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1. The Metal-Silicate Partitioning of Carbon During Earth's Accretion and its Distribution in the Early Solar System

Author

Blanchard, I., Rubie, D. C., Jennings, E. S., Franchi, I. A., Zhao, X., Petitgirard, S., Miyajima, N., Jacobson, S. A., and Morbidelli, A.

Subjects
Astrophysics - Earth and Planetary Astrophysics, Physics - Geophysics
Abstract

Carbon is an essential element for the existence and evolution of life on Earth. Its abundance in Earth's crust and mantle (the Bulk Silicate Earth, BSE) is surprisingly high given that carbon is strongly siderophile (metal-loving) at low pressures and temperatures, and hence should have segregated almost completely into Earth's core during accretion. Estimates of the concentration of carbon in the BSE lie in the range 100-260 ppm and are much higher than expected based on simple models of core-mantle differentiation. Here we show through experiments at the putative conditions of Earth's core formation (49-71 GPa and 3600-4000 K) that carbon is significantly less siderophile at these conditions than at the low pressures ($\leq$13 GPa) and temperatures ($\leq$2500 K) of previous large volume press studies, but at least an order of magnitude more siderophile than proposed recently based on an experimental approach that is similar to ours. Using our new data along with previously published results, we derive a new parameterization of the pressure-temperature dependence of the metal-silicate partitioning of carbon. We apply this parameterization in a model that combines planet formation and core-mantle differentiation that is based on astrophysical N-body accretion simulations. Because differentiated planetesimals were almost completely depleted in carbon due to sublimation at high temperatures, almost all carbon in the BSE was added by the accretion of fully-oxidized carbonaceous chondrite material from the outer solar system. Carbon is added to the mantle continuously throughout accretion and its concentration reaches values within the BSE range (e.g. 140$\pm$40 ppm) at the end of accretion. The corresponding final core and bulk Earth carbon concentrations are 1270$\pm$300 ppm and 495$\pm$125 ppm respectively., Comment: Supplementary material included in pdf

Published
2022
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5. Experimental calibration of a garnet-clinopyroxene geobarometer for mantle eclogites

Author

Beyer, C., Frost, D. J., and Miyajima, N.

Subjects
Thermodynamics, Rocks, Igneous -- Inclusions, Earth sciences
Abstract

Thermodynamic parameters have been calibrated for a geobarometer suitable for use on eclogitic mantle xenoliths. The barometer is based on the incorporation of tetrahedrally coordinated aluminum in clinopyroxene coexisting with garnet and has been calibrated using the results of piston cylinder and multi-anvil experiments performed between pressures of 3 and 7 GPa and temperatures from 1,200 to 1,550 °C. Starting materials were hydrous and anhydrous synthetic mixtures of basaltic bulk compositions that yielded homogeneous bimineralic garnet-clinopyroxene phase assemblages. The experimental data set was expanded by employing results from previous experimental studies conducted in eclogitic systems, which widened the range of applicable conditions and compositions. The calibration reproduces experimental pressures of bimineralic eclogite assemblages, in addition to SiO.sub.2-saturated and kyanite-bearing eclogites, to within 0.4 GPa at the 95 % confidence interval. The barometer was then used to examine equilibration pressures recorded by natural mantle eclogites from various xenolith locations covering a wide pressure, temperature, and compositional range. Electronic supplementary material The online version of this article (doi:10.1007/s00410-015-1113-z) contains supplementary material, which is available to authorized users., Author(s): C. Beyer[sup.1] , D. J. Frost[sup.1] , N. Miyajima[sup.1] Author Affiliations: (1) Bayerisches Geoinsitut, University of Bayreuth, 95440, Bayreuth, Germany Introduction Geobarometry measurements are essential for understanding the thickness, [...]

Published
2015
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9. The effect of aluminum and water on the development of deformation fabrics of orthopyroxene

Author

Manthilake, M.A.G.M., Miyajima, N., Heidelbach, F., Soustelle, V., and Frost, D.J.

Subjects
Anisotropy, Water, Aluminum oxide, Earth sciences
Abstract

The effect of alumina and water solubility on the development of fabric in orthopyroxene in response to simple shear deformation has been investigated at a pressure of 1.5 GPa and a temperature of 1,100 °C using the D-DIA apparatus. The microstructure observations at these conditions indicate that dislocation glide is the dominant deformation mechanism. In MgSi[O.sub.3] enstatite and hydrous aluminous enstatite, partial dislocations bounding the stacking faults in [001] glide parallel to the (100) (or) the (100) [001] slip system. Electron backscattered diffraction analysis of anhydrous aluminous enstatite, however, indicates operation of the (010) [001] slip system, and microstructure analysis indicates dislocation movement involving [001] on both (100) and {210} planes. The strong covalent bonding induced by the occupation of M1 and T2 sites by Al could have restricted the glide on (100), activating slip on {210}. The resulting seismic anisotropies (~2 %) in orthopyroxene are weaker compared to olivine (~9.5 %), and reduced anisotropy can be expected if orthopyroxene coexists with olivine. Weak anisotropy observed in stable cratonic regions can be explained by the relatively high abundance of orthopyroxene in these rocks. Keywords Aluminous enstatite * Deformation * Dislocation glide * Seismic anisotropy * VPSC modeling * J index, Introduction Pyroxenes are the second most abundant mineral phases in the upper mantle and are a major constituent of mafic and ultramafic rocks such as lherzolites and pyroxenites. It is [...]

Published
2013
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13. Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity

Author

Fujiwara, T, Ikeda, M, Esumi, K, Fujita, T D, Kono, M, Tokushige, H, Hatoyama, T, Maeda, T, Asai, T, Ogawa, T, Katsumata, T, Sasaki, S, Suzuki, E, Suzuki, M, Hino, F, Fujita, T K, Zaima, H, Shimada, M, Sugawara, T, Tsuzuki, Y, Hashimoto, Y, Hishigaki, H, Horimoto, S, Miyajima, N, Yamamoto, T, Imagawa, K, Sesoko, S, and Fujisawa, Y

Published
2007
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14. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

Author

Petrylak, D.P. de Wit, R. Chi, K.N. Drakaki, A. Sternberg, C.N. Nishiyama, H. Castellano, D. Hussain, S.A. Fléchon, A. Bamias, A. Yu, E.Y. van der Heijden, M.S. Matsubara, N. Alekseev, B. Necchi, A. Géczi, L. Ou, Y.-C. Coskun, H.S. Su, W.-P. Bedke, J. Gakis, G. Percent, I.J. Lee, J.-L. Tucci, M. Semenov, A. Laestadius, F. Peer, A. Tortora, G. Safina, S. Garcia del Muro, X. Rodriguez-Vida, A. Cicin, I. Harputluoglu, H. Tagawa, S.T. Vaishampayan, U. Aragon-Ching, J.B. Hamid, O. Liepa, A.M. Wijayawardana, S. Russo, F. Walgren, R.A. Zimmermann, A.H. Hozak, R.R. Bell-McGuinn, K.M. Powles, T. Wong, S.-L.S. Tan, T.H. Hovey, E.J. Clay, T.D. Wan Ng, S.S. Rutten, A. Machiels, J.-P. Dumez, H. Cheng, S.Y.-S. Ferrario, C. Sengeloev, L. Jensen, N.V. Thibault, C. Laguerre, B. Joly, F. Culine, S. Becht, C. Niegisch, G. Stöckle, M. Grimm, M.-O. Schwentner, C.A. Schultze-Seemann, W. Kalofonos, H. Mavroudis, D. Papandreou, C. Karavasilis, V. Révész, J. Rosenbaum, E. Leibowitz-Amit, R. Kejzman, D. Sarid, D. Scagliotti, G.V. Bracarda, S. Massari, F. Osawa, T. Miyajima, N. Shinohara, N. Fukuta, F. Ohyama, C. Obara, W. Yamashita, S. Tomita, Y. Kawai, K. Fukasawa, S. Oyama, M. Yonese, J. Nagata, M. Uemura, M. Nishimura, K. Kawakita, M. Tsunemori, H. Hashine, K. Inokuchi, J. Yokomizo, A. Nagamori, S. Lee, H.J. Park, S.H. Rha, S.Y. Kim, Y.J. Lee, Y.-G. Vazquez Cortés, L. Lorena Urzua Flores, C. Blaisse, R.J.B. Erdkamp, F.L.G. Aarts, M.J.B. Wojcik-Tomaszewska, J. Tomczak, P. Sikora-Kupis, B. Schenker, M. Herzal, A.A. Udrea, A.A. Karlov, P. Fomkin, R. Gajate Borau, P. Grande, E. Delgado Mignorance, J.I. Su, Y.-L. Li, J.-R. Lin, C.-L. Lin, C.-C. Yeh, S.-P. Erman, M. Urun, Y. Golovko, Y. Bondarenko, I. Sinielnikov, I. Crabb, S.J. Syndikus, I. Huddart, R. Sundar, S. Chowdhury, S. Sarwar, N. Flaig, T.W. Pan, C.X. Schwarz, J.K. Cultrera, J.L. Acs, P.I. Hainsworth, J.D. Herms, B.T. Lawler, W.E. Lowe, T.E.

Abstract

Background: Ramucirumab—an IgG1 vascular endothelial growth factor receptor 2 antagonist—plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5–13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3–4·8] vs 2·8 months [2·6–2·9]; HR 0·696 [95% CI 0·573–0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9–11·4) in the ramucirumab group versus 7·9 months (7·0–9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724–1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Funding: Eli Lilly and Company. © 2020 Elsevier Ltd

Published
2020

21. Erratum to: Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma

Author

Abe, T, primary, Minami, K, primary, Harabayashi, T, primary, Sazawa, A, primary, Chiba, H, primary, Kikuchi, H, primary, Miyata, H, primary, Matsumoto, R, primary, Osawa, T, primary, Maruyama, S, primary, IshizakiIshizaki, J, primary, Mochizuki, T, primary, Chiba, S, primary, Akino, T, primary, Murakumo, M, primary, Miyajima, N, primary, Tsuchiya, K, primary, Murai, S, primary, and Shinohara, N, primary

Published
2020
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22. Therapeutic and analgesic effects of ephedrine alkaloids-free Ephedra Herb extract on complete Freud’s adjuvant-induced arthritis model mouse

Author

Nakamori, S, additional, Miyajima, N, additional, Hyuga, S, additional, Minami, Y, additional, Kazama, H, additional, Hiyama, M, additional, Endo, M, additional, Yang, J, additional, Oshima, N, additional, Uchiyama, N, additional, Amakura, Y, additional, Hakamatsuka, T, additional, Goda, Y, additional, Odaguchi, H, additional, Hanawa, T, additional, and Kobayashi, Y, additional

Published
2019
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24. Correction to: On the P–T–fO2 stability of Fe4O5, Fe5O6, and Fe4O5-rich solid solutions (Contrib Mineral Petrol, (2016), 171, (51), 10.1007/s00410-016-1258-4)

Author

Myhill R., Ojwang D. O., Ziberna L., Frost D. J., Ballaran T. B., Miyajima N., Myhill, R., Ojwang, D. O., Ziberna, L., Frost, D. J., Ballaran, T. B., and Miyajima, N.

Subjects
Fe5O6, Fe4O5, Thermodynamics, Mantle, Deep Earth, Oxygen fugacity
Abstract

There were regrettably a few typos that appeared in the published version of Myhill et al. (2016).

Published
2018

27. High Poisson's ratio of Earth's inner core explained by carbon alloying

Author

Prescher, C., Dubrovinsky, L., Bykova, E., Kupenko, I., Glazyrin, K., Kantor, A., McCammon, C., Mookherjee, M., Nakajima, Y., Miyajima, N., Sinmyo, Ryosuke, Cerantola, V., Dubrovinskaia, N., Prakapenka, V., Rueffer, R., Chumakov, A., Hanfland, M., Prescher, C, Dubrovinsky, L, Bykova, E, Kupenko, I, Glazyrin, K, Kantor, A, Mccammon, C, Mookherjee, M, Nakajima, Y, Miyajima, N, Sinmyo, R, Cerantola, V, Dubrovinskaia, N, Prakapenka, V, Ruffer, R, Chumakov, A, and Hanfland, M

Subjects
XRD, chemistry.chemical_element, Mineralogy, Carbide, symbols.namesake, Natural rubber, extreme condition, Phase (matter), Astrophysics::Solar and Stellar Astrophysics, Composite material, inner core, iron carbide, Mössbauer spectroscopy, Inner core, NIS, Physics::Classical Physics, Poisson's ratio, Core (optical fiber), chemistry, visual_art, visual_art.visual_art_medium, symbols, General Earth and Planetary Sciences, Structure of the Earth, Carbon, Geology
Abstract

Geochemical, cosmochemical, geophysical, and mineral physics data suggest that iron (or iron-nickel alloy) is the main component of the Earth's core. The inconsistency between the density of pure iron at pressure and temperature conditions of the Earth's core and seismological observations can be explained by the presence of light elements. However, the low shear wave velocity and high Poisson's ratio of the Earth's core remain enigmatic. Here we experimentally investigate the effect of carbon on the elastic properties of iron at high pressures and temperatures and report a high-pressure orthorhombic phase of iron carbide, Fe7C3. We determined the crystal structure of the material at ambient conditions and investigated its stability and behaviour at pressures up to 205 GPa and temperatures above 3,700 K using single-crystal and powder X-ray diffraction, Mössbauer spectroscopy, and nuclear inelastic scattering. Estimated shear wave and compressional wave velocities show that Fe7C3 exhibits a lower shear wave velocity than pure iron and a Poisson's ratio similar to that of the Earth's inner core. We suggest that carbon alloying significantly modifies the properties of iron at extreme conditions to approach the elastic behaviour of rubber. Thus, the presence of carbon may explain the anomalous elastic properties of the Earth's core.

Published
2015

28. 93rd annual convention podium and poster abstracts

Author

Davis, C. M., Strong, S. A., Hellinger, M. D., Williamson, P. R., Larach, S. W., Ferrara, A., Blake, T. B., Medich, D. S., Ziv, Y., Oakley, J. R., Reissman, P., Piccirillo, M., Ulrich, A., Nogueras, J. J., Wexner, S. D., Rubin, M. S., Bodenstein, L. E., Kent, K. C., Williamson, M. E. R., Lewis, W. G., Sagar, P. M., Holdsworth, P. J., Johnston, D., Fazio, V. W., Goldblum, J. R., Sirimarco, M. T., Lavery, I. C., Petras, R. E., Treem, W. R., Cohen, J., Davis, P. M., Hyams, J. S., Eu, K. W., Bartolo, D. C. C., Green, J. D., Riether, R. D., Rosen, L., Stasik, J. J., Sheets, J. A., Reed, J., Khubchandani, I. T., Armitage, N. C., Chapman, M., Hardcastle, J. D., Viamonte, M., Plasencia, G., Wiltz, O., Jacobs, M., Finan, P. J., Passaro, M., Church, J. M., McGannon, E., Wilson, M., Hull-Boiner, S., Kollmorgen, C. F., Meagher, A. P., Wolff, B. G., Pemberton, J. H., Martenson, J. A., Ilstrup, D. M., Moran, M. R., Ramos, A., Rothenberger, D. A., Goldberg, S. M., Johnson, D., Madoff, R. D., Wong, W. D., Finne, III, C. O., Konishi, F., Furuta, K., Kanazawa, K., Lockhart, D., Schmitt, S., Caushaj, P. P., Garcia-Aguilar, J., Belmonte, C., Schiesel, E. C., Mazier, W. P., Senagore, A. J., Piccirillo, M. F., Teoh, T. -A., Yoon, K. -S., Paul, R. A. Patino, Lucas, J., Nelson, R., Norton, N., Cautley, E., Schouten, W. R., Briel, J. W., Auwerda, J. J. A., de Graaf, E. J. R., Lowry, A. C., Sentovich, S. M., Blatchford, G. J., Rivela, L. J., Thorson, A. G., Christensen, M. A., Jorge, J. M. N., Yang, Y. K., Shafik, A., Allendorf, J. D. F., Kayton, M. L., Libutti, S. K., Trokel, M. J., Whelan, R. L., Treat, M. R., Nowygrod, R., Bessler, M., Frank, R. E., Saclarides, T. J., Leurgans, S., Speziale, N. J., Drab, E., Rubin, D., Hull, T. L., Schroeder, T. K., Scholefield, J. H., Ogunbiyi, O. A., Smith, J. H. F., Rogers, K., Sharp, F., Longo, W. E., Vernava, III, A. M., Wade, T. P., Coplin, M. A., Virgo, K. S., Johnson, F. E., Brady, M., Kavolius, J., Quan, S. H. Q., Goldstein, E. T., Feldman, S., Shub, H. A., Bennett, D. R., Kumar, R., McMillen, M. A., Thornton, S., Khoury, D. A., Opelka, F. G., Teoh, T -A., Cohen, S. M., Weiss, E. G., Ortiz, H., De Miguel, M., Armendáriz, P., Rodriguez, J., Chocarro, C., Farouk, R., Dorrance, H. R., Duthie, G. S., Rainey, J. B., Morgado, Jr., P. J., Corman, M. L., Kawamura, Y. J., Sawada, T., Muto, T., Nagai, H., Hill, J., MacLennan, I., Binderow, S. R., Daniel, N., Ehrenpreis, E. D., Jensen, J. E., Bonner, G. F., Ruderman, W. B., Milsom, J. W., Gibbs, D. H., Beck, D. E., Hicks, T. C., Timmcke, A. E., Gathright, Jr, J. B., Cheong, D., Lucas, F. V., McGinity, M., Taylor, B. A., Godwin, P., Holdsworth, P., Lewis, W., Quirke, P., Williamson, M., Kokoszka, J., Pavel, D., Abcarian, H., Stephenson, B. M., Morgan, A. R., Salaman, J. R., Wheeler, M. H., Tran, T. C. K., Willemsen, W., Kuijpers, H. C., Lehman, J. F., Wiseman, J. S., MacFie, J., Sedman, P., May, J., Mancey-Jones, B., Johnstone, D., Nwariaku, F. E., Rochon, R. B., Huber, P. J., Carrico, C. J., Ortega, A., Beart, R., Winchester, D., Steele, G., Green, R., Caushaj, P. F., Devereaux, D., Griffey, S., Reiver, D., Kmiot, W. A., Baker, R., Luchtefeld, M. A., Anthone, G., Schlinkert, R., Roig, J. V., Villoslada, C., Solana, A., Alos, R., Hinojosa, J., Lledo, S., Johnson, D. R. E., Buie, W. D., Jensen, L. L., Heine, J., Hoffmann, B., Timmcke, A., Hicks, T., Opelka, F., Beck, D., Sousa, Jr., A., AraÚjo, S. A., Damico, F. M., Cordeiro, A. C., Pinotti, H. W., Gama, A. H., Fengler, S., Pearl, R., Orsay, C., Seow-Choen, F., Ho, J. M. S., Wiltz, O. H., Torregrosa, M., Brasch, R. C., Bufo, A. J., Krienberg, P., Johnson, G. P., Gowen, G. F., Mullen, P. D., Behrens, D., Hughes, T. G., Wynn, M., Pollack, J. S., Rajagopal, A. S., Huynh, T., Schanbacher, C., Hickson, W. G. E., Yang, Y. -K., Heymen, S., Choi, S. -K., Teoh, T. -A., Wexner, S. D., Vaccaro, C. A., Teoh, T. A., Nogueras, J. J., Choi, S. K., Cheong, D. M. O., Salanga, V. D., MacDonald, A., Baxter, J. N., Finlay, I. G., Mellgren, A., Bremmer, S., Dolk, A., Gillgren, P., Johansson, C., Ahlbäck, S. O., Udén, R., Holmström, B., Ferrara, A., O'Donovan, S., Larach, S. W., Williamson, P. R., Neto, J. A. Reis, Ciquini, S., Quilici, F. A., Reis, Jr., J. A., Torrabadella, L., Salgado, G., Whelan, R. L., Horvath, K. D., Golub, R., Ahsan, H., Cirocco, W., Ziv, Y., Fazio, V. W., Oakley, J. R., Church, J. M., Milsom, J. W., Lavery, L. C., Cohen, S. M., Kmiot, W. A., Reiver, D., Reissman, P., Weiss, E. G., Alós, R., García-Granero, E., Roig, J. V., Uribe, N., Sala, C., Lledo, S., Ozuner, G., Strong, S. A., Bufo, A. J., Daniels, G., Lieberman, R. C., Feldman, S., Lucas, F. V., Longo, W. E., Polites, G., Deshpande, Y., Vernava, A. M., Niehoff, M., Chandel, B., Berglund, D. D., Madoff, R. D., Gemlo, B. T., Spencer, M. P., Goldberg, S. M., Lowry, A. C., Marcello, P. W., Roberts, P. L., Schoetz, D. J., Murray, J. J., Coller, J. A., Veidenheimer, M. C., Koltun, W. A., Bloomer, M. M., Colony, P., Ruggeiro, F., Fleshner, P. R., Michelassi, F., Lewis, W., Williamson, M., Holdsworth, P., Finan, P., Ash, D., Johnston, D., Moran, M. R., Ramos, A., Rothenberger, D. A., Antonenko, D. R., Khanduja, K. S., Fitzgerald, S. D., Meagher, A. P., Moniz-Pereira, P., Wolff, B. G., Outwater, E. K., Marks, G. J., Mohiuddin, M., Sagar, P. M., Hartley, M. N., Mancey-Jones, B., Sedman, P., May, J., MacFie, J., Holbrook, R. F., Rodriguez-Bigas, M. A., Ramakrishnan, K., Palmer, M. L., Petrelli, N. J., Takahashi, T., Nivatvongs, S., Batts, K. P., Lucas, S. W., Klein, S. N., Keidan, R. D., Bannon, J. P., Zhou, J., Armitage, N. C., Hunt, L. M., Robinson, M. H., Hugkulstone, C. E., Clarke, B., Vernon, S. A., Gregson, R. H., Hardcastle, J. D., Ryan, M., Dutta, S., Levine, A., Ortega, A., Anthone, G., Beart, R., Dominguez, J. M., Saclarides, T. J., Bolan, P., Bines, S. D., Adachi, M., Watanabe, T., Sawada, T., Okinaga, K., Muto, T., Hase, K., Shatney, C., Mochizuki, H., Johnson, D., Ure, T., Dehghan, K., Andrus, C. A., Daniel, G. L., D'Emilia, J. C., Rodriguez-Bigas, M., Suh, O. K., Brewer, D. A., Fung, C., Chapuis, P., Bokey, E. L., Garcia, J. C., Banerjee, S., Remzi, F. H., Lavery, I. C., Jorge, J. M. N., Ger, G. C., Gonzalez, L., Gee, A. S., Roe, A. M., Durdey, P., Kaye, M. D., Kyzer, S., Gordon, P. H., Hasegawa, M., Bun, P. Tae, Ikeuchi, D., Onodera, H., Imamura, M., Maetani, S., Blake, T., Hellinger, M., Grewal, H., Klimstra, D. S., Cohen, A. M., Guillem, J. G., Rooney, P. S., Gifford, K. -A., Clarke, P. A., Kuhn, J. A., Bryce, K., Frank, N., Dignan, R. D., Lichliter, W. E., Franko, E., Jacobson, R. M., Preskitt, J. T., Lieberman, Z., Tulanon, P., Steinbach, H., McCarty, T., Simons, T., Plasencia, G., Viamonte, M., Wiltz, O., Jacobs, M., Chen, W. S., Leu, S. Y., Hsu, H., Bessler, M., Halverson, A., Kayton, M. L., Treat, M. R., Nowygrod, R., Congilosi, S., Madoff, R., Wong, W. D., Rothenberger, D., Buie, W. D., Paterson, R., Cartmill, J. A., Trokel, M. J., Gingold, B. S., Cooper, M., Gorfine, S. R., Bauer, J. J., Gelernt, I. M., Kreel, I., Harris, M. T., Vallejo, J. F., Kestenberg, A., Miyajima, N., Kano, N., Ishikawa, Y., Sakai, S., Yamakawa, T., Otchy, D. P., Van Heerden, J. A., Ilstrup, D. M., Weaver, A. L., Winter, L. D., Mav, J., Lee, P. Y., Vetto, J. T., Sullivan, E. S., Rabkin, J., Mayoral, J. L., Matas, A. J., Bove, P., Visser, T., Barkel, D., Villalba, M., Bendick, P., Glover, J., Golub, R. W., Cirocco, W. C., Daniel, N., Altringer, W., Domingues, J. M., Brubaker, L. T., Smith, C. S., Kumar, S., and Gilbert, P.

Published
1994
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30. Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma

Author

1000010399842, Abe, T., Minami, K., Harabayashi, T., Sazawa, A., Chiba, H., Kikuchi, H., Miyata, H., Matsumoto, R., Osawa, T., Maruyama, S., IshizakiIshizaki, J., Mochizuki, T., Chiba, S., Akino, T., Murakumo, M., Miyajima, N., Tsuchiya, K., Murai, S., 1000090250422, Shinohara, N., 1000010399842, Abe, T., Minami, K., Harabayashi, T., Sazawa, A., Chiba, H., Kikuchi, H., Miyata, H., Matsumoto, R., Osawa, T., Maruyama, S., IshizakiIshizaki, J., Mochizuki, T., Chiba, S., Akino, T., Murakumo, M., Miyajima, N., Tsuchiya, K., Murai, S., 1000090250422, and Shinohara, N.

Abstract

Objective: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). Methods: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. Results: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. Conclusions: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Published
2019

31. Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma

Author

Abe, T., Minami, K., Harabayashi, T., Sazawa, A., Chiba, H., Kikuchi, H., Miyata, H., Matsumoto, R., Osawa, T., Maruyama, S., IshizakiIshizaki, J., Mochizuki, T., Chiba, S., Akino, T., Murakumo, M., Miyajima, N., Tsuchiya, K., Murai, S., Shinohara, N., Abe, T., Minami, K., Harabayashi, T., Sazawa, A., Chiba, H., Kikuchi, H., Miyata, H., Matsumoto, R., Osawa, T., Maruyama, S., IshizakiIshizaki, J., Mochizuki, T., Chiba, S., Akino, T., Murakumo, M., Miyajima, N., Tsuchiya, K., Murai, S., and Shinohara, N.

Abstract

Objective: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). Methods: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. Results: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. Conclusions: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Published
2019

32. Abstracts

Author

Rosen, L., Reed, J., Ufberg, D., Thorburn, H., Carter, K., Goldberg, J., Finlay, I. G., Church, J. M., Hill, G. L., Carter, F. M., Cohen, Z., McLeod, R. S., Bauer, J. J., Sher, M. E., Gelernt, I. M., Crim, R. W., Fazio, V. W., Lavery, I. C., Williams, J. G., Nemer, F. D., Rothenberger, D. A., Goldberg, S. M., Hyman, N. H., Tuckson, W. B., Deutsch, A. A., Gregoire, R., Cullen, J., Johnson, G. P., Wolff, B. G., Koltun, W., Schoetz, Jr., D. J., Roberts, P. L., Murray, J. J., Coller, J. A., Veidenheimer, M. C., Keighley, M. R. B., Hosie, K., Sakaguchi, M., Tudor, R., Kmiot, W., Ambroze, Jr., W. L., Dozois, R. R., Pemberton, J. H., Kelly, K. A., Wiltz, O., Hashmi, H., Fucini, C., Thayer, M. L., Madoff, R. D., Jacobs, D. M., Bubrick, M. P., Galandiuk, S., Tsao, J., Ilstrup, D. M., Duthie, G. S., Bartolo, D. C. C., Miller, R., Pinho, M., Kunin, J. D., Fleshman, J. W., Kodner, I. J., Fry, R. D., Wexner, S. D., Jagelman, D. G., Corredor, C., Salanga, V., Scholefield, J. H., Whatrup, C., Talbot, I. C., Northover, J. M. A., Sonnex, C., Safavi, A., Gottesman, L., Dailey, T., Moenning, S., Nightengale, S., Simonton, T., Huber, P., Odom, C., Kaplan, E., Strong, S. A., Milsom, J. W., Taylor, C. W., Cho, C. C., Stewart, W. R. C., Hartmann, R. F., Khanduja, K. S., Aguilar, P. S., Rahman, S. M., Arnold, M. W., Caushaj, P., Viratyosin, S., French, T., Madoff, R., Karamjit, S., Meesig, D. M., Macleod, C. A. H., Balcos, E. G., Buls, J. G., Nelson, H., Donohue, J. H., McKean, D. J., Leu, S. Y., Wang, S. R., Hsu, H., Ramanujam, P. S., Alberts, D. S., Clark, L., Ritenbaugh, C., Rowley, S., Kane, N., Jones, C., Davies, A., Baker, P., Neoptolemos, J. P., Devereux, D. F., Robertson, F. M., Spain, D. A., Cance, W. G., Cohen, A. M., Sigurdson, E. R., Enker, W. E., Konishi, F., Yasuda, Y., Ochiai, S., Kanazawa, K., Davis, M., Medina, V., Miller, D., Fielding, L. P., Prats, I., Berman, M., West, B., Savoca, P. E., Ballantyne, G. H., Flannery, J. T., Modlin, I. M., Tsukada, K., Jagelman, D. A., McGannon, E. M., Schroeder, T., Sakamoto, G. D., MacKeigan, J. M., Opelka, F., Timmcke, A., Gathright, J. B., Hicks, T., Ray, J., McKee, C. C., Ragland, J. J., Myers, J. O., Christie, J. P., Marrazzo, III, J., Flemming, F. X., Longo, W. E., Pollard, C. W., Nivatvongs, S., Rojanasakul, A., Jetmore, A. B., Baker, J., Wiltz, O. H., McKee, R. F., Lauder, J., Poon, F., Aitchison, M., Fleshman, James W., Dreznik, Zeev, Kodner, Ira J., Fry, Robert D., Kerner, B. A., Labow, S., Hoexter, B., Moseson, M., Cheape, J. D., Bowinkelman, K., Dziki, A. J., Malthaner, R. A., Harmon, J. W., Saini, N., Duncan, M. D., Fernicola, M. T., Fischer, B. A., Hakki, F. Z., Trad, K. S., Ugarte, R., Senagore, A. J., Mazier, W. P., Kilbride, M., Herrera, L., Goumas, W., Petrelli, N., Bailey, H. R., Huval, W. V., Max, E., Smith, K. W., Marks, G., Mohiuddin, M., Basile, M., Eitan, A., Wolff, B., Dozois, R., Devine, R., Beart, R., Kelly, A., Unti, J. A., Orsay, C. P., Pearl, R. K., Nelson, R. L., Duarte, B., Prasad, M. L., Abcarian, H., Senagore, A., Milson, J. W., Strong, S., Walshaw, R. K., Chaudry, I. H., Hojo, K., Sugihara, K., Katunuma, K., Vernava, A., Beart, R. W., Stewart, J., Diament, R. H., Salter, M., Brennan, T. G., Sheikh, F., Khubchandani, I. T., Miyajima, N., Uematsu, Y., Kodaira, S., Teramoto, T., Orrom, W. J., Duthie, G., Corne, H., Blatchford, G. J., Perry, R. E., Christensen, M. A., Thorson, A. G., Dreznik, Zeev, Wong, W. D., Jensen, L. L., Lee, K. H., Yoon, Choong, Joo, H. Z., Levien, D. H., Gibbons, S., Begos, D., Byrne, D. W., Gordon, P. H., Bégin, L. R., Mitmaker, B., Saclarides, T., Bhattacharyya, A., Britton, C., Stone, J. M., Lowry, A. C., Moran, M., Launer, D. P., McReynolds, D. G., Eastman, A. B., Peck, J. J., Rozycki, G. S., Ramanujam, Paravasthu S., Bellapravalu, Sharad, Venkatesh, Kurakurachi S., Griffin, Kathleen M., Vernava, A. M., Beckman, R., Andrus, C., Johnson, F., Herrmann, V., Kaminski, D. L., Wetter, L. A., Dinneen, M., Levitt, M., Motson, R. W., Rohrer, D. A., Bapna, M. S., Rotstein, L. E., Radhakrishnan, Jayant, Shrader, Charisse, Ravo, B., Frattaroli, F. M., Reggio, D., Litchy, W. J., Hanson, R. B., Morgado, Pedro J., Alfaro, Rodrigo, Alfonzo, Rafael, Vachon, D. A., Oliver, G. C., Eisenstat, T. E., Salvati, E. P., Rubin, R. J., Clay, R. P., Kumar, Sanath, Guillem, J. G., Levy, M. F., Hsieh, L. L., Johnson, M. D., Forde, K. A., Weinstein, I. B., Bilchik, A. J., Fleming, F. X., Pernikoff, B. J., Goldenring, J. R., Fozard, J. B., Lowndes, R. H., Young, H. L., Sackier, J., Leite, J. F. M. S., Fausto-Pontes, Martins, M. I., Kmiot, W. A., Youngs, D. J., Harding, L. K., Hesselwood, S. R., Smith, N., Hartley, M. G., Hudson, M. J., Hill, M. J., Gent, A. E., Grace, R. H., Swarbrick, E. T., Hellier, M. D., Procaccino, J. A., Oakley, J. R., Flanagan, Jr., R. A., Lapos, L., Riether, R. D., Stasik, J. J., Trostle, D. R., Sheets, J. A., Ferrara, A., Armstrong, D. N., Bjorck, S., McMillen, M. A., Nicholson, J. D., Halleran, D. R., Trivisonno, D. P., Ziegler, J. A., Lott, J., Saleeby, R., Sullivan, T., and Nelson, R.

Published
1990
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34. Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma

Author

Abe, T, primary, Minami, K, primary, Harabayashi, T, primary, Sazawa, A, primary, Chiba, H, primary, Kikuchi, H, primary, Miyata, H, primary, Matsumoto, R, primary, Osawa, T, primary, Maruyama, S, primary, IshizakiIshizaki, J, primary, Mochizuki, T, primary, Chiba, S, primary, Akino, T, primary, Murakumo, M, primary, Miyajima, N, primary, Tsuchiya, K, primary, Murai, S, primary, and Shinohara, N, primary

Published
2019
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38. On the P-T-fO2 stability of Fe4O5, Fe5O6 and Fe4O5-rich solid solutions

Author

Myhill R, Ojwang DO, Ziberna L, Frost D, Boffa Ballaran T, Miyajima N, Myhill, R, Ojwang, Do, Ziberna, L, Frost, D, Boffa Ballaran, T, and Miyajima, N

Subjects
Thermodynamic, Fe5O6, Fe4O5, Thermodynamics, Oxygen fugacity, Mantle, Deep Earth
Abstract

The high-pressure phases Fe4O5 and Fe506 have recently been added to the list of known iron oxides. As mixed -valence phases, it has been suggested that they could form in the Earth's mantle once the dominant minerals become saturated in ferric iron. The possibility that Fe4O5 could exist in the mantle is also supported by the fact that it forms extensive solid solutions with both Mg2+ and Cr3+. In this study, we present the results of high-pressure and high-temperature multi -anvil experiments performed between 5 and 24 GPa at 1000-1400 degrees C aimed at constraining the stability field of the Fe4O5 phase. We combine these results with published phase equilibria, equation of state and Fe Mg partitioning data to estimate the thermodynamic properties of Fe4O5, Fe5O6 and the (Mg,Fe)(2)Fe2O5 solid solution. Using our thermodynamic model, the oxygen fugacity at which the high-pressure iron oxides become stable is calculated and the redox stability of (Mg,Fe)(2)Fe2O5 in an assemblage of olivine and pyroxene is calculated as a function of the bulk Fe/(Fe + Mg) ratio. Fe4O5 and (Mg,Fe)(2)Fe2O5 are stable at oxygen fugacities higher than the diamond stability field and are, therefore, unlikely to be found as inclusions in diamonds. The stability field of Fe5O6, on the other hand, extends to oxygen fugacities compatible with diamond formation. Using the Mg Fe solid solution model, we show that Fe4O5-structured phases would be restricted to aluminium -poor environments in the mantle such as dunites or silica iron oxide rich sediments transported into the mantle via subduction.

Published
2016

39. Iron release in aqueous environment by fresh volcanic ash from Mount Etna (Italy) and Popocatépetl (Mexico) volcanoes

Author

Capitani, G, Miyajima, N, Sulpizio, R, D'Addabbo, M, Galimberti, L, Guidi, M, Andreozzi, G, Capitani, GC, Andreozzi, GB, Capitani, G, Miyajima, N, Sulpizio, R, D'Addabbo, M, Galimberti, L, Guidi, M, Andreozzi, G, Capitani, GC, and Andreozzi, GB

Abstract

In this study, we performed leaching experiments for timescales of hours-to-months in deionized water on fresh volcanic ash from Mt. Etna (Italy) and Popocatépetl (Mexico) volcanos to monitor Fe release as a function of ash mineral chemistry and size, with the aim of clarifying Fe release mechanisms and eventually evaluating the impact of volcanic ash on marine and lacustrine environments. To define sample mineralogy and Fe speciation, inclusive characterization was obtained by means of XRF, SEM, XRPD, EELS and Mössbauer spectroscopies. For Etna and Popocatépetl samples, glass proportions were quantified at 73 and 40%, Fe2O3 total contents at 11.6–13.2 and 5.8 wt%, and Fe3+/FeTot ratios at 0.33 and 0.23, respectively. Leaching experiments showed that significant amounts of iron, ~ 30 to 150 and ~ 750 nmol g−1 l−1 for pristine Etna and Popocatépetl samples, respectively, are released within the first 30 min as a function of decreasing particle size (from 1 to 0.125 mm). The Popocatépetl sample showed a very sustained Fe release (up to 10 times Etna samples) all along the first week, with lowest values never below 400 nmol g−1 l−1 and a maximum of 1672 nmol g−1 l−1 recorded after 5 days. This sample, being composed of very small particles (average particle size 0.125 mm) with large surface area, likely accumulated large quantities of Fe-bearing sublimates that quickly dissolved during leaching tests, determining high Fe release and local pH decrease (that contributed to release more Fe from the glass) at short timescale (hours-to-days). The fractional Fe solubility (FeS) was 0.004–0.011 and 0.23% for Etna and Popocatépetl samples, respectively, but no correlation was found between Fe released in solution and either ash Fe content, glass/mineral ratio or mineral assemblage. Results obtained suggest that volcanic ash chemistry, mineralogy and particle size assume a relevant role on Fe release mostly in the medium-to-long timescale, while Fe release in the short ti

Published
2018

40. High Poisson's ratio of Earth's inner core explained by carbon alloying

Author

Prescher, C, Dubrovinsky, L, Bykova, E, Kupenko, I, Glazyrin, K, Kantor, A, Mccammon, C, Mookherjee, M, Nakajima, Y, Miyajima, N, Sinmyo, R, Cerantola, V, Dubrovinskaia, N, Prakapenka, V, Ruffer, R, Chumakov, A, Hanfland, M, Prescher C, Dubrovinsky L, Bykova E, Kupenko I, Glazyrin K, Kantor A, McCammon C, Mookherjee M, Nakajima Y, Miyajima N, Sinmyo R, Cerantola V, Dubrovinskaia N, Prakapenka V, Ruffer R, Chumakov A, Hanfland M, Prescher, C, Dubrovinsky, L, Bykova, E, Kupenko, I, Glazyrin, K, Kantor, A, Mccammon, C, Mookherjee, M, Nakajima, Y, Miyajima, N, Sinmyo, R, Cerantola, V, Dubrovinskaia, N, Prakapenka, V, Ruffer, R, Chumakov, A, Hanfland, M, Prescher C, Dubrovinsky L, Bykova E, Kupenko I, Glazyrin K, Kantor A, McCammon C, Mookherjee M, Nakajima Y, Miyajima N, Sinmyo R, Cerantola V, Dubrovinskaia N, Prakapenka V, Ruffer R, Chumakov A, and Hanfland M

Abstract

Geochemical, cosmochemical, geophysical, and mineral physics data suggest that iron (or iron-nickel alloy) is the main component of the Earth's core. The inconsistency between the density of pure iron at pressure and temperature conditions of the Earth's core and seismological observations can be explained by the presence of light elements. However, the low shear wave velocity and high Poisson's ratio of the Earth's core remain enigmatic. Here we experimentally investigate the effect of carbon on the elastic properties of iron at high pressures and temperatures and report a high-pressure orthorhombic phase of iron carbide, Fe7C3. We determined the crystal structure of the material at ambient conditions and investigated its stability and behaviour at pressures up to 205 GPa and temperatures above 3,700 K using single-crystal and powder X-ray diffraction, Mössbauer spectroscopy, and nuclear inelastic scattering. Estimated shear wave and compressional wave velocities show that Fe7C3 exhibits a lower shear wave velocity than pure iron and a Poisson's ratio similar to that of the Earth's inner core. We suggest that carbon alloying significantly modifies the properties of iron at extreme conditions to approach the elastic behaviour of rubber. Thus, the presence of carbon may explain the anomalous elastic properties of the Earth's core.

Published
2015

45. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Author

Petrylak, D.P. de Wit, R. Chi, K.N. Drakaki, A. Sternberg, C.N. Nishiyama, H. Castellano, D. Hussain, S. Fléchon, A. Bamias, A. Yu, E.Y. van der Heijden, M.S. Matsubara, N. Alekseev, B. Necchi, A. Géczi, L. Ou, Y.-C. Coskun, H.S. Su, W.-P. Hegemann, M. Percent, I.J. Lee, J.-L. Tucci, M. Semenov, A. Laestadius, F. Peer, A. Tortora, G. Safina, S. del Muro, X.G. Rodriguez-Vida, A. Cicin, I. Harputluoglu, H. Widau, R.C. Liepa, A.M. Walgren, R.A. Hamid, O. Zimmermann, A.H. Bell-McGuinn, K.M. Powles, T. Wong, S.-L.S. Tan, T.H. Hovey, E.J. Clay, T.D. Ng, S.S.W. Rutten, A. Machiels, J.-P. Dumez, H. Cheng, S.Y.-S. Ferrario, C. Sengeloev, L. Jensen, N.V. Thibault, C. Laguerre, B. Joly, F. Flechon, A. Culine, S. Becht, C. Niegisch, G. Stöckle, M. Grimm, M.-O. Gakis, G. Schultze-Seemann, W. Kalofonos, H. Mavroudis, D. Papandreou, C. Karavasilis, V. Révész, J. Geczi, L. Rosenbaum, E. Leibowitz-Amit, R. Kejzman, D. Sarid, D. Scagliotti, G.V. Bracarda, S. Massari, F. Osawa, T. Miyajima, N. Shinohara, N. Fukuta, F. Ohyama, C. Obara, W. Yamashita, S. Tomita, Y. Kawai, K. Fukasawa, S. Oyama, M. Yonese, J. Nagata, M. Uemura, M. Nishimura, K. Kawakita, M. Tsunemori, H. Hashine, K. Inokuchi, J. Yokomizo, A. Nagamori, S. Lee, H.J. Park, S.H. Rha, S.Y. Kim, Y.J. Lee, Y.-G. Cortés, L.V. Flores, C.L.U. Blaisse, R.J.B. Erdkamp, F.L.G. Aarts, M.J.B. Wojcik-Tomaszewska, J. Tomczak, P. Sikora-Kupis, B. Schenker, M. Herzal, A.A. Udrea, A.A. Karlov, P. Fomkin, R. Pulido, E.G. Mignorance, J.I.D. Gauna, D.C. Rodríguez-Vida, A. Su, Y.-L. Lin, C.-L. Lin, C.-C. Yeh, S.-P. Çiçin, I. Erman, M. Urun, Y. Golovko, Y. Bondarenko, I. Sinielnikov, I. Crabb, S. Syndikus, I. Huddart, R. Sundar, S. Chowdhury, S. Sarwar, N. Flaig, T. Pan, C.X. Schwarz, J. Cultrera, J. Hainsworth, J. Herms, B. Lawler, W. Lowe, T. Tagawa, S. Aragon-Ching, J. Vaishampayan, U.

Abstract

Background Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab—a human IgG1 VEGFR-2 antagonist—or placebo in this patient population. Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m2 plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96–4·47] vs 2·76 months [2·60–2·96]; hazard ratio [HR] 0·757, 95% CI 0·607–0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8–30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4–18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1–2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. Interpretation To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. Funding Eli Lilly and Company. © 2017 Elsevier Ltd

Published
2017

47. High pressure and high temperature phase transformations in LiNbO[sub 3].

Author

Mukaide, T., Yagi, T., Miyajima, N., Kondo, T., Sata, N., and Kikegawa, T.

Subjects
PHASE transitions, HIGH pressure (Technology), HIGH temperatures, FERROELECTRIC crystals
Abstract

A behavior of LiNbO[sub 3] under high pressure and temperature has been studied up to 90 GPa by means of high pressure in situ x-ray observations. Recovered samples were analyzed by transmission electron microscope (TEM). When the LiNbO[sub 3] was compressed at room temperature, a transformation occurred at about 25 GPa. The powder x-ray diffraction pattern of this "room-temperature and high-pressure" (RT-HP) phase was successfully explained by the NaIO[sub 3]-type structure. No further transformation was observed at room temperature up to 90 GPa and reverse transition to starting phase occurred at about 10 GPa, thus this phase was unquenchable on release of pressure. When this RT-HP phase was heated at above 30 GPa, a phase appeared which can be recovered to ambient condition. X-ray diffraction and TEM analysis of this "high-temperature and high-pressure" (HT-HP) phase clarified that this phase has hexagonal symmetry with a most likely space group of P6[sub 3]. The quenched sample reverts to the starting phase on heating above 650 K. This HT-HP phase is opaque, suggesting the change of electronic property. The density of these RT-HP and HT-HP phases are, respectively, 21% and 23% higher compared to the starting LiNbO[sub 3] phase at ambient condition. [ABSTRACT FROM AUTHOR]

Published
2003
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50. Navier–Stokes equations on the [formula omitted]-plane: Determining modes and nodes.

Author

Miyajima, N. and Wirosoetisno, D.

Subjects
*NAVIER-Stokes equations, *CORIOLIS force, *GRASHOF number, *CONVECTIVE flow, *FLUID dynamics
Abstract

Abstract We revisit the 2d Navier–Stokes equations on the periodic β -plane, with the Coriolis parameter varying as β y , and obtain bounds on the number of determining modes and nodes of the flow. The number of modes and nodes scale as c G 0 1 ∕ 2 + c ′ (M ∕ β) 1 ∕ 2 and c G 0 2 ∕ 3 + c ′ (M ∕ β) 1 ∕ 2 , respectively, where the Grashof number G 0 = | f v | L 2 ∕ (μ 2 κ 0 2) and M involves higher derivatives of the forcing f v. For large β (strong rotation), this results in fewer degrees of freedom than the classical (non-rotating) bound that scales as c G 0. [ABSTRACT FROM AUTHOR]

Published
2019
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