medio Queso River in north-central Costa Rica and near El Cairo, Moin, and the Limon airport in northeastern Costa Rica. The Medio Queso bog, which is supplying peat for use as a carrier for nitrogen-fixing bacteria, and the El Cairo bog, which has been identified as a source of horticultural peat for nearby ornamental plant farms, are of special interest. The economics of three energy applications of peat were examined -- as a fuel in large boilers, as a fuel in small boilers, and as an oil substitute in a cement plant. A facility using coal would have the same total costs as one using peat if coal prices were $45 and $30 per metric ton (used for large boilers and a cement plant, respectively). A facility using Bunker C or diesel would have the same total cost as one using peat if oil prices were $0.11, $0.08, and $0.06 per liter (used for large boilers, small boilers, and a cement plant, respectively). In all three cases, the costs for peat were comparable or less than the costs for coal and oil at 1987 prices. 6 refs., 8 figs.

  2. Randomized Phase II/III Trial Assessing Gemcitabine/ Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer “Unfit” for Cisplatin-Based Chemotherapy: Phase II—Results of EORTC Study 30986

    PubMed Central

    De Santis, Maria; Bellmunt, Joaquim; Mead, Graham; Kerst, J. Martijn; Leahy, Michael; Maroto, Pablo; Skoneczna, Iwona; Marreaud, Sandrine; de Wit, Ronald; Sylvester, Richard

    2009-01-01

    Purpose There is no standard treatment for patients with advanced urothelial cancer who are ineligible (“unfit”) for cisplatin-based chemotherapy (CHT). To compare the activity and safety of two CHT combinations in this patient group, a randomized phase II/III trial was conducted by the EORTC (European Organisation for Research and Treatment of Cancer). We report here the phase II results of the study. Patients and Methods CHT-naïve patients with measurable disease and impaired renal function (30 mL/min < glomerular filtration rate [GFR] < 60 mL/min) and/or performance status (PS) 2 were randomly assigned to receive either GC (gemcitabine 1,000 mg/m2 on days 1 and 8 and carboplatin area under the serum concentration-time curve [AUC] 4.5) for 21 days or M-CAVI (methotrexate 30 mg/m2 on days 1, 15, and 22; carboplatin AUC 4.5 on day 1; and vinblastine 3 mg/m2 on days 1, 15, and 22) for 28 days. End points of response and severe acute toxicity (SAT) were evaluated with respect to treatment group, renal function, PS, and Bajorin risk groups. Results Three of 178 patients who were ineligible or did not start treatment were excluded. SAT was reported in 13.6% of patients on GC and in 23% on M-CAVI. Overall response rates were 42% (37 of 88) for GC and 30% (26 of 87) for M-CAVI. Patients with PS 2 and GFR less than 60 mL/min and patients in Bajorin risk group 2 showed a response rate of only 26% and 20% and an SAT rate of 26% and 25%, respectively. Conclusion Both combinations are active in this group of unfit patients. However, patients with PS 2 and GFR less than 60 mL/min do not benefit from combination CHT. Alternative treatment modalities should be sought in this subgroup of poor-risk patients. PMID:19786668

  3. Determination of As(III) and As(V) species in some natural water and food samples by solid-phase extraction on Streptococcus pyogenes immobilized on Sepabeads SP 70 and hydride generation atomic absorption spectrometry.

    PubMed

    Uluozlu, Ozgur Dogan; Tuzen, Mustafa; Mendil, Durali; Soylak, Mustafa

    2010-05-01

    The speciation of arsenic(III) and arsenic(V) by using Streptococcus pyogenes immobilized on Sepabeads SP 70 resin has been investigated with solid-phase extraction method. The arsenic levels were determined hydride generation atomic absorption spectrometry (HGAAS) in sample solutions. The procedure presented based on quantitative recoveries of As(III) as >95%. Also the As(V) recoveries were obtained as <5% using the presented method. After reduction of As(V) by using KI and ascorbic acid and waiting 1h later, the system was applied to determination of total arsenic. As(V) was found as the difference between the total As and As(III) content. Various experimental parameters such as pH, amount of microorganism, sample volume, etc. were investigated. The capacity of biosorbent for arsenic(III) was calculated as 7.3 mg/g. The preconcentration factor was found as 36. The relative standard deviation was calculated below 8%. Limit of detection was calculated as 13 ng/L. The validation of the presented procedure was tested by analysis of standard reference materials (NIST SRM 1568a Rice floor and GBW 07605 Tea) and obtained fairly compatible results. The procedure was also successfully applied to arsenic speciation and determination of some natural water and food samples.

  4. Pseudo Class III malocclusion

    PubMed Central

    Al-Hummayani, Fadia M.

    2016-01-01

    The treatment of deep anterior crossbite is technically challenging due to the difficulty of placing traditional brackets with fixed appliances. This case report represents a none traditional treatment modality to treat deep anterior crossbite in an adult pseudo class III malocclusion complicated by severely retruded, supraerupted upper and lower incisors. Treatment was carried out in 2 phases. Phase I treatment was performed by removable appliance “modified Hawley appliance with inverted labial bow,” some modifications were carried out to it to suit the presented case. Positive overbite and overjet was accomplished in one month, in this phase with minimal forces exerted on the lower incisors. Whereas, phase II treatment was performed with fixed appliances (braces) to align teeth and have proper over bite and overjet and to close posterior open bite, this phase was accomplished within 11 month. PMID:27052290

  5. Sb(III) and Sb(V) Sorption onto Al-Rich Phases: Hydrous Al Oxide and the Clay Minerals Kaolinite KGa-1b and Oxidized and Reduced Nontronite NAu-1

    SciTech Connect

    Ilgen, Anastasia G.; Trainor, Thomas P.

    2012-11-13

    We have studied the immobilization of Sb(III) and Sb(V) by Al-rich phases - hydrous Al oxide (HAO), kaolinite (KGa-1b), and oxidized and reduced nontronite (NAu-1) - using batch experiments to determine the uptake capacity and the kinetics of adsorption and Extended X-ray Absorption Fine Structure (EXAFS) Spectroscopy to characterize the molecular environment of adsorbed Sb. Both Sb(III) and Sb(V) are adsorbed in an inner-sphere mode on the surfaces of the studied substrates. The observed adsorption geometry is mostly bidentate corner-sharing, with some monodentate complexes. The kinetics of adsorption is relatively slow (on the order of days), and equilibrium adsorption isotherms are best fit using the Freundlich model. The oxidation state of the structural Fe within nontronite affects the adsorption capacity: if the clay is reduced, the adsorption capacity of Sb(III) is slightly decreased, while Sb(V) uptake is increased significantly. This may be a result of the presence of dissolved Fe(II) in the reduced nontronite suspensions or associated with the structural rearrangements in nontronite due to reduction. These research findings indicate that Sb can be effectively immobilized by Al-rich phases. The increase in Sb(V) uptake in response to reducing structural Fe in clay can be important in natural settings since Fe-rich clays commonly go through oxidation-reduction cycles in response to changing redox conditions.

  6. Welding III.

    ERIC Educational Resources Information Center

    Allegheny County Community Coll., Pittsburgh, PA.

    Instructional objectives and performance requirements are outlined in this course guide for Welding III, an advanced course in arc welding offered at the Community College of Allegheny County to provide students with the proficiency necessary for industrial certification. The course objectives, which are outlined first, specify that students will…

  7. Fe-15Ni-13Cr austenitic stainless steels for fission and fusion reactor applications - Part III: Phase stability during heavy ion irradiation

    NASA Astrophysics Data System (ADS)

    Lee, E. H.; Mansur, L. K.

    2000-01-01

    The phase stability in Fe-15Ni-13Cr alloys was investigated as a function of minor alloying additions after 4 MeV Ni ion irradiation at 948 K. The results showed that the stability of precipitate phases was dictated mainly by the defects produced by radiation damage and preferential segregation of Si and Ni at defects. In addition, radiation enhanced diffusion and cascade induced dissolution and mixing allowed kinetically sluggish phases to form rapidly under irradiation. These radiation effects caused an enhancement, retardation, or modification of thermal phases, and formation of new phases. The relative stability of precipitate phases varied sensitively with alloy composition. The roles of each alloying element on phase stability and the impact of radiation on the mechanisms of phase evolution were systematically studied and documented. The knowledge obtained from this work provides guidelines for designing alloys that lead to develop desired precipitate microstructures under irradiation.

  8. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  9. Ultrasensitive solution-phase electrochemical molecular beacon-based DNA detection with signal amplification by exonuclease III-assisted target recycling.

    PubMed

    Xuan, Feng; Luo, Xiaoteng; Hsing, I-Ming

    2012-06-19

    Taking advantage of the preferential exodeoxyribonuclease activity of exonuclease III in combination with the difference in diffusivity between an oligonucleotide and a mononucleotide toward a negatively charged ITO electrode, a highly sensitive and selective electrochemical molecular beacon (eMB)-based DNA sensor has been developed. This sensor realizes electrochemical detection of DNA in a homogeneous solution, with sensing signals amplified by an exonuclease III-based target recycling strategy. A hairpin-shaped oligonucleotide containing the target DNA recognition sequence, with a methylene blue tag close to the 3' terminus, is designed as the signaling probe. Hybridization with the target DNA transforms the probe's exonuclease III-inactive protruding 3' terminus into an exonuclease III-active blunt end, triggering the digestion of the probe into mononucleotides including a methylene blue-labeled electro-active mononucleotide (eNT). The released eNT, due to its less negative charge and small size, diffuses easily to the negative ITO electrode, resulting in an increased electrochemical signal. Meanwhile, the intact target DNA returns freely to the solution and hybridizes with other probes, releasing multiple eNTs and thereby further amplifies the electrochemical signal. This new immobilization-free, signal-amplified electrochemical DNA detection strategy shows great potential to be integrated in portable and cost-effective DNA sensing devices.

  10. Ultrasound assisted-deep eutectic solvent based on emulsification liquid phase microextraction combined with microsample injection flame atomic absorption spectrometry for valence speciation of chromium(III/VI) in environmental samples.

    PubMed

    Yilmaz, Erkan; Soylak, Mustafa

    2016-11-01

    A new type of deep eutectic solvents (DESs) have been prepared and used as extraction solvents for ultrasound assisted-deep eutectic solvent based emulsification liquid phase microextraction method (UA-DES-ELPME) for the determination and speciation of total chromium, chromium(III) and chromium(VI). The chromium concentration in DES rich phase (extraction phase) was determined by using microsample injection flame atomic absorption spectrometer (FAAS). The detection limit (LOD), the quantification limit (LOQ), preconcentration factor and relative standard deviation were found as 5.5µgL(-1), 18.2µgL(-1), 20 and 6%, respectively. The accuracy of the developed method was evaluated by the analysis of water the certified reference materials (TMDA-53.3 Fortified environmental water and TMDA-54.4 Fortified Lake Water) and addition-recovery tests for water samples. PMID:27591663

  11. A new method for separation and determination of Cr(III) and Cr(VI) in water samples by high-performance liquid chromatography based on anion exchange stationary phase of ionic liquid modified silica.

    PubMed

    Sadeghi, Susan; Moghaddam, Ali Zeraatkar

    2015-12-01

    In this work, N-methylimidazolium-chloride ionic liquid functionalized silica was prepared and used as an anion-exchange stationary phase for separation of chromium species by high-performance liquid chromatography (HPLC) with UV detection at 200 nm. The Cr(VI) as HCr2O7(-) and chelated Cr(III) with potassium hydrogen phthalate (PHP) as Cr(PHP)2 (-) was retained on the prepared column and separated using a mobile phase composed of 5% methanol in 25 mM phosphate buffer at pH 6.5. Several variables affecting the chelation/separation steps were modeled by response surface methodology (RSM) using Box-Behnken (BBD) design. The significance of the independent variables and their interactions were tested by the analysis of variances (ANOVA) with 95% confidence limit. Under the optimized conditions, the Cr(III) and Cr(VI) anionic species were well separated with a single peak for each Cr species at retention times of 2.3 and 4.3 min, respectively. The relationship between the peak area and concentration was linear in the range of 0.025-30 for Cr(III) and 0.5-20 mg L(-1) for Cr(VI) with detection limits of 0.010 and 0.210 mg L(-1) for Cr(III) and Cr(VI), respectively. The proposed method was validated by simultaneous separation and determination of the Cr species in tap and underground water samples without impose to any pretreatment. PMID:26526699

  12. Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

    SciTech Connect

    Kim, Tae Hyun; Park, Sook Ryun; Ryu, Keun Won; Kim, Young-Woo; Bae, Jae-Moon; Lee, Jun Ho; Choi, Il Ju; Kim, Yeon-Joo; Kim, Dae Yong

    2012-12-01

    Purpose: To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. Methods and Materials: The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Results: Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). Conclusions: Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.

  13. A Research Project to Determine the Student Acceptability and Learning Effectiveness of Microform Collections in Community Junior Colleges: Phase III. Final Report.

    ERIC Educational Resources Information Center

    Gaddy, Dale

    The American Association of Community and Junior Colleges launched the Microform Project in 1969 under a contract with the U.S. Office of Education. The major product of Phase I (1969-1970) was a bibliography of resource materials used in 10 courses of study at community colleges (see ED 040 708). During Phase II (1970-1971), a series of pilot…

  14. Carrier concentration and mobility in two-phase eutectic A/sup III/B/sup V/-Ge(Si) alloys

    SciTech Connect

    Leonov, V.V.

    1988-06-01

    The authors proposes a technique of determining the carrier concentration and mobility in the separate phases of two-phase alloys in which oriented rod-like inclusions have carrier concentrations similar to the host material. The calculations are then used to determine the carrier concentration and mobility in each alloy phase, and to discuss the doping processes and mechanisms of impurity incorporation in two-phase semiconductors. He studied the Hall constant R in two-phase, oriented eutectic alloys of InSb-Ge, InAs-Ge, GaAs-Ge, and GaAs-Si. He established that R depends on the relative orientations of the current flow, magnetic field, and elongated inclusions. Furthermore, the particular impurity concentration in the alloy also has an effect on R.

  15. Speciation of As(III) and As(V) in water samples by graphite furnace atomic absorption spectrometry after solid phase extraction combined with dispersive liquid-liquid microextraction based on the solidification of floating organic drop.

    PubMed

    Shamsipur, Mojtaba; Fattahi, Nazir; Assadi, Yaghoub; Sadeghi, Marzieh; Sharafi, Kiomars

    2014-12-01

    A solid phase extraction (SPE) coupled with dispersive liquid-liquid microextraction based on the solidification of floating organic drop (DLLME-SFO) method, using diethyldithiphosphate (DDTP) as a proper chelating agent, has been developed as an ultra preconcentration technique for the determination of inorganic arsenic in water samples prior to graphite furnace atomic absorption spectrometry (GFAAS). Variables affecting the performance of both steps were thoroughly investigated. Under optimized conditions, 100mL of As(ΙΙΙ) solution was first concentrated using a solid phase sorbent. The extract was collected in 2.0 mL of acetone and 60.0 µL of 1-undecanol was added into the collecting solvent. The mixture was then injected rapidly into 5.0 mL of pure water for further DLLME-SFO. Total inorganic As(III, V) was extracted similarly after reduction of As(V) to As(III) with potassium iodide and sodium thiosulfate and As(V) concentration was calculated by difference. A mixture of Pd(NO3)2 and Mg(NO3)2 was used as a chemical modifier in GFAAS. The analytical characteristics of the method were determined. The calibration graph was linear in the rage of 10-100 ng L(-1) with detection limit of 2.5 ng L(-1). Repeatability (intra-day) and reproducibility (inter-day) of method based on seven replicate measurements of 80 ng L(-1) of As(ΙΙΙ) were 6.8% and 7.5%, respectively. The method was successfully applied to speciation of As(III), As(V) and determination of the total amount of As in water samples and in a certified reference material (NIST RSM 1643e). PMID:25159375

  16. Structure of the CFA/III major pilin subunit CofA from human enterotoxigenic Escherichia coli determined at 0.90 Å resolution by sulfur-SAD phasing.

    PubMed

    Fukakusa, Shunsuke; Kawahara, Kazuki; Nakamura, Shota; Iwashita, Takaki; Baba, Seiki; Nishimura, Mitsuhiro; Kobayashi, Yuji; Honda, Takeshi; Iida, Tetsuya; Taniguchi, Tooru; Ohkubo, Tadayasu

    2012-10-01

    CofA, a major pilin subunit of colonization factor antigen III (CFA/III), forms pili that mediate small-intestinal colonization by enterotoxigenic Escherichia coli (ETEC). In this study, the crystal structure of an N-terminally truncated version of CofA was determined by single-wavelength anomalous diffraction (SAD) phasing using five sulfurs in the protein. Given the counterbalance between anomalous signal strength and the undesired X-ray absorption of the solvent, diffraction data were collected at 1.5 Å resolution using synchrotron radiation. These data were sufficient to elucidate the sulfur substructure at 1.38 Å resolution. The low solvent content (29%) of the crystal necessitated that density modification be performed with an additional 0.9 Å resolution data set to reduce the phase error caused by the small sulfur anomalous signal. The CofA structure showed the αβ-fold typical of type IVb pilins and showed high structural homology to that of TcpA for toxin-coregulated pili of Vibrio cholerae, including spatial distribution of key residues critical for pilin self-assembly. A pilus-filament model of CofA was built by computational docking and molecular-dynamics simulation using the previously reported filament model of TcpA as a structural template. This model revealed that the CofA filament surface was highly negatively charged and that a 23-residue-long loop between the α1 and α2 helices filled the gap between the pilin subunits. These characteristics could provide a unique binding epitope for the CFA/III pili of ETEC compared with other type IVb pili. PMID:22993096

  17. Speciation of As(III) and As(V) in water samples by graphite furnace atomic absorption spectrometry after solid phase extraction combined with dispersive liquid-liquid microextraction based on the solidification of floating organic drop.

    PubMed

    Shamsipur, Mojtaba; Fattahi, Nazir; Assadi, Yaghoub; Sadeghi, Marzieh; Sharafi, Kiomars

    2014-12-01

    A solid phase extraction (SPE) coupled with dispersive liquid-liquid microextraction based on the solidification of floating organic drop (DLLME-SFO) method, using diethyldithiphosphate (DDTP) as a proper chelating agent, has been developed as an ultra preconcentration technique for the determination of inorganic arsenic in water samples prior to graphite furnace atomic absorption spectrometry (GFAAS). Variables affecting the performance of both steps were thoroughly investigated. Under optimized conditions, 100mL of As(ΙΙΙ) solution was first concentrated using a solid phase sorbent. The extract was collected in 2.0 mL of acetone and 60.0 µL of 1-undecanol was added into the collecting solvent. The mixture was then injected rapidly into 5.0 mL of pure water for further DLLME-SFO. Total inorganic As(III, V) was extracted similarly after reduction of As(V) to As(III) with potassium iodide and sodium thiosulfate and As(V) concentration was calculated by difference. A mixture of Pd(NO3)2 and Mg(NO3)2 was used as a chemical modifier in GFAAS. The analytical characteristics of the method were determined. The calibration graph was linear in the rage of 10-100 ng L(-1) with detection limit of 2.5 ng L(-1). Repeatability (intra-day) and reproducibility (inter-day) of method based on seven replicate measurements of 80 ng L(-1) of As(ΙΙΙ) were 6.8% and 7.5%, respectively. The method was successfully applied to speciation of As(III), As(V) and determination of the total amount of As in water samples and in a certified reference material (NIST RSM 1643e).

  18. Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy With Bi-Weekly Docetaxel and Carboplatin for Stage III Unresectable, Non-Small-Cell Lung Cancer: Clinical Application of a Protocol Used in a Previous Phase II Study

    SciTech Connect

    Saitoh, Jun-Ichi; Saito, Yoshihiro; Kazumoto, Tomoko; Kudo, Shigehiro; Yoshida, Daisaku; Ichikawa, Akihiro; Sakai, Hiroshi; Kurimoto, Futoshi; Kato, Shingo; Shibuya, Kei

    2012-04-01

    Purpose: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). Methods and Materials: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m{sup 2}, and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. Results: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade {>=}3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade {>=}3 severity were observed in 2.6% and 1.7% of patients, respectively. Conclusions: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

  19. Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase‐4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24‐week multicentre, randomized, double‐blind, placebo‐controlled phase III trial

    PubMed Central

    Hong, S.; Park, C.‐Y.; Han, K. A.; Chung, C. H.; Ku, B. J.; Jang, H. C.; Ahn, C. W.; Lee, M.‐K.; Moon, M. K.; Son, H. S.; Lee, C. B.; Cho, Y.‐W.

    2016-01-01

    We assessed the 24‐week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase‐4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were −0.94% [least‐squares (LS) mean −1.22, −0.65] and −1.21 mmol/l (−1.72, −0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo‐controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM. PMID:26749529

  20. The peats of Costa Rica

    SciTech Connect

    Obando A, L.; Malavassi R, L.; Ramirez E, O. ); Cohen, A. . Dept. of Geological Sciences); Raymond, R. Jr.; Thayer, G.R. )

    1991-04-01

    The objectives of this investigation were: (1) to locate potential peat deposits in Costa Rica; (2) to estimate as closely as possible by representative sampling the amount of peat present in each deposit, and (3) to make a preliminary evaluation of the quality of the peat in each deposit. With information from soil maps and a 3-week survey of Costa Rica, it is estimated that a potential area of about 1000 km{sup 2} is covered by peat. Most of the peat area (about 830 km{sup 2}) is in northeastern Costa Rica in the Tortuguero area. An aerial survey identified the potential peat areas by the exclusive presence of the Yolillo palm. The next largest potential area of peat (about 175 km{sup 2}) is in the cloud-covered areas of the Talamanca Mountains. Some reconnaissance has been done in the Talamanca Mountains, and samples of the peat indicate that it is very similar to the sphagnum peat moss found in Canada and the northern US. Smaller bogs have been discovered at Medio Queso, El Cairo, Moin, and the Limon airport. Two bogs of immediate interest are Medio Queso and El Cairo. The Medio Queso bog has been extensively sampled and contains about 182,000 metric tons (dry) of highly decomposed peat, which is being used as a carrier for nitrogen-fixing bacteria. The El Cairo bog is sparsely sampled and contains about 1,300,000 metric tons of slightly decomposed dry peat. Plans are to use this peat in horticultural applications on nearby farms. 10 refs., 11 figs., 7 tabs.

  1. A phase III randomized trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) versus cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) in patients with metastatic breast cancer.

    PubMed

    Alonso, M C; Tabernero, J M; Ojeda, B; Llanos, M; Solà, C; Climent, M A; Seguí, M A; López, J J

    1995-04-01

    One hundred patients with metastatic breast cancer were randomly selected to receive combined chemotherapy treatment with adriamycin (50 mg/m2) or mitoxantrone (12 mg/m2) associated with 5-fluorouracil (600 mg/m2) and cyclophosphamide (600 mg/m2) administered intravenously every 21 days with a maximum of ten cycles. All patients included in this study were under 75 years of age and had ECOG performance status of less than 4. They had not been treated previously with chemotherapy for metastatic disease. Patients treated with adjuvant chemotherapy, which could not have included anthracyclines, had to have relapsed at least 12 months after the completion of therapy. There were no statistically significant differences in pretreatment characteristics or metastatic disease location between the two groups. Ninety-four patients were assessable for response. No differences were observed in response rate or in survival between the groups. The response rate (complete response (CR) and partial response (PR)) was 68% (13% CR and 55% PR for CAF; 0% CR and 68% PR for CNF). Median survival for all patients was 19 months (18 months with CAF and 19 months with CNF). All patients were assessable for toxicity. There were no differences in gastrointestinal and cardiac toxicity. More grade I-II hematologic toxicity episodes (p < 0.001) and treatment delays (p = 0.05) due to leucopenia were observed with the CNF group, and more grade III alopecia (p < 0.001) was observed with the CAF group. Patients received further therapeutic manoeuvres after finishing the study with a sequential treatment consisting of hormonal therapy and chemotherapy with mitomycin (M) -vinblastine (Vbl) (M 10 mg/m2 day 1, Vbl 5 mg/m2 days 1, 15 and 29; maximum 5 cycles). This chemotherapy treatment was received by 32 patients, with a response rate of 34% and grade III-IV hematologic toxicity of 37%. Treatment with CNF can be considered a good alternative to CAF for first-line treatment of metastatic breast cancer

  2. Reversed-phase ion-pair liquid chromatographic method for determination of reaction equilibria involving ionic species: exemplification of the method using ligand substitution reactions of ethylenediaminetetraacetatochromium(III) ion with acetate and phosphate ions.

    PubMed

    Sato, Emiko; Miya, Seiko; Saitoh, Kazunori; Saito, Shingo; Shibukawa, Masami

    2011-02-18

    A reversed-phase ion-pair liquid chromatographic method is presented for the determination of reaction equilibria involving ionic species of the same charge sign as reactant and product compounds. It has been demonstrated that ion-exchange chromatography or reversed-phase ion-pair chromatography is a useful tool for the determination of equilibrium constants of chemical reactions involving ionic species such as metal complexation reactions. Previous work with these methods has been based on the assumption that the limiting retention factors of the reactant and product species are constant independent of concentration of the chemical species (X) in the mobile phase, which reacts with the analyte compound. However, when all the reactant and product species are ions of the same charge sign as that of the species X, it is virtually impossible to apply these methods to the equilibrium constant determination because the retention factors of both the reactant and product species may depend on the concentration of X. In this study, an alternative approach was developed that estimates the limiting retention factors of ionic species from the dependence of the retention factor on the ionic strength of the mobile phase. Ligand substitution reactions of ethylenediaminetetraacetatochromium(III) ion with acetate and phosphate ions were used as model reactions to test this method. The equilibrium constants determined by this method are in good agreement with those obtained by a UV-visible spectrophotometric method.

  3. Prevalence of symptoms of asthma, rhinitis and eczema in 13- to 14-year-old children in Africa: the International Study of Asthma and Allergies in Childhood Phase III.

    PubMed

    Ait-Khaled, N; Odhiambo, J; Pearce, N; Adjoh, K S; Maesano, I A; Benhabyles, B; Bouhayad, Z; Bahati, E; Camara, L; Catteau, C; El Sony, A; Esamai, F O; Hypolite, I E; Melaku, K; Musa, O A; Ng'ang'a, L; Onadeko, B O; Saad, O; Jerray, M; Kayembe, J M; Koffi, N B; Khaldi, F; Kuaban, C; Voyi, K; M'Boussa, J; Sow, O; Tidjani, O; Zar, H J

    2007-03-01

    Phase I of the International Study of Asthma and Allergies in Childhood has provided valuable information regarding international prevalence patterns and potential risk factors in the development of asthma, allergic rhinoconjunctivitis and eczema. However, in Phase I, only six African countries were involved (Algeria, Tunisia, Morocco, Kenya, South Africa and Ethiopia). Phase III, conducted 5-6 years later, enrolled 22 centres in 16 countries including the majority of the centres involved in Phase I and new centres in Morocco, Tunisia, Democratic Republic of Congo, Togo, Sudan, Cameroon, Gabon, Reunion Island and South Africa. There were considerable variations between the various centres of Africa in the prevalence of the main symptoms of the three conditions: wheeze (4.0-21.5%), allergic rhinoconjunctivitis (7.2-27.3%) and eczema (4.7-23.0%). There was a large variation both between countries and between centres in the same country. Several centres, including Cape Town (20.3%), Polokwane (18.0%), Reunion Island (21.5%), Brazzaville (19.9%), Nairobi (18.0%), Urban Ivory Coast (19.3%) and Conakry (18.6%) showed relatively high asthma symptom prevalences, similar to those in western Europe. There were also a number of centres showing high symptom prevalences for allergic rhinoconjunctivitis (Cape Town, Reunion Island, Brazzaville, Eldoret, Urban Ivory Coast, Conakry, Casablanca, Wilays of Algiers, Sousse and Eldoret) and eczema (Brazzaville, Eldoret, Addis Ababa, Urban Ivory Coast, Conakry, Marrakech and Casablanca).

  4. Vegetation and climate history of montane Costa Rica since the last glacial

    NASA Astrophysics Data System (ADS)

    Islebe, G. A.; Hooghiemstra, H.

    New palynological evidence from the Cordillera de Talamanca (Costa Rica) is presented. The La Chonta-1 core (2310 m a.s.l) shows the development of montane vegetation during the late Quaternary. A shorter core (La Trinidad-III) shows the Lateglacial-Holocene transition, including the La Chonta stadial based on earlier published evidence. A soil section from the paramó belt at 3100 m shows vegetation recovery after fire. Modern pollen rain was studied along an altitudinal transect from 2100 m to 3800 m at Mt Chirripó. A comparison with other palaeoecological data of the region is given to elucidate climatic and vegetational changes throughout the Central American region. Data show a cooling of 7-8°C during the Last Glacial Maximum (LGM) for montane Costa Rica, which is in accordance with data from lowland Guatemala. A 1.5° to 2.5°C temperature drop is recorded during the Younger Dryas Chron in both Costa Rica and Guatemala, but apparently not in Panama. The Lateglacial-Holocene transition in montane Costa Rica is established at 10,400 BP. Between 9000 and 8500 BP moist forest developed in mountainous Costa Rica as well as in lowland Guatemala and Panama. Environmental change during the mid-Holocene seems more affected by changes in humidity than temperature change throughout Central America. Distribution maps of paramó and montane vegetation in Costa Rica are reconstructed for 10 ka, 14 ka and 18 ka based on currently available palynological data. These data indicate that during the LGM a paramó vegetation corridor existed between northern Costa Rica and probably northern Panama.

  5. A phase I/II trial of irinotecan-cisplatin combined with an anti-late-diarrhoeal programme to evaluate the safety and antitumour response of this combination therapy in patients with advanced non-small-cell lung cancer.

    PubMed

    Takeda, Y; Tsuduki, E; Izumi, S; Hojo, M; Kamimura, M; Naka, G; Kobayashi, K; Kudo, K

    2005-12-12

    We conducted a phase I/II study in patients with advanced non-small-cell lung cancer (NSCLC) to increase the therapeutic index of the cisplatin-irinotecan combination by institution of an anti-late-diarrhoeal program (ADP). A total of 77 chemotherapy-naive patients with advanced NSCLC were enrolled. The cisplatin dose was fixed at 60 mg m(-2) (Day 1). Irinotecan was escalated in 5 mg m(-2) increments, starting from 60 mg m(-2) (Days 1 and 8). ADP consisted of oral sodium bicarbonate, magnesium oxide, basic water, and ursodeoxycholic acid, and was administered orally for 4 days with each dose of irinotecan. In the phase I portion, irinotecan pharmacokinetics was also examined. After the recommended dose of irinotecan with ADP was determined, a phase II study was conducted to evaluate the response. Maximum tolerated dose was reached at an irinotecan dose of 80 mg m(-2) (Grade 4 diarrhoea and neutropenia). Pharmacokinetic studies show that the maximum concentration and the area under the curve of both irinotecan and SN38 (active metabolite of irinotecan) tend to increase in the dose-dependent manner of irinotecan. The phase II portion of the study included 48 patients, who were treated with 75 mg m(-2) of irinotecan. Grade 3/4 toxicities included neutropenia in 65%, leucopenia in 33%, and late diarrhoea in 6% of the patients. During this treatment, PS did not change in 65% of patients. At the end of the chemotherapy, PS did not decline in 90% of patients. In the phase II portion, a response occurred in 63% (95% confidential interval (CI), 47-76%) of patients. Median time to progression was 19 weeks (95% CI, 15-22 weeks), and median survival was 52 weeks (95% CI, 39-64 weeks). This regimen of irinotecan and cisplatin with ADP resulted in promising efficacy with acceptable toxicity for patients with advanced NSCLC. This regimen is a candidate for the experimental arm towards future phase III studies. PMID:16288302

  6. A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas

    PubMed Central

    Jones, Robin L.; Rossen, Philip Blach; Lind-Hansen, Maja; Knoblauch, Poul

    2016-01-01

    Background. Belinostat is a novel histone deacetylase inhibitor. Primary Objectives. Maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of belinostat (Bel) in combination with doxorubicin (Dox) in solid tumours (phase I) and response rate (RR) in soft tissue sarcomas (phase II). Methods. Bel was administered as a 30-minute IV infusion on days 1–5 and on day 5 with Dox. The dose escalation schedule was as follows: cohort 1: Bel 600 mg/m2 and 50 mg/m2 Dox, cohort 2: Bel 600 mg/m2 and 75 mg/m2 Dox, cohort 3: Bel 800 mg/m2 and 75 mg/m2 Dox, and cohort 4: Bel 1000 mg/m2 and 75 mg/m2 Dox. Results. 41 patients were included (25 in phase I, 16 in phase II). Adverse events were fatigue (95%), nausea (76%), and alopecia (63%). There was one DLT, grade 3 rash/hand and foot syndrome. MTD was Bel 1000 mg/m2/d and Dox 75 mg/m2. Four responses were seen: 2 PR in phase I, RR of 8%; in phase II, 1 PR/1 CR, RR of 13%, and 9 patients (56%) with SD. Conclusion. The combination was well tolerated. Response rate was moderate but median time to progression was 6.0 months (95% CI, 1.6–9.7 months) which is superior to some reports of single-agent Dox. PMID:27403082

  7. Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis

    PubMed Central

    Dirschka, T; Radny, P; Dominicus, R; Mensing, H; Brüning, H; Jenne, L; Karl, L; Sebastian, M; Oster-Schmidt, C; Klövekorn, W; Reinhold, U; Tanner, M; Gröne, D; Deichmann, M; Simon, M; Hübinger, F; Hofbauer, G; Krähn-Senftleben, G; Borrosch, F; Reich, K; Berking, C; Wolf, P; Lehmann, P; Moers-Carpi, M; Hönigsmann, H; Wernicke-Panten, K; Hahn, S; Pabst, G; Voss, D; Foguet, M; Schmitz, B; Lübbert, H; Szeimies, R-M

    2013-01-01

    Background Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. Objectives To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo. Methods The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Results Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. Conclusions The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy. PMID:23252768

  8. Structures and phases transition in hexylenediammonium pentachlorobismuthate (III) [NH{sub 3}(CH{sub 2}){sub 6}NH{sub 3}]BiCl{sub 5} crystal

    SciTech Connect

    Ouasri, A.; Jeghnou, H.; Rhandour, A.; Roussel, P.

    2013-04-15

    The crystal structure of [NH{sub 3}(CH{sub 2}){sub 6}NH{sub 3}]BiCl{sub 5} was determined at: 223 K [P2{sub 1}2{sub 1}2{sub 1} (Z=4), a=7.788(1), b=13.886(2), c=13.972(2) Å], 308 K [P2{sub 1}/n (Z=8), a=19.972(3), b=7.772(2), c=20.166(3) Å, β=92.32(1)°] and 378 K [Pnma (Z=4), a=13911(2), b=7.834(7), c=14.457(2) Å]. It was consisted of isolated (BiCl{sub 5}{sup 2−}){sub n} anionic chains composed by distorted octahedra BiCl{sub 6}{sup 3−} sharing two corners and {sup +}NH{sub 3}(CH{sub 2}){sub 6}NH{sub 3}{sup +} cations placed in the free cavities between anionic chains. In the β phase, there are two crystallographically inequivalent cations and two one-dimensional anionic chains (BiCl{sub 5}{sup 2−}){sub n} in which BiCl{sub 6}{sup 3−} octahedra was doubly tilted and simply tilted. Two structural phase transitions at low and high temperatures α (P2{sub 1}2{sub 1}2{sub 1}, 223 K)↔β (P2{sub 1}/n, 308 K)↔γ (Pnma, 373 K) are observed and discussed. It was crystallographically showed that both anionic and cationic entities contribute to phase transitions mechanisms. The BiCl{sub 6}{sup 3−} octahedra were found to posses significant distortions on decreasing temperature and became more distorted in α (223 K) phase. It is argued that these deformations are caused by weak to moderate N--H···Cl hydrogen bonding. - Graphical abstract: Projection of the crystal structure of [NH{sub 3}(CH{sub 2}){sub 6}NH{sub 3}]BiCl{sub 5} down the a axis at 208 K. Highlights: ► The crystal shows two phase transitions: α(223 K)↔β(308 K)↔γ(373 K). ► A discontinuous transition may be occurred between α and β phases. ► The α↔β and β↔γ phase transitions are of first order. ► Both anionic and cationic motions contribute to phase transition mechanisms. ► The BiCl{sub 6}{sup 3−} octahedra showed significant distortions on decreasing temperature.

  9. Nanostructures produced by phase-separation during growth of (III-V).sub.1-x(IV.sub.2).sub.x alloys

    DOEpatents

    Norman, Andrew G.; Olson, Jerry M.

    2007-06-12

    Nanostructures (18) and methods for production thereof by phase separation during metal organic vapor-phase epitaxy (MOVPE). An embodiment of one of the methods may comprise providing a growth surface in a reaction chamber and introducing a first mixture of precursor materials into the reaction chamber to form a buffer layer (12) thereon. A second mixture of precursor materials may be provided into the reaction chamber to form an active region (14) on the buffer layer (12), wherein the nanostructure (18) is embedded in a matrix (16) in the active region (14). Additional steps are also disclosed for preparing the nanostructure (18) product for various applications.

  10. Facing AIDS in Costa Rica.

    PubMed

    Mata, L

    1988-03-01

    The 1st AIDS case was diagnosed in Costa Rica in 1985. By January 1988, 47 cases were recorded. Most cases are in hemophiliacs and homosexuals; one is in the heterosexual partner of a hemophiliac. 55% of hemophiliacs in Costa Rica are infected with HIV -- one of the highest levels in the world. 10 women, including 2 prostitutes, are known to be HIV-positive. The number of new cases is expected to nearly double every year, and deaths from AIDS may come to exceed deaths from diarrhea and all other infectious diseases. Since 1985, all donated blood has been screened. A national education campaign began in 1985, using television, talks, workshops, and pamphlets, and coordinated by the National AIDS Commission. AIDS education is included in secondary and high school curricula, and condoms have been distributed in gay discotheques and other public places since 1987. Failure to recognize the problem early enough resulted in fear of and discrimination against AIDS patients by health workers as well as failure to provide enough funds for AIDS prevention and control. PMID:12315654

  11. Mercury Contamination in Costa Rica

    NASA Astrophysics Data System (ADS)

    Varekamp, J. C.; Haynes, A.; Balcom, P. H.

    2012-12-01

    Recent measurements of Hg in air in the central valley of Costa Rica produced some remarkably high values (up to 700 ng Hg/m3;Castillo et al., 2011), raising concerns for public health. We made a broad assessment of Hg as an environmental contaminant in Costa Rica, and sampled and analyzed lake and wetland sediment and soils to derive atmospheric Hg deposition rates. We also measured Hg(0) in air in three locations, and sampled local fish that were analyzed for Hg. We set up a sampling program of Hg in hair of Costa Ricans, sampling hair from a broad crossection of the population, in combination with dietary and personal information. The lake sediments had Hg concentrations between 34 and 316 ppb Hg, with several lakes at common natural background concentrations (20-100 ppb Hg). Some lakes showed a Hg contamination component with concentrations well above simple background values. These sediments also were very rich in organic matter, and the high Hg concentrations may be a result of Hg focusing from the watersheds into the lake depositional environments. Deduced atmospheric deposition rates of Hg range from 0.16-0.25 ng Hg/cm2 per year, which is at the low end of the global range of measured wet atmospheric deposition rates. The observed Hg concentrations in sediment and soils thus can be characterized as natural background to mildly contaminated, but nothing that would indicate Hg inventories as expected from the reported high Hg air burdens. Some of our Hg(0) in air measurements were done at the same locations as those done earlier and yielded values between 0.6-4.2 ng Hg/m3; these values are similar to the low range measurements of Castillo et al. (their night time values), but we found no evidence in 2011 for their high daytime values. The range of a few ng Hg/m3 in air is compatible with global Hg dispersion modeling. Fish tissue of Trout and Tilapia gave a range of 68-112 ppb Hg (wet weight base), well below the 300 ppb Hg EPA alert level. Overall, these

  12. Autophagy Inhibition to Augment mTOR Inhibition: A Phase I/II Trial of RAD001 and Hydroxychloroquine in Patients With Previously Treated Renal Cell Carcinoma

    ClinicalTrials.gov

    2015-12-07

    Histological Evidence of Metastatic Clear Cell Renal Cell Carcinoma; That Has Been Previously Treated With 1-3 Prior Regimens. Phase 1 Only, Any Number of Prior Regimens; With Evidence of Progressive Disease on or Within 6 Months; of Discontinuing Sunitinib, Sorafenib or Pazopanib. Previous; Therapy With Bevacizumab, IL2, or Interferon Are Permitted.

  13. A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03

    PubMed Central

    Iwamoto, Fabio M.; Lamborn, Kathleen R.; Kuhn, John G.; Wen, Patrick Y.; Alfred Yung, W.K.; Gilbert, Mark R.; Chang, Susan M.; Lieberman, Frank S.; Prados, Michael D.; Fine, Howard A.

    2011-01-01

    Romidepsin, a potent histone deacetylase inhibitor, has shown activity in preclinical glioma models. The primary objectives of this trial were to determine the pharmacokinetics of romidepsin in patients with recurrent glioma on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of romidepsin in patients with recurrent glioblastoma who were not receiving EIAEDs. Two dose cohorts were studied in the phase I component of the trial (13.3 and 17.7 mg/m2/d). Patients in the phase II component were treated with intravenous romidepsin at a dosage of 13.3 mg/m2/day on days 1, 8, and 15 of each 28-day cycle. Eight patients were treated on the phase I component. A similar romidepsin pharmacokinetic profile was demonstrated between patients receiving EIAEDs to those not receving EIAEDs. Thirty-five patients with glioblastoma were accrued to the phase II component. There was no objective radiographic response. The median progression-free survival (PFS) was 8 weeks and only 1 patient had a PFS time ≥6 months (PFS6 = 3%). To date, 34 patients (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that romidepsin is primarily metabolized by CYP3A4, no decrease in exposure to romidepsin was seen in patients receiving potent CYP3A4 inducers. Romidepsin, at its standard dose and schedule, was ineffective for patients with recurrent glioblastomas. ClinicalTrials.gov identifier: NCT00085540. PMID:21377994

  14. A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03.

    PubMed

    Iwamoto, Fabio M; Lamborn, Kathleen R; Kuhn, John G; Wen, Patrick Y; Yung, W K Alfred; Gilbert, Mark R; Chang, Susan M; Lieberman, Frank S; Prados, Michael D; Fine, Howard A

    2011-05-01

    Romidepsin, a potent histone deacetylase inhibitor, has shown activity in preclinical glioma models. The primary objectives of this trial were to determine the pharmacokinetics of romidepsin in patients with recurrent glioma on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of romidepsin in patients with recurrent glioblastoma who were not receiving EIAEDs. Two dose cohorts were studied in the phase I component of the trial (13.3 and 17.7 mg/m(2)/d). Patients in the phase II component were treated with intravenous romidepsin at a dosage of 13.3 mg/m(2)/day on days 1, 8, and 15 of each 28-day cycle. Eight patients were treated on the phase I component. A similar romidepsin pharmacokinetic profile was demonstrated between patients receiving EIAEDs to those not receving EIAEDs. Thirty-five patients with glioblastoma were accrued to the phase II component. There was no objective radiographic response. The median progression-free survival (PFS) was 8 weeks and only 1 patient had a PFS time ≥6 months (PFS6 = 3%). To date, 34 patients (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that romidepsin is primarily metabolized by CYP3A4, no decrease in exposure to romidepsin was seen in patients receiving potent CYP3A4 inducers. Romidepsin, at its standard dose and schedule, was ineffective for patients with recurrent glioblastomas. ClinicalTrials.gov identifier: NCT00085540.

  15. Scattering Properties of Jovian Tropospheric Cloud Particles Inferred from Cassini/ISS: Mie Scattering Phase Function and Particle Size in South Tropical Zone III

    NASA Astrophysics Data System (ADS)

    Sato, T.; Satoh, T.; Kasaba, Y.

    2010-12-01

    The three distinct cloud layers were predicted by an equilibrium cloud condensation model (ECCM) of Jupiter. An ammonia ice cloud (NH3), an ammonia hydrosulfide cloud (NH4SH), and a water ice (H2O) cloud would be based at altitudes corresponding to pressures of about 0.7, 2.2 and 6 bars, respectively. However, there are significant gaps in our knowledge of the vertical cloud structure, despite the continuing effort by numerous ground-based, space-based, and in-situ observations and theory. Methane (CH4) is considered that its altitude distribution is globally uniform because it does not condense in Jovian atmosphere. Therefore, it is possible to derive the vertical cloud structure and the optical properties of clouds (i.e., optical thickness and single scattering albedo) by observing reflected sunlight in CH4 bands (727, 890 nm) and continuum in visible to near-infrared spectral ranges. Since we need to consider multiple scattering by clouds, it is essential to know scattering properties (e.g., scattering phase function) of clouds for determination of vertical cloud structure. However, we cannot derive those from ground-based and Earth-orbit observations because of the limitation of solar phase angle as viewed from the Earth. Then, most previous studies have used the scattering phase function deduced from the Pioneer 10/IPP data (blue: 440 nm, red: 640nm) [Tomasko et al., 1978]. There are two shortcomings in the Pioneer scattering phase function. One is that we have to use this scattering phase function at red as a substitute for analyses of imaging photometry using CH4 bands (center: 727 and 890 nm), although clouds should have wavelength dependency. The other is that the red pass band of IPP was so broad (595-720 nm) that this scattering phase function in red just show wavelength-averaged scattering properties of clouds. To provide a new reference scattering phase function with wavelength dependency, we have analyzed the Cassini/ISS data in BL1 (451 nm), CB1 (619

  16. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia

    PubMed Central

    2013-01-01

    Background Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. Methods Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. Results Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. Conclusion BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. Trial registration NIH website (http

  17. Reprint of: Multiwavelength modeling the SED of supersoft X-ray sources III. RS Ophiuchi: The supersoft X-ray phase and beyond

    NASA Astrophysics Data System (ADS)

    Skopal, A.

    2015-04-01

    I modeled the 14 Å-37 μ m SED of the recurrent symbiotic nova RS Oph during its supersoft source (SSS) phase and the following quiescent phase. During the SSS phase, the model SEDs revealed the presence of a strong stellar and nebular component of radiation in the spectrum. The former was emitted by the burning WD at highly super-Eddington rate, while the latter represented a fraction of its radiation reprocessed by the thermal nebula. During the transition phase, both the components were decreasing and during quiescence the SED satisfied radiation produced by a large, optically thick disk (Rdisk > 10 R⊙). The super-Eddington luminosity of the burning WD during the SSS phase was independently justified by the high quantity of the nebular emission. The emitting material surrounded the burning WD, and its mass was (1.6 ± 0.5) ×10-4(d / 1.6kpc) 5 / 2 M⊙ . The helium ash, deposited on the WD surface during the whole burning period, was around of 8 ×10-6(d / 1.6kpc) 2 M⊙ , which yields an average growing rate of the WD mass, M˙WD ∼ 4 ×10-7(d / 1.6kpc) 2 M⊙yr-1 . The mass accreted by the WD between outbursts, macc ∼ 1.26 ×10-5 M⊙ , constrains the average accretion rate, M˙acc ∼ 6.3 ×10-7 M⊙yr-1 . During quiescence, the accretion rate from the model SED of ∼ 2.3 ×10-7 M⊙yr-1 requires a super-Eddington accretion from the disk at ∼ 3.6 ×10-5 M⊙yr-1 during the outburst. Such a high accretion can be responsible for the super-Eddington luminosity during the whole burning phase. Simultaneous presence of jets supports this scenario. If the wind from the giant is not sufficient to feed the WD at the required rate, the accretion can be realized from the disk-like reservoir of material around the WD. In this case the time between outbursts will extend, with the next explosion beyond 2027. In the opposite case, the wind from the giant has to be focused to the orbital plane to sustain the high accretion rate at a few ×10-7 M⊙yr-1 . Then the

  18. Multiwavelength modeling the SED of supersoft X-ray sources III. RS Ophiuchi: The supersoft X-ray phase and beyond

    NASA Astrophysics Data System (ADS)

    Skopal, A.

    2015-01-01

    I modeled the 14 Å-37 μm SED of the recurrent symbiotic nova RS Oph during its supersoft source (SSS) phase and the following quiescent phase. During the SSS phase, the model SEDs revealed the presence of a strong stellar and nebular component of radiation in the spectrum. The former was emitted by the burning WD at highly super-Eddington rate, while the latter represented a fraction of its radiation reprocessed by the thermal nebula. During the transition phase, both the components were decreasing and during quiescence the SED satisfied radiation produced by a large, optically thick disk (Rdisk>10 R⊙). The super-Eddington luminosity of the burning WD during the SSS phase was independently justified by the high quantity of the nebular emission. The emitting material surrounded the burning WD, and its mass was (1.6±0.5)×10-4( M⊙. The helium ash, deposited on the WD surface during the whole burning period, was around of 8×10-6( M⊙, which yields an average growing rate of the WD mass, M˙WD∼4×10-7( M⊙ yr. The mass accreted by the WD between outbursts, macc∼1.26×10-5 M⊙, constrains the average accretion rate, M˙acc∼6.3×10-7 M⊙ yr. During quiescence, the accretion rate from the model SED of ∼2.3×10-7 M⊙ yr requires a super-Eddington accretion from the disk at ∼3.6×10-5 M⊙ yr during the outburst. Such a high accretion can be responsible for the super-Eddington luminosity during the whole burning phase. Simultaneous presence of jets supports this scenario. If the wind from the giant is not sufficient to feed the WD at the required rate, the accretion can be realized from the disk-like reservoir of material around the WD. In this case the time between outbursts will extend, with the next explosion beyond 2027. In the opposite case, the wind from the giant has to be focused to the orbital plane to sustain the high accretion rate at a few ×10-7 M⊙ yr. Then the next explosion can occur even prior to 2027.

  19. Solid phase extraction of gold(III) on silica gel modified with benzoylthiourea prior to its determination by flame atomic absorption spectrometry.

    PubMed

    Bozkurt, Serap Seyhan; Merdivan, Melek

    2009-11-01

    A new method has been developed for the determination of gold based on separation and preconcentration using silica gel modified with benzoylthiourea. The optimum experimental parameters for preconcentration of gold, such as acid concentration, sample flow rate, eluent and matrix ions, have been investigated. Gold could be quantitatively retained in the 0.25-2.0 mol L(-1) HCl and HNO(3) concentrations, and then eluted completely with 0.5 mol L(-1) thiourea in 1.0 mol L(-1) HCl. The sorption capacity of gold(III) is 0.92 +/- 0.04 mmol g(-1) with a high enrichment factor of 267. The relative standard deviation of the method, RSD%, was found as 1.2% for 0.1 microg mL(-1). The detection limit for gold was 1.4 microg L(-1). The validation of the proposed method was checked by the analysis of certified reference soil materials. The presented procedure was applied to the determination of gold in some environmental samples.

  20. Phase I/II Trial of the Pharmacokinetics, Safety, and Antiretroviral Activity of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Adults

    PubMed Central

    Barditch-Crovo, Patricia; Deeks, Steven G.; Collier, Ann; Safrin, Sharon; Coakley, Dion F.; Miller, Michael; Kearney, Brian P.; Coleman, Rebecca L.; Lamy, Patrick D.; Kahn, James O.; McGowan, Ian; Lietman, Paul S.

    2001-01-01

    Tenofovir DF is an antiviral nucleotide with activity against human immunodeficiency virus type 1 (HIV-1). The pharmacokinetics, safety, and activity of oral tenofovir DF in HIV-1-infected adults were evaluated in a randomized, double-blind, placebo-controlled, escalating-dose study of four doses (75, 150, 300, and 600 mg given once daily). Subjects received a single dose of tenofovir DF or a placebo, followed by a 7-day washout period. Thereafter, subjects received their assigned study drug once daily for 28 days. Pharmacokinetic parameters were dose proportional and demonstrated no change with repeated dosing. Reductions in plasma HIV-1 RNA were dose related at tenofovir DF doses of 75 to 300 mg, but there was no increase in virus suppression between the 300- and 600-mg dose cohorts, despite dose-proportional increases in drug exposure. Grade III or IV adverse events were limited to laboratory abnormalities, including elevated creatine phosphokinase and liver function tests, which resolved with or without drug discontinuation and without sequelae. No patients developed detectable sequence changes in the reverse transcriptase gene. PMID:11557462

  1. Concomitant Chemoradiotherapy With Mitomycin C and Cisplatin in Advanced Unresectable Carcinoma of the Head and Neck: Phase I-II Clinical Study

    SciTech Connect

    Strojan, Primoz Karner, Katarina; Smid, Lojze; Soba, Erika; Fajdiga, Igor; Jancar, Boris; Anicin, Aleksandar; Budihna, Marjan; Zakotnik, Branko

    2008-10-01

    Purpose: To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck. Patients and Methods: Treatment consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m{sup 2} IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m{sup 2}/d IV, applied during the last 10 fractions of irradiation ('chemoboost'). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m{sup 2}/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m{sup 2}/d (Phase I study), which was tested in the subsequent Phase II study. Results: All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m{sup 2}/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m{sup 2}/d, the corresponding rates were 40%, 20%, and 22%, respectively. Conclusion: Concomitant chemoradiotherapy with mitomycin C and cisplatin 'chemoboost' at 14 mg/m{sup 2}/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.

  2. Pressure, temperature and density drops along supercritical fluid chromatography columns in different thermal environments. III. Mixtures of carbon dioxide and methanol as the mobile phase.