364 results on '"de Castro D"'
Search Results
2. The s process in AGB stars as constrained by a large sample of Barium stars
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Cseh, B., Lugaro, M., D'Orazi, V., de Castro, D. B., Pereira, C. B., Karakas, A. I., Molnár, L., Plachy, E., Szabó, R., Pignatari, M., and Cristallo, S.
- Subjects
Astrophysics - Solar and Stellar Astrophysics - Abstract
Context. Barium (Ba) stars are dwarf and giant stars enriched in elements heavier than iron produced by the slow neutron-capture process (s process). They belong to binary systems where the primary star evolved through the asymptotic giant branch (AGB) phase,during which it produced the s-process elements and transferred them onto the secondary, now observed as a Ba star. Aims. We compare the largest homogeneous set of Ba giant star observations of the s-process elements Y, Zr, La, Ce, and Nd with AGB nucleosynthesis models to reach a better understanding of the s process in AGB stars. Methods. By considering the light-s (ls: Y and Zr) heavy-s (hs: La, Ce, and Nd) and elements individually, we computed for the first time quantitative error bars for the different hs-element/ls-element abundance ratios, and for each of the sample stars. We compared these ratios to low-mass AGB nucleosynthesis models. We excluded La from our analysis because the strong La lines in some of the sample stars cause an overestimation and unreliable abundance determination, as compared to the other observed hs-type elements. Results. All the computed hs-type to ls-type element ratios show a clear trend of increasing with decreasing metallicity with a small spread (less than a factor of 3). This trend is predicted by low-mass AGB models where 13C is the main neutron source. The comparison with rotating AGB models indicates the need for the presence of an angular momentum transport mechanism that should not transport chemical species, but significantly reduce the rotational speed of the core in the advanced stellar evolutionary stages. This is an independent confirmation of asteroseismology observations of the slow down of core rotation in giant stars, and of rotational velocities of white dwarfs lower than predicted by models without an extra angular momentum transport mechanism., Comment: 15 pages, 7 figures, accepted for publication in Astronomy and Astrophysics
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- 2018
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3. Chemical abundances and kinematics of barium stars
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de Castro, D. B., Pereira, C. B., Roig, F., Jilinski, E., Drake, N. A., Chavero, C., and Silva, J. V. Sales
- Subjects
Astrophysics - Solar and Stellar Astrophysics - Abstract
In this paper we present an homogeneous analysis of photospheric abundances based on high-resolution spectroscopy of a sample of 182 barium stars and candidates. We determined atmospheric parameters, spectroscopic distances, stellar masses, ages, luminosities and scale height, radial velocities, abundances of the Na, Al, $alpha$-elements, iron-peak elements, and s-process elements Y, Zr, La, Ce, and Nd. We employed the local-thermodynamic-equilibrium model atmospheres of Kurucz and the spectral analysis code {\sc moog}. We found that the metallicities, the temperatures and the surface gravities for barium stars can not be represented by a single gaussian distribution. The abundances of $alpha$-elements and iron peak elements are similar to those of field giants with the same metallicity. Sodium presents some degree of enrichment in more evolved stars that could be attributed to the NeNa cycle. As expected, the barium stars show overabundance of the elements created by the s-process. By measuring the mean heavy-element abundance pattern as given by the ratio [s/Fe], we found that the barium stars present several degrees of enrichment. We also obtained the [hs/ls] ratio by measuring the photospheric abundances of the Ba-peak and the Zr-peak elements. Our results indicated that the [s/Fe] and the [hs/ls] ratios are strongly anti-correlated with the metallicity. Our kinematical analysis showed that 90% of the barium stars belong to the thin disk population. Based on their luminosities, none of the barium stars are luminous enough to be an AGB star, nor to become self-enriched in the s-process elements. Finally, we determined that the barium stars also follow an age-metallicity relation., Comment: 30 pages, 26 figures, 18 tables, accepted for publication in MNRAS
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- 2016
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4. The Mesozoic Equatorial Atlantic Magmatic Province (EQUAMP) : A New Large Igneous Province in South America
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Hollanda, M. H. B. M., Archanjo, C. J., Macedo Filho, A. A., Fossen, H., Ernst, R. E., de Castro, D. L., Melo, A. C., Oliveira, A. L., Litvin, Yuri, Series Editor, Jimenez-Franco, Abigail, Series Editor, Srivastava, Rajesh K., editor, Ernst, Richard E., editor, and Peng, Peng, editor
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- 2019
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5. Design and high temperature behavior of novel heat resistant steels strengthened by high density of stable nanoprecipitates
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Vivas, J., De-Castro, D., Altstadt, E., Houska, M., San-Martín, D., and Capdevila, C.
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- 2020
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6. Correlation between fluoride release, surface hardness and diametral tensile strength of restorative glass ionomer cements
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Pardi, M., primary, da Cunha, B., additional, Cunha, H., additional, Marques, Me., additional, Ribeiro, K., additional, Cruz, C., additional, Costa, C., additional, Lepri, C., additional, and de Castro, D., additional
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- 2024
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7. Influence of Er:YAG and ND:YAG laser irradiation and fluoride application on surface roughness and dentin surface wear after erosive challenge - An in vitro study
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Corrêa, N., primary, Dibb, R., additional, Geraldo-Martins, V., additional, Madalena, I., additional, Faraoni, J., additional, Oliveira, MM., additional, de Castro, D., additional, and Lepri, C., additional
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- 2024
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8. Direct observation of creep strengthening nanoprecipitate formation in ausformed ferritic/martensitic steels
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Vivas, J., De-Castro, D., Poplawsky, J.D., San-Martín, D., and Capdevila, C.
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- 2019
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9. CD-62\degree1346: an extreme halo or hypervelocity CH~star?
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Pereira, C. B., Jilinski, E., Drake, N. A., de Castro, D. B., Ortega, V. G., Chavero, C., and Roig, F.
- Subjects
Astrophysics - Solar and Stellar Astrophysics - Abstract
High-velocity halo stars provide important information about the properties of the extreme Galactic halo. The study of unbound and bound Population II stars permits us to better estimate the mass of the halo.} {We carried out a detailed spectroscopic and kinematic study and have significantly refined the distance and the evolutionary state of the star. Its atmospheric parameters, chemical abundances and kinematical properties were determined using high-resolution optical spectroscopy and employing the local-thermodynamic-equilibrium model atmospheres of Kurucz and the spectral analysis code {\sc moog}. We found that CD-62$\degr$1346 is a metal-poor ([Fe/H]=$-$1.7) evolved giant star with $T_{\rm eff}=5300$ K and $\log g=1.7$. The star exhibits high carbon and s-element abundances typical of CH stars. It is also a lead star. Our kinematic analysis of its 3D space motions shows that this star has a highly eccentric ($e=0.91$) retrograde orbit with an apogalactic distance of $\sim 100$ kpc, exceeding by a factor of three the distance to the Magellanic Clouds. The star travels with very high velocity relative to the Galactocentric reference frame ($V_{\rm GRF}=570$ km\,s$^{-1}$). CD-62$\degr$1346 is an evolved giant star and not a subgiant star, as was considered earlier. Whether it is bound or unbound to the Galaxy depends on the assumed mass and on the adopted Galactic potential. We also show that the star HD 5223 is another example of a high-velocity CH star that exceeds the Galactic escape velocity. Possible origins of these two high-velocity stars are briefly discussed. CD-62$\degr$1346 and HD 5223 are the first red giant stars to join the restricted group of hypervelocity stars., Comment: Accepted for publication in Astronomy and Astrophysics
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- 2012
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10. Effect of ausforming temperature on creep strength of G91 investigated by means of Small Punch Creep Tests
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Vivas, J., Capdevila, C., Altstadt, E., Houska, M., Serrano, M., De-Castro, D., and San-Martín, D.
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- 2018
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11. High hardness and retained austenite stability in Si-bearing hypereutectoid steel through new heat treatment design principles
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Sourmail, T., Caballero, F.G., Moudian, F., De Castro, D., and Benito, M.
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- 2018
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12. Investigating the feasibility of tumour molecular profiling in gastrointestinal malignancies in routine clinical practice
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Moorcraft, S.Y., Gonzalez de Castro, D., Cunningham, D., Jones, T., Walker, B.A., Peckitt, C., Yuan, L.C., Frampton, M., Begum, R., Eltahir, Z., Wotherspoon, A., Teixeira Mendes, L.S., Hulkki Wilson, S., Gillbanks, A., Baratelli, C., Fotiadis, N., Patel, A., Braconi, C., Valeri, N., Gerlinger, M., Rao, S., Watkins, D., Chau, I., and Starling, N.
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- 2018
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13. Pearlite Transformation in a Deformed TRIP/TWIP Austenitic Steel
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De Castro, D., Vivas, J., Rementeria, R., Aranda, M. M., Jimenez, J. A., and Capdevila, C.
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- 2019
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14. Protocolo diagnóstico de las lesiones quísticas hepáticas
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de Castro, D. Álvarez, Mateos, R. Martín, de la Iglesia, S. Pérez, and Cardona, J. López
- Abstract
El diagnóstico de lesiones quísticas hepáticas supone un hallazgo incidental cada vez más frecuente en nuestro entorno, debido al aumento de la disponibilidad de las pruebas de imagen. Por ello, conocer las distintas lesiones quísticas y su manejo es crucial en la práctica clínica. Para el diagnóstico diferencial debemos tener en cuenta los antecedentes personales del paciente, la historia clínica y, lo más importante, conocer los hallazgos radiológicos de las distintas lesiones. La prueba de imagen inicial en la mayoría de los pacientes será la ecografía abdominal simple, siendo a veces necesario completar el estudio con resonancia magnética o tomografía computarizada. El estudio histológico se llevará a cabo en lesiones con características atípicas o datos que orienten a malignidad. Aunque la mayoría de las lesiones hepáticas son benignas, algunas están asociadas a enfermedades sistémicas o a hepatopatía crónica, siendo necesario manejarlas en unidades multidisciplinares especializadas.
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- 2024
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15. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study
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Zajac, S R, Bley, M V, Scazufca, A, Rosateli, P, Reis, T, Junior, A Nogueira, Neto, P A Nunes, Filho, I L S, Lima, H, Vieira, M, Zanchet, M, Ferreira, I, Miguita, R, Petisco, G M, Westphal, G A, Santos, J R P, Damasceno, V, dos Santos, J T, Fernandes, F, Almeida, EP, Lemos, M, Lima, M F A, Camacho, R, Ribeiro, A, Douglas, M O G, Mattei, G A, Junior, E A, Ferreira, P, Rabelo, H R M P, Pinto, S P S, Fontes, L E, Machado, D, Guitzel, M, Lucio, M, Conceição, C N P, Barros, A, Salgado, D, Veiga, V C, Rojas, S S O, de Paula, KM, Hatum, R, Fraenkel, L, Viana, W N, Santos, A P G, Rabello, L, Tanaka, L, Uchoa, M, Moura, M D, Gneco, H, Buarque, M F, Monteiro, K, Nassar, A P, Jr, Koterba, E, Teixeira, M J, Falcão, A L E, Pinto, V G S, Junior, J M M, Gut, A L, Stefano, L M, Damasceno, M, Lontra, M V, Cozzani, C, Sobrinho, E B, Lage, S G, Kopel, L, Youssef, N C M, Sanches, L C, Amendola, C P, Kmohan, C, Silva, C B, Schifelbain, L, Bellotto, E, Viecili, P, Azevedo, L, Monteiro, L, Vieira, S, Abrão, A M, Moraes, A P, Insaurrale, H, Gadelha, M, Marisa, D, Diniz, R N, Romano, E R, Luzzi, S, Rezende, E, Filho, M C, Martins, R H F C, Carvalho, F B, Moreira, G C, Paula, J, Haag, F, Jr, Lucena, FS, Machado, R S, Filho, W O, Cavalcante, L O, Filho, H Carvalho, Lima, G S, Trombka, J N, Machado, E C, Bainy, M P, Ramos, C H, Hoppe, C, Luckmeyer, G D, Vogas, C, Thompson, M M, Sousa, R K, Fernandes, R, Lourenço, E, Peixoto, G L, Mocelin, A, Silva, M M L, Neto, J S A, Villela, C, Mendonça, S L, Prado, S C, Goulart, R, Duarte, J J L, Junior, H A O, Andrade, J N, Souza, L F, Fernandes, L, Neto, M L, Fernandes, S S, Amâncio, F, Versiani, J C, Pitanga, F, Alcantara, M B, Reiff, C C, Rosenblat, R, Nobrega, M S, Nobrega, M L F S, Costa, G, Assunção, N, Almeida, E P, Neder, L, Almeida, R, Fuck, J, Souza, R M, Ribeiro, A G, Alves, A A G, Carvalho, S H C, Arbex, M, Oliveira, E C, Melo, R S, Conde, K, Abreu, N Q, Melo, C L T, Carvalho, A A, Lannes, R, Missaka, H, Furtado, A H, Jr, Peixoto, A A, Jr, Maia, I, Pincelli, M P, Yunes, M P, Pessoa, A N, Figueiredo, S, Botoni, F A, Cunha, C T, Olson, F A, Franco, R, Bemfica, A F, Junior, A D F, Ferreira, E L A, Messeder, O, Passos, R, Lira, J A, Vilela, C A, Junior, S M D, Ferreira, C S, Muller, O P J A, dos Santos, R Perreira, Rubini, P, Monteiro, D, Rodrigues, L E, Ruivo, G F, Gomes, M C, Egito, E, Assef, M G, Lima, M A M, Borges, A F, Jezler, S, Mendes, C, Gottardo, P C, Lima, R, Filho, C M F, Campagnucci, V P, Solino, I, Lorca, A P, Rodrigues, G M, Gerent, K B, Barbosa, O, Filho, G T Henriques, Troncoso, E, Ventura, A, Silva, M A, Houly, J G, Pimentel, J P M, Ramos, R A, Gianini, F, Casemiro, B, Pinto, E M, Silva, G A, Sebold, M, Vieira, E, Ferreira, R, Gomes, L A, Lovato, W J, Dantas, W, Ishy, L, Moreira, J, Gagliardi, I, Goes, L O, Vendrame, L S, Guimarães, H P, Gois, A, Machado, F R, Rodrigues, M, Jr, Vieira, P C B, Bittencourt, W, Melnick, E, Schneider, M, Rezegue, L, Nogueira, N J M, Godinho, E P, Mazza, B F, Paciencia, L E, Ferraz, S, Imamura, C R A, Tavares, J, Santos, J C, Vale, E, Filho, J Mugait, Tannous, L A, João, P G D, Geral, C T I, Matera, A P, Matsui, M, Neto, E Eberhart, Pinheiro, B V, Carvalho, E V, Matos, H, Lippi, M, Campos, A L, Albuquerque, D C, Castiglioni, D, Silva, G S, Cunha, S, Novello, E, Silva, M E B, Grion, C, Festti, J, Souza, C R A, Mecatti, G C, Junqueira, E B, Dutra, R S, Mirachi, G B, Mendes, D A, Moura, E M F, Silva, I F, Mota, M G P, Carneiro, T, Celso, A, Réa-Neto, A, Oliveira, M C, Japiassú, A, Castro, P P, Costa, H J M, Rolim, A V, Rocha, D, Righy, C, Santos, V, Fernandino, B, Pereira, A L, Rego, V L D, Melo, L A, Guilherme, L, Ferro, H Chagas, Silva, F J L, Carrasco, H V C J, El-Fakouri, S, Alvarez, J, de Castro, D, Shiavetto, P M, Gallate, S R, Filho, E Thomé, Veneziano, S G, Antoniazzi, P, Filho, W H, Sadala, P, Balbino, C, Moreno, G, Dias, M S F, Lopez, R P, Rodrigues, M L, Terceiro, J, Serpa, M F, Santos, L, Lippi, M M, Machado, Flavia R, Cavalcanti, Alexandre Biasi, Bozza, Fernando Augusto, Ferreira, Elaine M, Angotti Carrara, Fernanda Sousa, Sousa, Juliana Lubarino, Caixeta, Noemi, Salomao, Reinaldo, Angus, Derek C, and Pontes Azevedo, Luciano Cesar
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- 2017
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16. Early circulating tumour DNA kinetics measured by ultra-deep next-generation sequencing during radical radiotherapy for non-small cell lung cancer: a feasibility study
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Walls, G. M., McConnell, L., McAleese, J., Murray, P., Lynch, T. B., Savage, K., Hanna, G. G., and de Castro, D. Gonzalez
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- 2020
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17. Morphotectonic development of the Ceará Terrace: a marginal ridge on the western side of the Romanche Fracture Zone in the Brazilian Equatorial Margin
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Andrade, João Fernando Pezza, Gomes, M. P., Bezerra, F. H. R., de Castro, D. L., and Vital, H.
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- 2018
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18. Prolonged electrocardiographic monitorization with a wearable system after an embolic stroke of undetermined source
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De Castro, D, primary, Jorge Toquero, J T R, additional, Diego Jimenez, D J S, additional, Eusebio Garcia-Izquierdo, E G I, additional, Victor Castro-Urda, V C U, additional, Cristina Aguilera-Agudo, C A A, additional, Daniel Garcia-Rodriguez, D G R, additional, Fernando Hernandez-Terciado, F H T, additional, Paula Vela-Martin, P V M, additional, Paloma Remior, P R P, additional, Andrea Matutano, A M M, additional, Ramon Garrido-Gonzalez, R G G, additional, Daniel Escribano Garcia, D E G, additional, Sergio Garcia-Gomez, S G G, additional, and Ignacio Fernandez-Lozano, I F L, additional
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- 2023
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19. EuroClonality-NGS Recommendations for Evaluation of B-Cell Clonality Analysis by Next-Generation Sequencing: A Structured Approach with the DEPART Algorithm.
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Brand, M. van den, Möbs, M., Otto, F., Kroeze, L.I., Gonzalez de Castro, D., Stamatopoulos, K., Davi, F., Bravetti, C., Kolijn, P.M., Vlachonikola, E., Stewart, J.P., Pott, C., Hummel, M., Darzentas, N., Langerak, A.W., Fend, F., Groenen, P.J.T.A., Brand, M. van den, Möbs, M., Otto, F., Kroeze, L.I., Gonzalez de Castro, D., Stamatopoulos, K., Davi, F., Bravetti, C., Kolijn, P.M., Vlachonikola, E., Stewart, J.P., Pott, C., Hummel, M., Darzentas, N., Langerak, A.W., Fend, F., and Groenen, P.J.T.A.
- Abstract
Contains fulltext : 296673.pdf (Publisher’s version ) (Open Access), Next-generation sequencing (NGS)-based clonality analysis allows in-depth assessment of the clonal composition of a sample with high sensitivity for detecting small clones. Within the EuroClonality-NGS Working Group, a protocol for NGS Ig clonality analysis was developed and validated previously. This NGS-based approach was designed to generate small amplicons, making it suitable for samples with suboptimal DNA quality, especially material derived from formalin-fixed, paraffin-embedded tissue. Using expert assessment of NGS Ig clonality results as a reference, a structured algorithmic approach to the assessment of NGS-amplicon-based B-cell clonality analysis was developed. A structured approach with the Detection of clonality through Evaluation of sample quality and assessment of Pattern, Abundance and RaTio (DEPART) algorithm was proposed, which consecutively evaluates sample quality, the pattern of the clonotypes present, the abundance of the most dominant clonotypes, and the ratio between the dominant clonotypes and the background to evaluate the different Ig gene targets. Specific issues with respect to evaluation of the various Ig targets as well as the integration of results of individual targets into a molecular clonality conclusion are discussed and illustrated with case examples. Finally, the importance of interpretation of NGS-based clonality results in clinical and histopathologic contexts is discussed. It is expected that these recommendations will have clinical utility to facilitate proper evaluation of clonality assessment.
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- 2023
20. Creep strength boosted by a high-density of stable nanoprecipitates in high-chromium steels
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Vivas, J., De-Castro, D., Poplawsky, J. D., (0000-0002-1177-2650) Altstadt, E., Houska, M., Urones-Garrote, E., San Martín, D., Caballero, F. G., Serrano, M., Capdevila, C., Vivas, J., De-Castro, D., Poplawsky, J. D., (0000-0002-1177-2650) Altstadt, E., Houska, M., Urones-Garrote, E., San Martín, D., Caballero, F. G., Serrano, M., and Capdevila, C.
- Abstract
there is a need worldwide to develop materials for advanced power plants with steam temperatures of 700°c and above that will achieve long-term creep-rupture strength and low cO2 emissions. the creep resistance of actual 9-12cr steels is not enough to fulfil the engineering requirements above 600°c. in this paper, the authors report their advances in the improvement of creep properties of this type of steels by the microstructural optimization through nano-precipitation using two methodologies. 1) Applying a high temperature austenitization cycle followed by an ausforming step (thermomechanical treatment, tMt ) to G91 steel, to increase the martensite dislocation density and, thus, the number density of MX precipitates (M = v,Nb; X = c,N) but at the expense of deteriorating the ductility. 2) compositional adjustments, guided by computational thermodynamics, combined with a conventional heat treatment (no tMt ), to design novel steels with a good ductility while still possessing a high number density of MX precipitates, similar to the one obtained after the tMt in G91. the microstructures have been characterized by optical, scanning and transmission electron microscopy, eBSD and atom probe tomog- raphy. the creep behaviour at 700°c has been eval- uated under a load of 200 N using small punch creep tests.
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- 2023
21. The Mesozoic Equatorial Atlantic Magmatic Province (EQUAMP)
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Hollanda, M. H. B. M., primary, Archanjo, C. J., additional, Macedo Filho, A. A., additional, Fossen, H., additional, Ernst, R. E., additional, de Castro, D. L., additional, Melo, A. C., additional, and Oliveira, A. L., additional
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- 2018
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22. The eBADGE approach to an intelligent pan-European balancing mechanism
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Zani, A., Migliavacca, G., Nemcek, P., Auer, H., Burnier de Castro, D., and Esterl, T.
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- 2015
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23. Telomere length predicts progression and overall survival in chronic lymphocytic leukemia: data from the UK LRF CLL4 trial
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Strefford, J C, Kadalayil, L, Forster, J, Rose-Zerilli, M J J, Parker, A, Lin, T T, Heppel, N, Norris, K, Gardiner, A, Davies, Z, Gonzalez de Castro, D, Else, M, Steele, A J, Parker, H, Stankovic, T, Pepper, C, Fegan, C, Baird, D, Collins, A, Catovsky, D, and Oscier, D G
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- 2015
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24. Creep strength boosted by a high-density of stable nanoprecipitates in high-chromium steels
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Vivas, J., primary, De-Castro, D., additional, Poplawsky, J. D., additional, Altstadt, E., additional, Houska, M., additional, Urones-Garrote, E., additional, San-Martín, D., additional, Caballero, F.G., additional, Serrano, M., additional, and Capdevila, C., additional
- Published
- 2022
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25. Effect of processing parameters on texture and variant selection of as-built 300 maraging steel processed by laser powder bed fusion
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Ministerio de Economía y Competitividad (España), Eres-Castellanos, Adriana, Santana, A., De-Castro, D., Jiménez, José Antonio, Rementería, Rosalía, Capdevila, Carlos, García Caballero, Francisca, Ministerio de Economía y Competitividad (España), Eres-Castellanos, Adriana, Santana, A., De-Castro, D., Jiménez, José Antonio, Rementería, Rosalía, Capdevila, Carlos, and García Caballero, Francisca
- Abstract
Among the materials that might be manufactured with laser powder bed fusion (LPBF), one can highlight maraging steels, with excellent weldability, strength and fracture toughness. However, the effects of the processing parameters and the mechanisms governing the as-built texture are not clear yet. A recent publication showed a low texture index in the prior austenite, in contrast to other alloys subjected to LPBF with the same strategy. Authors suggested several hypotheses, although no conclusions were drawn. This work aims to investigate these findings by using a 300 maraging steel processed under different conditions, i.e. different printer, powder layer thickness and laser emission mode. To do so, X-Ray Diffraction, Electron Backscattered Diffraction and Scanning Electron Microscopy have been used. Results show that the heat treatment intrinsic to the LPBF process does not affect the prior austenite grains, whose texture and morphology remain unchanged throughout the process. Also, for the studied ranges, the microstructure texture is not related to the powder layer thickness or to the laser emission mode, although it could be affected by the laser power or the scan strategy. Finally, a low degree of variant selection has been observed, where the selected variants are those that contribute to a martensite cubic rotated texture.
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- 2022
26. Creep strength boosted by a high-density of stable nanoprecipitates in high-chromium steels
- Author
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Agencia Estatal de Investigación (España), Ministerio de Economía, Industria y Competitividad (España), Vivas, J., De-Castro, D., Poplawsky, Jonathan D., Altstadt, E., Houska, M., Urones-Garrote, E., San-Martín, David, García Caballero, Francisca, Serrano, M., Capdevila, Carlos, Agencia Estatal de Investigación (España), Ministerio de Economía, Industria y Competitividad (España), Vivas, J., De-Castro, D., Poplawsky, Jonathan D., Altstadt, E., Houska, M., Urones-Garrote, E., San-Martín, David, García Caballero, Francisca, Serrano, M., and Capdevila, Carlos
- Abstract
There is a need worldwide to develop materials for advanced power plants with steam temperatures of 700 °C and above that will achieve long-term creep-rupture strength and low CO2 emissions. The creep resistance of actual 9-12Cr steels is not enough to fulfil the engineering requirements above 600 °C. In this paper, the authors report their advances in the improvement of creep properties of this type of steels by the microstructural optimization through nano-precipitation using two methodologies. 1) Applying a high temperature austenitization cycle followed by an ausforming step (thermomechanical treatment, TMT) to G91 steel, to increase the martensite dislocation density and, thus, the number density of MX precipitates (M = V,Nb; X = C,N) but at the expense of deteriorating the ductility. 2) Compositional adjustments, guided by computational thermodynamics, combined with a conventional heat treatment (no TMT), to design novel steels with a good ductility while still possessing a high number density of MX precipitates, similar to the one obtained after the TMT in G91. The microstructures have been characterized by optical, scanning and transmission electron microscopy, EBSD and atom probe tomography. The creep behaviour at 700 °C has been evaluated under a load of 200 N using small punch creep tests.
- Published
- 2022
27. Morphological and crystallographic features of granular and lath-like bainite in a low carbon microalloyed steel
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European Coal and Steel Community, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), De-Castro, D., Eres-Castellanos, Adriana, Vivas, J., García Caballero, Francisca, San-Martín, David, Capdevila, Carlos, European Coal and Steel Community, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), De-Castro, D., Eres-Castellanos, Adriana, Vivas, J., García Caballero, Francisca, San-Martín, David, and Capdevila, Carlos
- Abstract
In this work, different heat treatments were performed in order to study two different bainite morphologies, granular and lath-like, obtained at different cooling rates in a low carbon microalloyed steel. For that purpose, advanced crystallographic characterization and quantitative metallography using SEM, EBSD and TEM were carried out. The evolution of the volume percentage, size, aspect ratio, retained austenite volume percentage and crystallography of the M/A constituents was studied as a function of the cooling rate and classified according to a machine learning algorithm. For the characterization of the crystallography and morphology of the bainitic ferrite matrix, two microstructures were selected as representative of granular and lath-like bainite. The results show that the main differences between granular and lath-like bainite are the size and shape of the M/A constituents, that change progressively from a mixture of large grains, coarse blocks and fine roughly equiaxed grains at low cooling rates to short and long films at high cooling rates. The crystallographic and morphological differences between both microstructures can be explained based on the different driving force and amount of bainitic ferrite formed at the different temperature ranges. These results confirm that the mechanisms by which granular bainite forms are not different from the transformation mechanisms of lath-like bainite.
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- 2022
28. Organization of Respiratory Reflexes in the Caudal Region of the Nucleus of the Tractus Solitarius
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Housley, G. D., Brew, S., de Castro, D., Sinclair, J. D., Koepchen, Hans-Peter, editor, and Huopaniemi, Timo, editor
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- 1991
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29. The Role of Glutamate in the Transmission of the Hypoxic Input to Respiration Through the Nucleus of the Tractus Solitarius
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Brew, S., de Castro, D., Housley, G. D., Sinclair, J. D., Acker, Helmut, editor, Trzebski, Andrzej, editor, and O’Regan, Ronan G., editor
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- 1990
- Full Text
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30. Sex differences in implantable cardiac defibrillator decision: myth or fact?
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Remior, P, primary, Garcia-Rodriguez, D, additional, Aguilera-Agudo, C, additional, Garcia-Izquierdo, E, additional, Jimenez-Sanchez, D, additional, Castro-Urda, V, additional, Garcia-Gomez, S, additional, Pham-Trung, C, additional, De Castro, D, additional, Veloza-Urrea, D, additional, Morillo, J, additional, Fernandez-Lozano, I, additional, and Toquero-Ramos, J, additional
- Published
- 2021
- Full Text
- View/download PDF
31. Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial
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Sclafani, F., Chau, I., Cunningham, D., Peckitt, C., Lampis, A., Hahne, J.C., Braconi, C., Tabernero, J., Glimelius, B., Cervantes, A., Begum, R., Gonzalez De Castro, D., Hulkki Wilson, S., Eltahir, Z., Wotherspoon, A., Tait, D., Brown, G., Oates, J., and Valeri, N.
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- 2015
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32. CELL‐FREE DNA KINETICS DECIPHER POTENTIAL MECHANISMS OF ACTION OF IBRUTINIB COMBINATION THERAPY IN MANTLE CELL LYMPHOMA (MCL).
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Khouja, M., Genuardi, E., Ferrero, S., Alessandria, B., Verhagen, O. J., Homburg, C., van der Velden, V. H., Gameiro, P., Sanz, R. García, Herrera, A. Medina, Fronkova, E., Brüggemann, M., Dreyling, M., Hoster, E., Ladetto, M., Langerak, A. W., Darzentas, N., Pal, K., Stewart, P. J., and Gonzalez de Castro, D.
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CELL-free DNA ,CIRCULATING tumor DNA ,TUMOR genetics ,CELLULAR therapy ,MANTLE cell lymphoma ,SINGLE nucleotide polymorphisms - Abstract
Cell-free (cf)DNA captures tumor genetics and can be used to assess disease kinetics and minimal residual disease (MRD). B Introduction: b The European MCL Network trial TRIANGLE (NCT02858258) evaluated the addition of ibrutinib to standard treatment with autologous stem cell transplantation (ASCT) (arm A+I) in comparison to ASCT alone (arm A) and ibrutinib plus chemoimmunotherapy without ASCT (arm I) demonstrating significant and clinically relevant superiority of additional ibrutinib on outcome. CELL-FREE DNA KINETICS DECIPHER POTENTIAL MECHANISMS OF ACTION OF IBRUTINIB COMBINATION THERAPY IN MANTLE CELL LYMPHOMA (MCL). [Extracted from the article]
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- 2023
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33. EEN EN ANDER OVER GLASGRAVURE
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DE CASTRO, D. HENRIQUES
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- 1883
34. PO-1124 Is there a role for bolus in the modern era of breast cancer treatments? A retrospective analysis.
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Félix Penido Mendes de Sousa, C., primary, Jenwei Chen, M., additional, Joffily Pinto, P.J., additional, Favareto, S.L., additional, Ko Chen, F., additional, Humeres Abrahão, C., additional, Guedes de Castro, D., additional, Santos Neto, E., additional, Ramos, H., additional, Gobo Silva, M.L., additional, Fogaroli, R.C., additional, Assis Pellizzon, A.C., additional, and Rocha Melo Gondim, G., additional
- Published
- 2021
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35. Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns
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Moore, A S, Faisal, A, de Castro, D Gonzalez, Bavetsias, V, Sun, C, Atrash, B, Valenti, M, de Haven Brandon, A, Avery, S, Mair, D, Mirabella, F, Swansbury, J, Pearson, A D J, Workman, P, Blagg, J, Raynaud, F I, Eccles, S A, and Linardopoulos, S
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- 2012
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36. Integrated geophysical approach for detection and size-geometry characterization of a multiscale karst system in carbonate units, semiarid Brazil
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de Castro David L., Bezerra Francisco H. R., and Oliveira Jr Josibel G.
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karst ,fracture corridor ,ghost-rock ,cave system ,geophysical data ,multiscale investigation ,Geology ,QE1-996.5 - Abstract
The karstification of carbonate rocks creates 3D maze voids that are normally controlled by fracture networks and sedimentary bedding. The spatial distribution and density of karst systems are usually complex and difficult to predict, demanding multidisciplinary studies at different scales of investigation to determine the spatial distribution and density of karst features and their possible links with cave systems controlled by the regional structural setting. The present study integrates geophysical datasets (gravity, electrical resistivity tomography - ERT, and ground penetrating radar - GPR) with a digital elevation model to investigate a karst system in the Irecê basin, a semiarid region of Brazil. Morphostructural lineaments reveal a NNW-SSE- and E-W-oriented structural setting of the crystalline basement, which is imprinted on the internal basin architecture, and surface drainage network. Negative gravity anomalies and high-gradient gravity zones indicate the main karstic zone, where karst landforms are concentrated. In addition, 2.5D gravity modeling provides the internal basin geometry, demonstrating that the karst system has evolved in the thickest sector of the basin. ERT profiles delineate the underground passages that connect dolines at depth. Finally, GPR data image shallow subsurface ghost-rock karstification that spread out from the surface to depth and that took advantage of vertical fractures and slightly arched bedding planes. Our results point out the role of the fracture corridors in channelizing hydrodynamic energy at a sufficiently high level to create caves by the total removal of dissolved material, whereas in the surrounding areas under low hydrodynamic conditions, overall shallow ghost-rock karstification took place, creating residual weathered rocks (alterites).
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- 2024
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37. A novel translocation, t(14;19)(q32;p13), involving IGH@ and the cytokine receptor for erythropoietin
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Russell, L J, De Castro, D G, Griffiths, M, Telford, N, Bernard, O, Panzer-Grümayer, R, Heidenreich, O, Moorman, A V, and Harrison, C J
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- 2009
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38. HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab
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Sclafani, F., Roy, A., Cunningham, D., Wotherspoon, A., Peckitt, C., Gonzalez de Castro, D., Tabernero, J., Glimelius, B., Cervantes, A., Eltahir, Z., Oates, J., and Chau, I.
- Published
- 2013
- Full Text
- View/download PDF
39. Analysis of KRAS, NRAS, BRAF, PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients
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Sclafani F, Hulkki Wilson S, Cunningham D, Gonzalez De Castro D, Kalaitzaki E, Begum R, Wotherspoon A, Capdevila J, Glimelius B, Rosello S, Thomas J, Tait D, Brown G, Oates J, and Chau I
- Subjects
endocrine system diseases ,KRAS ,NRAS ,PIK3CA ,TP53 ,rectal cancer ,neoplasms ,BRAF - Abstract
Little information is available on the clinical significance of cancer-related genes such as KRAS, NRAS, BRAF, PIK3CA and TP53 in nonmetastatic rectal cancer. We investigated mutations of these genes in a large prospective series of locally advanced rectal cancer (LARC) patients who were recruited into two phase II trials. Mutational analyses were performed with diagnostically validated methods including polymerase chain reaction, capillary electrophoresis single-strand conformational analysis, Sanger sequencing and next-generation sequencing. Associations between single or multiple gene mutations and clinicopathological characteristics and treatment outcomes were explored. Of these 269, 210 (78%) patients were assessable. Mutations of KRAS, NRAS, BRAF, PIK3CA and TP53 occurred in 43, 9, 4, 9 and 60% of patients, respectively. Concordance between paired biopsy and resection specimens was 82% for KRAS, 95% for NRAS, 99% for BRAF, 96% for PIK3CA and 63% for TP53. TP53 mutations were associated with extramural venous invasion on baseline MRI (78% vs. 65%, p = 0.04), poor pathological tumour regression (23% vs. 36%, p = 0.05) and a trend toward a worse 5-year progression-free survival (PFS; 60% vs. 74%, HR 1.59, p = 0.06). Patients with tumours harbouring mutation of TP53 and either KRAS or NRAS (32%) had a worse 5-year PFS than those with TP53/KRAS/NRAS wild-type tumours (54% vs. 72%, HR 1.75, p = 0.02). In univariate analysis, BRAF mutation predicted poor 5-year overall survival only among patients treated without cetuximab (20% vs. 73%, HR 3.29, p = 0.03). This is one of the largest biomarker studies in a prospective, largely homogeneous, LARC population. Our findings are hypothesis generating and require validation in independent series.
- Published
- 2020
40. Early circulating tumour DNA kinetics measured by ultra-deep next-generation sequencing during radical radiotherapy for non-small cell lung cancer: a feasibility study
- Author
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Walls, GM, McConnell, L, McAleese, J, Murray, P, Lynch, TB, Savage, K, Hanna, GG, Gonzalez de Castro, D, Walls, GM, McConnell, L, McAleese, J, Murray, P, Lynch, TB, Savage, K, Hanna, GG, and Gonzalez de Castro, D
- Abstract
BACKGROUND: The evaluation of circulating tumour DNA (ctDNA) from clinical blood samples, liquid biopsy, offers several diagnostic advantages compared with traditional tissue biopsy, such as shorter processing time, reduced patient risk and the opportunity to assess tumour heterogeneity. The historically poor sensitivity of ctDNA testing, has restricted its integration into routine clinical practice for non-metastatic disease. The early kinetics of ctDNA during radical radiotherapy for localised NSCLC have not been described with ultra-deep next generation sequencing previously. MATERIALS AND METHODS: Patients with CT/PET-staged locally advanced, NSCLC prospectively consented to undergo serial venepuncture during the first week of radical radiotherapy alone. All patients received 55Gy in 20 fractions. Plasma samples were processed using the commercially available Roche AVENIO Expanded kit (Roche Sequencing Solutions, Pleasanton, CA, US) which targets 77 genes. RESULTS: Tumour-specific mutations were found in all patients (1 in 3 patients; 2 in 1 patient, and 3 in 1 patient). The variant allele frequency of these mutations ranged from 0.05-3.35%. In 2 patients there was a transient increase in ctDNA levels at the 72 h timepoint compared to baseline. In all patients there was a non-significant decrease in ctDNA levels at the 7-day timepoint in comparison to baseline (p = 0.4627). CONCLUSION: This study demonstrates the feasibility of applying ctDNA-optimised NGS protocols through specified time-points in a small homogenous cohort of patients with localised lung cancer treated with radiotherapy. Studies are required to assess ctDNA kinetics as a predictive biomarker in radiotherapy. Priming tumours for liquid biopsy using radiation warrants further exploration.
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- 2020
41. Design and high temperature behavior of novel heat resistant steels strengthened by high density of stable nanoprecipitates
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(0000-0002-5364-733X) Vivas, J., De-Castro, D., (0000-0002-1177-2650) Altstadt, E., Houska, M., (0000-0001-6720-3599) San-Martin, D., (0000-0002-1869-4085) Capdevila, C., (0000-0002-5364-733X) Vivas, J., De-Castro, D., (0000-0002-1177-2650) Altstadt, E., Houska, M., (0000-0001-6720-3599) San-Martin, D., and (0000-0002-1869-4085) Capdevila, C.
- Abstract
International efforts have been focused on the development of new 9Cr Ferritic/Martensitic steels capable of operating at temperatures above 700 ºC to improve thermal efficiency of new power plants. The distribution and size of the MX nanoprecipitates present in these steels have been reported to be the key factor for improving the thermal stability of the microstructure during creep. Bearing in mind these findings, three different heat resistant steels were designed to have a higher number density of MX nanoprecipitates than commercial 9Cr ferritic/martensitic steels. The manufacturing and subsequent microstructural characterization carried out showed that this goal was achieved. Preliminary high temperature strength results performed by means of Small Punch Creep Tests (SPCT) demonstrated that these new steels improve significantly the high temperature strength without an important loss of ductility as compared to a current commercial 9Cr Ferritic/Martensitic steel.
- Published
- 2020
42. The relationship between deficit in digit span and genotype in nonsense mutation Duchenne muscular dystrophy
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Thangarajh, M, Elfring, GL, Trifillis, P, McIntosh, J, Peitz, SW, Ryan, MM, Kornberg, AJ, RodriguezCasero, V, Wray, A, Jones, KJ, North, K, Goemans, N, Buyse, GM, Campbell, C, Mah, J, Sarnat, H, Selby, K, Voit, T, Doppler, V, De Castro, D, Chabrol, B, Levy, N, Halbert, C, Pereon, Y, Magot, A, Perrier, J, Mahe, JY, Schara, U, Lutz, S, Busse, M, Della Marina, A, Kirschner, J, Stanescu, A, Pohl, A, RensingZimmerman, C, Bertini, E, D'Amico, A, Kofler, A, Carlesi, A, Bonetti, AM, Santecchia, L, Emma, F, Bergami, G, Mercuri, EM, Vasco, G, Bianco, F, Mazzone, ES, De Sanctis, R, Alfieri, P, Pane, M, Messina, S, Comi, GP, Magri, F, Lucchini, V, Corti, SP, Moggio, MG, Sciacco, M, Bresolin, N, Prelle, AC, Magri, R, Virgilio, R, Lamperti, C, Nevo, Y, DorWollman, T, Vilchez, J, Muelas, N, Sevilla, T, Smeyers, P, de la Osa, A, Colomer, J, Ortez, CI, Nascimento, A, Febrer, A, Medina, J, Tulinus, M, Thorarinsdottir, B, Darin, N, Sejersen, T, Hovmoller, M, Bushby, K, Straub, V, Guglieri, M, Sarkozy, A, Willis, T, Eagle, M, Mayhew, A, Muntoni, F, Cirak, S, Manzur, AY, Robb, SA, Kinali, M, Quinlivan, RCM, Smith, MR, Pandey, R, Wong, B, Collins, J, Finkel, R, Bonnemann, C, Yang, M, Foley, AR, Yum, S, Sampson, J, Bromberg, M, Swoboda, K, Day, J, Karachunski, P, Mathews, K, Bonthius, D, Laubenthal, KS, Darras, B, Kang, P, Parson, J, Barohn, R, Dasouki, M, Anderson, H, Burns, J, Dimachkie, M, Pasnoor, M, Wang, YX, Ciafaloni, E, Heatwole, C, Connolly, A, Pestronk, A, Al-Lozi, M, Lopate, G, Golumbek, P, Sommerville, B, Wang, L, Wojcicka-Mitchell, A, Godbey, A, Harms, M, Varadachary, A, Iyadurai, S, Rojas, L, Iannacone, S, Khonghatithum, C, Sproule, D, De Vivo, D, Constantinescu, A, McDonald, C, Han, J, Ben Renfroe, Russman, B, Sussman, M, BurnsWechsler, S, Juel, V, Hobson-Webb, L, Smith, E, Ataluren Phase 2b Study Grp, Schara, Ulrike (Beitragende*r), and Marina, Adela Della (Beitragende*r)
- Subjects
Male ,0301 basic medicine ,Adolescent ,Duchenne muscular dystrophy ,Nonsense mutation ,Medizin ,Neuropsychological Tests ,030105 genetics & heredity ,Article ,Young Adult ,03 medical and health sciences ,Exon ,Settore MED/39 - NEUROPSICHIATRIA INFANTILE ,0302 clinical medicine ,Genotype ,Memory span ,medicine ,Humans ,Child ,Genetics ,biology ,Promoter ,Duchenne ,medicine.disease ,Muscular Dystrophy, Duchenne ,Cross-Sectional Studies ,Memory, Short-Term ,Codon, Nonsense ,Child, Preschool ,Mutation (genetic algorithm) ,biology.protein ,Neurology (clinical) ,Dystrophin ,030217 neurology & neurosurgery - Abstract
ObjectiveTo evaluate the relationship between deficit in digit span and genotype in nonsense mutation (nm) Duchenne muscular dystrophy (DMD) (nmDMD).MethodsWe investigated the relationship between normalized digit-span forward (d-sf) and digit-span backward (d-sb) scores to the location of nmDMD mutations in 169 participants ≥5 to ≤20 years who participated in a phase 2b clinical trial. Because alternative promoters are found upstream of DMD exons 30, 45, and 63, we correlated d-sf and d-sb to the specific nmDMD mutation location.ResultsParticipants with nm downstream of exon 30, downstream of exon 45, and downstream of exon 63 had significantly lower normalized d-sf scores (p < 0.0001). Participants with nm downstream of exon 45 in addition had significantly lower normalized d-sb score (p < 0.04). There was no significant difference in the normalized d-sb score in participants with mutations upstream or downstream of DMD exon 30 or upstream or downstream of DMD exon 63.ConclusionOur data provide evidence that specific cognitive deficits correlate to genotype in individuals with nmDMD, highlighting the critical role of brain-specific dystrophin isoforms in the neurobiological manifestations of this disease.Clinicaltrials.gov identifierNCT02090959.
- Published
- 2018
43. Testing international techniques for the radiographic assessment of third molar maturation
- Author
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Sartori, V., primary, Franco, A., additional, Linden, M., additional, Cardoso, M., additional, de Castro, D., additional, Sartori, A., additional, Silva, C., additional, Trentin, M., additional, and De Carli, J., additional
- Published
- 2021
- Full Text
- View/download PDF
44. Personalized Cancer Medicine: Molecular Diagnostics, Predictive Biomarkers, and Drug Resistance
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Gonzalez de Castro, D, Clarke, P A, Al-Lazikani, B, and Workman, P
- Published
- 2013
- Full Text
- View/download PDF
45. Geological and geotechnical conditions of human interventions in natural volcanic caverns
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Olalla, C, primary, Cárdenas, A, additional, Serrano, A, additional, Pradera, E, additional, and de Castro, D, additional
- Published
- 2010
- Full Text
- View/download PDF
46. Discordant results using T-ARMS-PCR and sequencing for the evaluation of rs12979860 IL28B genotype
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de Sa Filho, D. J., de Castro, D. F., Gagliani, L. H., and Caseiro, M. M.
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- 2012
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47. Examining the multi-scale complexity and the crystallographic hierarchy of isothermally treated bainitic and martensitic structures
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De-Castro, D., primary, Rementeria, R., additional, Vivas, J., additional, Sourmail, T., additional, Poplawsky, J.D., additional, Urones-Garrote, E., additional, Jimenez, J.A., additional, Capdevila, C., additional, and Caballero, F.G., additional
- Published
- 2020
- Full Text
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48. Complex ferritic structures obtained by three different heat treatments: differences and similarities
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De Castro, D., Rementería, Rosalía, Sourmail, Thomas, Poplawsky, Jon D., Vivas, Javier, Capdevila, Carlos, and García Caballero, Francisca
- Subjects
Quenching and partitioning (Q&P) ,TRIP steels ,Strength steels ,Martensite ,Austenite - Abstract
EUROMAT 2019 - B: Structural Materials, Recently, a new processing concept known as quenching and partitioning (Q&P) has been proposed for designing high strength steels. This process involves quenching austenite below the martensite-start temperature, followed by a partitioning treatment to enrich the remaining austenite with carbon, thereby stabilizing it to room temperature. The resultant microstructures mainly consist of tempered martensite and retained austenite so that a higher strength can be achieved as compared to conventional TRIP steels. In high silicon hypereutectoid steels, lath-like ferrite matrix and a significant amount of ductile austenite that improves the work-hardening of the complex composite structure by TRIP effect can be also achieved by more conventional heat treatments such as an isothermal bainite treatment (B) or a traditional quench and temper (Q&T).
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- 2019
49. Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA
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McGuire D, Alexander J, Johansen O, Perkovic V, Rosenstock J, Cooper M, Wanner C, Kahn S, Toto R, Zinman B, Baanstra D, Pfarr E, Schnaidt S, Meinicke T, George J, von Eynatten M, Marx N, Aizenberg D, Fiorella A, Edgardo N, Belen C, Alonso P, Walter M, Maia K, Guillermo S, Leandro B, Constanza R, Alejandra N, Melina C, Ariel I, Rodrigo C, Alvarez C, Jorge M, Gabriel C, German S, Bartolacci I, Bolobanich G, Tale T, Meritano M, Echeverria M, Gerrini S, Alvarez M, Torrijos N, Berli M, Coggiola J, Castaneda G, Rode R, Milessi R, Roude A, Bono J, Caresani J, Arias V, Westberg J, Allende G, Liberman A, Bordonava A, Almagro S, Gerbaudo C, Schiavi L, Budassi N, Cecilia M, Buncuga M, Carlos S, Osvaldo T, Mercedes S, Calella P, Agustina V, Aljandro M, Alberto D, Fiorella M, Cantero M, Cariganano M, Anadon P, Cartasegna L, Gabriela M, Fernanda A, Alberto R, Chacon C, Jazmin F, Colombo H, Coni E, Mattausch S, Thomsenhall K, della Torre M, Morandini M, Berra F, Margarita H, Commendatore V, Tedesco J, Bolzan P, Cuneo C, Narcisa G, Caputi V, Pablo S, Sandra G, Pacora F, Tinari M, Jure H, Parody M, Toranzo A, Frechtel G, Yohena S, Lovecchio S, Muller C, Martin S, Olivera C, Breyaui M, Bianchi G, Garcia C, Luciana V, Florencia F, Ruben G, Gelersztein E, Rey G, Sanchez C, Fornasari L, Di Pierro L, Giacomi G, Miguel S, Laura T, Gonzalo C, Ramon C, Glenny J, Koretzky M, Porto A, Tiberio O, Ellenberg A, Saurral R, Igarzabal C, Vilamajo O, Matkovich J, de Lapertosa S, Villagra M, Cuzziol G, de la Cruz M, Pinchetti R, Mierez M, Lopez C, Gorosito V, Gabito A, Kleiban A, Grosembacher L, Adrian P, Paula R, Javier G, Kraft F, Andres F, Krynski F, Nicolas P, Marcelo F, Alfredo F, de la Fuente R, Natalia C, Luquez H, Recuero Y, Becchetti N, Ruiz M, Costantino M, Vazquez G, Guzman C, Pelatia P, Maffei L, Sassone S, Yantorno M, Prado G, Khron B, Maldonado N, Gustavo L, Veronica V, Marino J, Elizabeth A, Alejandra C, Oscar R, Azize G, Gallardo M, Escudero M, Vargas E, Ramos H, Lucero C, Najenson M, Crocci I, Chiesa A, Nardone L, Dominguez S, Zanini A, Manghi F, Grossman M, Giudice G, Romeo A, Piskorz D, Miguel C, Susana D, Noeli U, Rosa S, Martin V, Soledad A, Virginia M, Lorena G, Prado A, Veronica L, Eduardo H, Adolfo P, Florencia W, Rista L, Scolari C, Rojas N, Bertolio V, Zarandon R, Jair S, Orlando C, Sanabria H, Ignacio D, Viviana C, Marina R, Sarjanovich R, Scaro G, Huerta C, Mana M, Gutierrez M, Dain A, Gavicola R, Sessa H, Sacripanti J, Felman R, Vilarino P, Sicer M, Lagrutta M, Sala J, Casabella T, Cecilia H, Carlos B, Vines G, Javier R, Vico M, Lanchiotti P, Martella C, Torres L, Villarino A, Molina M, Martinez J, Farias C, Bertola S, Rojas M, Guzman P, Nisi J, Martinez D, Barrionuevo M, Vita N, Lopez A, Vottero E, Giuliano M, Paron L, Vogel D, Mele P, Imposti H, Dominguez A, Zaidman C, Fernando G, Beck M, Beltrame P, Chemello D, Junior R, Abreu A, Fernandes V, Saboia J, Rodrigues L, Carvalho M, Gurgel M, Gadelha D, Ramos C, Borba V, Golbert M, Pitthan M, Golbert L, Valentini R, Canani L, Gross J, Valenti A, Sartori C, Dutra O, Azevedo E, Azevedo A, Vaz R, Vaz H, da Costa F, da Costa L, Panarotto D, Lain F, Camazzola F, Dellomea B, Rech R, Pizzato P, Nunes C, Jaeger C, Silveira D, Wagner L, Machado L, Rea R, de Bem A, Alves J, Jonasson T, Malucelli F, Betti R, Lerario A, Lisboa H, Bem J, Tres G, Tavares C, Nardi A, Pozzatto M, Backes L, Reolao J, Scariot E, Ziguer E, Baldissera D, Griz L, Antunes D, Victor F, Freire K, Barros A, Costi B, Sa M, Carneiro A, Felicio J, Felicio K, Penha P, Ferreira J, Melo F, Alves A, Souza A, Costa L, Pinheiro D, Turatti L, Augusto G, Leanca C, Santomauro A, Forti A, Sena R, Marinho A, Facanha C, de Souza K, de Souza A, de Queiroz W, Leite S, Vieira S, Gubert L, Olsen A, Piazzetta G, Fuck A, Ferreira M, Fortes J, Brandao T, Alves F, Radice E, dos Santos J, de Almeida R, Franco D, Saporito W, Eliaschewitz F, de Siqueira K, Bona R, Genestreti P, de Castro D, Visconti G, Sampaio C, Palhares F, Konigsfeld H, Alves E, 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Ocicka-Kozakiewicz A, Jurowiecki J, Stasinska T, Karczewicz-Janowska J, Jaruga J, ZytkiewiczJaruga D, Krupinska E, Pupek-Musialik D, Bogdanski P, Szulinska M, Skrypnik D, Skokowska E, Bojarska-Los M, Giermkowska-Samek M, Pirog M, Wojnowski L, Jelinska A, Gradzka M, Danyluk A, Lysek R, Sliwinska T, Podrazka-Szczepaniak A, Barney M, Tomczyk A, Necki M, Malicka J, Dudzinska M, KiszczakBochynska E, Markiewicz A, Galbas K, Paciorkowski A, Mazur S, Mazur M, Chmielowski A, Swiatek A, Sobocka B, Wis J, Jozefowska M, Kaczmarek M, Timler M, Cieplucha Z, Lazuka L, Lazuka N, Wittek A, Spyra J, Jasiel-Wojculewicz H, Stefanski A, Wierucki L, Hanczuk A, Misiura M, Szmygel K, Kolcowa O, Orlowska-Kunikowska E, Rutkowski M, Ignaszewska-Wyrzykowska A, Popenda G, Maciejewska J, Mostowy A, WojteckaGrabka M, Grazyna M, Wieslaw K, Barbara K, Kramarczuk E, Wojciech C, Jaroslaw H, Ewa B, Karas P, Agnieszka S, Hanna C, Justyna S, Piotr K, Wozniak I, Mateusz W, Katarzyna W, Jacek F, Andrzej J, Cymerman K, 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V, Camelia T, Oana P, Monia A, Onaca A, Mircea O, Mot A, Stolea V, Elena N, Barbonta D, Cristian B, Oana S, Popescu A, Madalina M, Coman A, Anca C, Constantinescu S, Mircea C, Diaconu-Sotropa M, Ene D, Pintilei E, Mihai G, Delia R, Toarba I, Simona H, Negru D, Flaminzeanu F, Iulian C, Maria-Cristina C, Doros R, Cleo S, Sorin B, Demian L, Mihai S, Raul B, Ioana A, Nicolau A, Cosmin P, Isabela G, Elena C, Ileana T, Valuyskikh E, Miroshnichenko E, Klementyeva N, Zelman O, Chumakova G, Vigel A, Leonova N, Pergaeva Y, Stefanovskaya O, Pushkareva S, Antoshkina L, Zheleznova N, Iveitsman, Barbarash O, Zvereva T, Zhuravleva E, Zavyrylina I, Usoltceva E, Savostyanova Y, Kupriyanova T, Krivoshapova K, Kondyukova N, Inozemceva A, Argunova Y, Tsyba L, Belenky D, Mariich O, Terekhova A, Tsygankova O, Kuznetsova E, Nagibovich G, Ivchenko Y, Dobronravov V, Dobronravov A, Bush M, Trofimenko I, Vishnevsky A, Zikov V, Kositsyn D, Palzman Z, Spiridonova T, Rodina N, Polozhentsev S, Mamedova L, Panov A, Abesadze I, Alugishvili M, Ivashkin V, Drapkina O, Korneeva O, Zyatenkova E, Glinkina I, Poluboyarinova I, Gurova O, Raykhman A, Vertkin A, Rodykova I, Shamaeva K, Petrovskaya T, Uzueva E, Milovanov Y, Milovanova S, Milovanova L, Markina M, Dobrosmyslov I, Markov V, Afanasiev S, Babich E, Belokopytova N, Demyanov S, Maximov A, Maximov I, Rebrova T, Shtatolkina M, Masin A, Demko A, Chuyko O, Pronina A, Charf G, Akatova E, Urlaeva I, Nikolin O, Khovaeva Y, Ermachkova L, Burdina E, Shvalb P, Suchkov I, Pshennikov A, Gryaznov S, Rymar O, Dolinskaya Y, Bahareva Y, Mustafina S, Sherbakova L, Ovsyannikova A, Bolshakova O, Polunicheva E, Dora S, Agafyina A, Yashina A, Vasilieva I, Yakhontova P, Selivanova S, Kargapoltseva O, Shilina N, Bayramova G, Sorokin I, Astamirova K, Kuchuk P, Koniushenko D, Malykh N, Dvorkin M, Krovelets T, Konovalova K, Seeber M, van Niekerk F, Siebert H, Steenkamp W, Wiid S, Noeth M, Siebert R, Breedt J, Bouwer J, Kapp C, Venter T, Rayner B, Trinder Y, Rheeder P, Delport E, Mathijs S, Soma P, van Zyl D, Strydom M, Marais A, Badat A, Hansa S, Fourie D, Walton T, Engelbrecht J, Jansen J, Roos J, du Toit S, Lehloenya K, van Zyl L, van Zyl F, Naude M, Mookadam M, van der Merwe A, Trokis J, Lombard L, Coetzee K, Ismail S, Bruning H, Latiff G, Yasmin O, Pillay T, Mohamed Z, Dawood S, Stapelberg A, Abrahams P, Jurgens J, van Heerden P, Swart E, Botha C, Meeding J, Hemus A, Oosthuysen W, Visagie G, Fourie N, Hutton P, van der Merwe N, Chelin N, Everton T, Duki M, Ghila N, Joshi M, Hira M, Madueno F, Martinez B, Sebastian N, Mercadal L, Isbert S, Gonzalez I, Asencio J, Figueras M, Rivas M, Garcia H, Fusalba A, Geat D, Cambra G, Sastre J, Castro F, Mas A, Portillo C, Serrano I, Hernandez S, Fajardo F, Juan C, Ferrer J, Peralta F, Padin C, Mauricio D, Madorell B, San Miguel F, Pedrol N, Trescoli C, Montanana C, Gonzalo M, Capellan J, Estrella A, Martinez C, Montesinos I, Loscos A, Coronado J, Perez J, Castillo B, Alonso C, Quesada V, Teruel J, Perez S, Lama M, del Rio E, Zlova T, Ponomarenko K, Karpenko O, Bezuglova S, Mitskevych L, Kizim S, Nevolina I, Katerenchuk V, Liudmyla B, Ivan K, Rudyk I, Olena M, Anna I, Ganna B, Topchii I, Semenovykh P, Yulia Y, Mykhalchyshyn G, Kirienko D, Kobiliak N, Bodnar, Mykhalchyshyn, Pertseva N, Olena G, Tomashkevych H, Korpachev V, Prybyla O, Kovalchuk A, Kushnarova N, Zinych O, Tseluyko V, Andriy Z, Olga R, Mankovskyy B, Zherdova N, Lykhoshapko O, Logoida P, Godlevska O, Olena V, Olga C, Gyrina O, Alifer O, Dozhuk K, Pekhenko V, Gorobets N, Korneichuk A, Makarenko E, Martynyuk L, Martynuyk O, Stanislavchuk M, Larysa P, Natalia S, Botsyurko V, Kostitska I, Dzeman O, Ablitsov Y, Ivaseiko S, Konovart O, Sandurska S, Vendzilovych Y, Samoylov O, Iryna C, Rozhkivska L, Ulyanchenko I, Kateryna V, Orlenko V, Ivaskina K, Tronko M, Tronko K, Pashkovska N, Stankova N, Vynnychenko L, Bolotnikova N, Demokhova N, Reshotko D, Popova A, Dr Bogdana, Tetiana S, Svitlana D, Oksana R, Vlasenko M, Litvinova S, 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Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
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cardiovascular disease ,type 2 diabetes mellitus ,heart failure ,chronic kidney diseases - Abstract
Background: Individuals with type 2 diabetes mellitus are at increased risk for heart failure (HF), particularly those with coexisting atherosclerotic cardiovascular disease and/or kidney disease. Some but not all dipeptidyl peptidase-4 inhibitors have been associated with increased HF risk. We performed secondary analyses of HF and related outcomes with the dipeptidyl peptidase-4 inhibitor linagliptin versus placebo in CARMELINA (The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin), a cardiovascular outcomes trial that enrolled participants with type 2 diabetes mellitus and atherosclerotic cardiovascular disease and/or kidney disease. Methods: Participants in 27 countries with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease were randomized 1:1 to receive once daily oral linagliptin 5 mg or placebo, on top of standard of care. All hospitalization for HF (hHF), cardiovascular outcomes, and deaths were prospectively captured and centrally adjudicated. In prespecified and post hoc analyses of HF and related events, Cox proportional hazards models adjusting for region and baseline history of HF were used. Recurrent hHF events were analyzed using a negative binomial model. In a subset of participants with left ventricular ejection fraction captured within the year before randomization, HF-related outcomes were assessed in subgroups stratified by left ventricular ejection fraction > or 50%. Results: CARMELINA enrolled 6979 participants (mean age, 65.9 years; estimated glomerular filtration rate, mL/min per 1.73m(2); hemoglobin A1c, 8.0%; 62.9% men; diabetes mellitus duration, 14.8 years), including 1873 (26.8%) with a history of HF at baseline. Median follow-up was 2.2 years. Linagliptin versus placebo did not affect the incidence of hHF (209/3494 [6.0%] versus 226/3485 [6.5%], respectively; hazard ratio [HR], 0.90; 95% CI, 0.74-1.08), the composite of cardiovascular death/hHF (HR, 0.94; 95% CI, 0.82-1.08), or risk for recurrent hHF events (326 versus 359 events, respectively; rate ratio, 0.94; 95% CI, 0.75-1.20). There was no heterogeneity of linagliptin effects on hHF by history of HF at baseline, baseline estimated glomerular filtration rate or urine albumin-creatinine ratio, or prerandomization left ventricular ejection fraction. Conclusions: In a large, international cardiovascular outcome trial in participants with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease, linagliptin did not affect the risk of hHF or other selected HF-related outcomes, including among participants with and without a history of HF, across the spectrum of kidney disease, and independent of previous left ventricular ejection fraction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01897532.
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- 2019
50. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk The CARMELINA Randomized Clinical Trial
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Feldman D, Fujino Y, Kitamura H, Toriumi Y, Ishiguro H, Naganuma T, Shu S, Suzuki K, Hirota Y, Hayashi T, Hozawa K, Fukui T, Abe Y, Yamauchi K, Maruyama M, Matsumura S, Kozuma R, Nagai Y, Kihara Y, Maeda H, Nakanishi K, Iitsuka T, Hatori M, Shinozaki Y, Akiyama D, Kawabe M, Takei M, Sato A, Kawai Y, Kitajima K, Ide M, Sato N, Morisaki H, Nakashima K, Takayanagi H, Watanabe H, Iwahashi N, Tsujimoto M, Hibuse K, Hata T, Ueno K, Tatsuma H, Wakida Y, Ito T, Mizuno R, Fujita H, Konishi N, Kanehira T, Watanabe R, Miyaoka H, Okada T, Yamamoto M, Okita S, Murakami H, Todo Y, Umeoka F, Hori K, Shiraishi K, Tada F, Shimizu T, Tamai J, Sasaki C, Okuzima Y, Yasuda M, Iwaita Y, Tanaka K, Rha S, Na J, Cho D, Cho Y, Hwang E, Choi T, Won K, Kim H, Kim S, Oh D, Lee J, Choi H, Chung H, Park H, Suh Y, Kim Y, Kim N, Kim K, An J, Kim J, Park K, Kwak S, Kim M, Hwangbo Y, Lee D, Hong A, Kim L, Oh C, Moon S, Jung C, Jin J, Hyun B, Yang Y, Kong S, Yoon K, Yang H, Hong T, Oh J, Park J, Lee H, Choi J, Ahn J, Han S, Park W, Jo S, Suh S, An W, Park M, Lee S, Kim D, Jin H, Seo J, Chung C, Lim J, Huh J, Park I, Yu S, Sim N, Khan S, Albakari N, Sivaraman J, Manaf K, Maharuddin I, Nagendram S, Ali N, Abdul Latiff N, Othman N, Sarip S, Chew E, Mohamed S, Aziz N, Hui K, Lin L, Velaiutham S, Khir A, Lee L, Manikam S, Chooi K, Chang M, Ooi C, Anthony J, Seganathirajah M, Ng O, Ismail N, Cheah C, Ramanathan G, Mui N, Wen F, Choo T, Bin Ruhani A, Jamaludin S, Abidin S, Nor F, Abu Hassan M, Hanari N, Ahmad N, Suan M, Zainul N, Ali S, Sridhar G, Han C, Chin A, Vin L, Kadir K, Zain A, Hussain N, Pusparajah P, Lozano F, Gomez A, Zaccari E, Vigil A, Preciado C, de Leon M, Parra M, Cervantes A, Aguirre E, Orozco E, Gonzalez S, Elizondo R, Flores E, Guerrero M, Flores F, Sanchez J, Perez F, Rodriguez J, Martinez L, Marquez D, Gutierrez B, Flores M, Real M, Campos P, Garcia P, Rios M, Romero E, Perez Z, Tarabay C, Munoz L, Farias J, Gonzalez J, Palestino N, Sanchez L, Carrillo G, Ordonez N, Pech C, Andrade M, Euan J, Ortegon M, Garcia S, Orozco J, Vazquez H, Herrera R, Perez E, Arango A, Ibarra M, Gonzales L, Esperano J, Quintana L, Salazar I, Ruiz L, Barron C, Ballesteros C, Cervera L, Hercilla E, Gomez H, Mesa J, Herrera P, Rodriguez M, Ochoa R, Mora E, Charles C, Silva R, Mijangos J, Diaz C, Zavala C, Baron P, Bernal A, Martinez F, Tlapale M, Ramirez E, Basila A, Munguia R, Tello M, Martinez M, Mulder H, van der Graaff P, Nawaz A, Keller I, Schoofs M, Smak-Gregoor P, Al-Windy N, Bulut S, de Jong J, Maas A, Schaardenburgh P, Imholz B, Heijster J, Hoogenberg K, Smit C, Kooy A, Huvers F, Landewe-Cleuren S, Kars M, van Moorsel D, Wolffenbuttel B, Lutgens H, Schutte E, Gansevoort R, Idzerda N, Westerink J, Weijmans M, Berg J, van Kleef M, Slob M, Jaspers N, Hovens M, Monajemi H, Kobielusz-Gembala I, Zmuda W, Adamczyk M, Konieczny M, Strzelecka-Sosik A, Nowacka E, Krzyzagorska E, Sekulska M, CzajkowskaKaczmarek E, Kaczmarek B, Opawska K, Dabrowska M, Kus W, Wrzesien-Kus A, Piotrowski G, Hotlos L, Ocicka-Kozakiewicz A, Jurowiecki J, Stasinska T, Karczewicz-Janowska J, Jaruga J, ZytkiewiczJaruga D, Krupinska E, Pupek-Musialik D, Bogdanski P, Szulinska M, Skrypnik D, Skokowska E, Bojarska-Los M, Giermkowska-Samek M, Pirog M, Wojnowski L, Jelinska A, Gradzka M, Danyluk A, Lysek R, Sliwinska T, Podrazka-Szczepaniak A, Barney M, Tomczyk A, Necki M, Malicka J, Dudzinska M, KiszczakBochynska E, Markiewicz A, Galbas K, Paciorkowski A, Mazur S, Mazur M, Chmielowski A, Swiatek A, Sobocka B, Wis J, Jozefowska M, Kaczmarek M, Timler M, Cieplucha Z, Lazuka L, Lazuka N, Wittek A, Spyra J, Jasiel-Wojculewicz H, Stefanski A, Wierucki L, Hanczuk A, Misiura M, Szmygel K, Kolcowa O, Orlowska-Kunikowska E, Rutkowski M, Ignaszewska-Wyrzykowska A, Popenda G, Maciejewska J, Mostowy A, WojteckaGrabka M, Grazyna M, Wieslaw K, Barbara K, Kramarczuk E, Wojciech C, Jaroslaw H, Ewa B, Karas P, Agnieszka S, Hanna C, Justyna S, Piotr K, Wozniak I, Mateusz W, Katarzyna W, Jacek F, Andrzej J, Cymerman K, Gmytrasiewicz M, Zambrzycki J, Krysiak-Kowaluk H, Klodawska K, Klszczewski Z, Zieleniewski J, Opadczuk P, Urbanska K, Faran-Grabowska K, Szczepanik T, Siegel A, Kleczek A, Kincel K, Nowak D, Slowik-Gomulka L, Watemborska-Matuszyk G, Lampart J, Strozik-Krecichwost A, Dziewit T, Broncel M, Wojcik-Odyniec J, Jakubczyk E, Wierzbicka K, Witowicz A, Jedrych B, Korczyk P, Socik-Pojawa M, Monteiro P, Monteiro S, Mendes P, Soares F, Mendes S, Leite L, Vicente J, Santos M, Ferreira A, Alves P, Rosario F, Garrao A, Duarte L, Rogado C, Duarte R, Laginha T, Matos P, Raposo J, Mariz J, Teixeira J, Capela C, Leitao A, Cardiga R, Alface M, Augusto S, Basto L, Cunha A, Rei D, Dantas J, Verdasca I, Andrade L, Silva A, Suarez M, Dias V, Silva J, Pereira N, Goncalves M, Goncalves A, Silveira A, Sampaio A, Dias A, Diogo M, Vilaca C, Cif A, Calin T, Elena S, Crisan C, Adina S, Ramona S, Anghel V, Simona C, Turcu L, Mihaela V, Cosma D, Cristina H, Marius-Calin H, Negrisanu G, Andreea-Andrada M, Maria-Mihaela V, Camelia T, Oana P, Monia A, Onaca A, Mircea O, Mot A, Stolea V, Elena N, Barbonta D, Cristian B, Oana S, Popescu A, Madalina M, Coman A, Anca C, Constantinescu S, Mircea C, Diaconu-Sotropa M, Ene D, Pintilei E, Mihai G, Delia R, Toarba I, Simona H, Negru D, Flaminzeanu F, Iulian C, Maria-Cristina C, Doros R, Cleo S, Sorin B, Demian L, Mihai S, Raul B, Ioana A, Nicolau A, Cosmin P, Isabela G, Elena C, Ileana T, Valuyskikh E, Miroshnichenko E, Klementyeva N, Zelman O, Chumakova G, Vigel A, Leonova N, Pergaeva Y, Stefanovskaya O, Pushkareva S, Antoshkina L, Zheleznova N, Iveitsman, Barbarash O, Zvereva T, Zhuravleva E, Zavyrylina I, Usoltceva E, Savostyanova Y, Kupriyanova T, Krivoshapova K, Kondyukova N, Inozemceva A, Argunova Y, Tsyba L, Belenky D, Mariich O, Terekhova A, Tsygankova O, Kuznetsova E, Nagibovich G, Ivchenko Y, Dobronravov V, Dobronravov A, Bush M, Trofimenko I, Vishnevsky A, Zikov V, Kositsyn D, Palzman Z, Spiridonova T, Rodina N, Polozhentsev S, Mamedova L, Panov A, Abesadze I, Alugishvili M, Ivashkin V, Drapkina O, Korneeva O, Zyatenkova E, Glinkina I, Poluboyarinova I, Gurova O, Raykhman A, Vertkin A, Rodykova I, Shamaeva K, Petrovskaya T, Uzueva E, Milovanov Y, Milovanova S, Milovanova L, Markina M, Dobrosmyslov I, Markov V, Afanasiev S, Babich E, Belokopytova N, Demyanov S, Maximov A, Maximov I, Rebrova T, Shtatolkina M, Masin A, Demko A, Chuyko O, Pronina A, Charf G, Akatova E, Urlaeva I, Nikolin O, Khovaeva Y, Ermachkova L, Burdina E, Shvalb P, Suchkov I, Pshennikov A, Gryaznov S, Rymar O, Dolinskaya Y, Bahareva Y, Mustafina S, Sherbakova L, Ovsyannikova A, Bolshakova O, Polunicheva E, Dora S, Agafyina A, Yashina A, Vasilieva I, Yakhontova P, Selivanova S, Kargapoltseva O, Shilina N, Bayramova G, Sorokin I, Astamirova K, Kuchuk P, Koniushenko D, Malykh N, Dvorkin M, Krovelets T, Konovalova K, Seeber M, van Niekerk F, Siebert H, Steenkamp W, Wiid S, Noeth M, Siebert R, Breedt J, Bouwer J, Kapp C, Venter T, Rayner B, Trinder Y, Rheeder P, Delport E, Mathijs S, Soma P, van Zyl D, Strydom M, Marais A, Badat A, Hansa S, Fourie D, Walton T, Engelbrecht J, Jansen J, Roos J, du Toit S, Lehloenya K, van Zyl L, van Zyl F, Naude M, Mookadam M, van der Merwe A, Trokis J, Lombard L, Coetzee K, Ismail S, Bruning H, Latiff G, Yasmin O, Pillay T, Mohamed Z, Dawood S, Stapelberg A, Abrahams P, Jurgens J, van Heerden P, Swart E, Botha C, Meeding J, Hemus A, Oosthuysen W, Visagie G, Fourie N, Hutton P, van der Merwe N, Chelin N, Everton T, Duki M, Ghila N, Joshi M, Hira M, Madueno F, Martinez B, Sebastian N, Mercadal L, Isbert S, Gonzalez I, Asencio J, Figueras M, Rivas M, Garcia H, Fusalba A, Geat D, Cambra G, Sastre J, Castro F, Mas A, Portillo C, Serrano I, Hernandez S, Fajardo F, Juan C, Ferrer J, Peralta F, Padin C, Mauricio D, Madorell B, San Miguel F, Pedrol N, Trescoli C, Montanana C, Gonzalo M, Capellan J, Estrella A, Martinez C, Montesinos I, Loscos A, Coronado J, Perez J, Castillo B, Alonso C, Quesada V, Teruel J, Perez S, Lama M, del Rio E, Zlova T, Ponomarenko K, Karpenko O, Bezuglova S, Mitskevych L, Kizim S, Nevolina I, Katerenchuk V, Liudmyla B, Ivan K, Rudyk I, Olena M, Anna I, Ganna B, Topchii I, Semenovykh P, Yulia Y, Mykhalchyshyn G, Kirienko D, Kobiliak N, Bodnar, Mykhalchyshyn, Pertseva N, Olena G, Tomashkevych H, Korpachev V, Prybyla O, Kovalchuk A, Kushnarova N, Zinych O, Tseluyko V, Andriy Z, Olga R, Mankovskyy B, Zherdova N, Lykhoshapko O, Logoida P, Godlevska O, Olena V, Olga C, Gyrina O, Alifer O, Dozhuk K, Pekhenko V, Gorobets N, Korneichuk A, Makarenko E, Martynyuk L, Martynuyk O, Stanislavchuk M, Larysa P, Natalia S, Botsyurko V, Kostitska I, Dzeman O, Ablitsov Y, Ivaseiko S, Konovart O, Sandurska S, Vendzilovych Y, Samoylov O, Iryna C, Rozhkivska L, Ulyanchenko I, Kateryna V, Orlenko V, Ivaskina K, Tronko M, Tronko K, Pashkovska N, Stankova N, Vynnychenko L, Bolotnikova N, Demokhova N, Reshotko D, Popova A, Dr Bogdana, Tetiana S, Svitlana D, Oksana R, Vlasenko M, Litvinova S, Semenyuk I, Fishchuk O, Mostovoy Y, Tkachenko T, Ovcharuk M, Rasputina L, Vakaliuk I, Tymochko N, Drapchak I, Petrovska L, Lai W, Yen H, Voon W, Lin T, Cheng K, Chiu C, Chu C, Hsu P, Chiang C, Li Y, Kuo C, Lin S, Chao T, Yu W, Sung S, Wang K, Lu T, Shih K, Wu C, Chiang F, Hwang J, Tsai C, Juang J, Jeng J, Tang S, Lai C, Cheng C, Hsieh I, Hsieh M, Chen C, Lee C, Pai P, Ko P, Wang T, Chen T, Wu H, Chang S, Chen K, Hsieh L, Chou C, Jiang J, Lee M, Huang J, Chen J, Chiu K, Tsai L, Chen P, Saxena M, Collier D, Vaidya B, Harman S, Ramell M, Davies M, Chatterjee S, Meakin L, Quinn M, Bain S, Mallipedhi A, Min T, Bashir J, Blagden M, Ali J, McCrimmon R, Brennan G, Malcolm E, McDonald D, Pearson E, Illsley G, Darzy K, Winocour P, Hanif W, Cockwell P, Charlton M, Thekkepat S, Howat I, Devers M, Patrick J, Wyatt N, Smith C, Singh B, Nicholas J, Gillani S, Green F, Bell E, Boyle J, MacKin S, Livingstone R, Arif A, Syed M, Hammoud J, Sparks J, Anderson M, Tumey R, Condit J, Reddy M, Abalos-Galito M, Rebecca J, Barker T, Seaton B, Campbell E, Kompanik H, Jayson L, Huffman C, Bialow M, McDonnell G, McCaffrey J, Manis C, DeLuca E, Levins J, Bartlett M, Anorga K, Franco M, Gentry P, Hodge D, Pohil R, Rschultz, Leggett R, Blair L, Gisler J, Niegos F, Osburn M, Parma K, Schendel S, Stines L, Winnie M, Wu P, Canales J, Yu J, Cornett G, Beavins J, Hyde D, Zapinski D, Johnson T, Levinson D, Ahmed A, Kenny B, Kuehl A, Bates C, Jantzi C, Ananthula P, Shafer J, Louthan J, Bays A, Stapleton A, Staton P, Strum D, Taylor P, Smith A, Rapp R, Bao S, Randolph C, MacGillivray B, Schuster R, Harden T, Barnella C, Dunnam T, Whiles R, Bolick C, Brockmyre A, Plucker S, Marshall C, Poteet C, Morin D, Tavel E, Averill N, McFann A, Purcell D, Dixon T, Corey E, Goss J, Drescher R, Irfan M, Naeem M, Egelhof R, Mehta P, Koehler T, Walia J, Fernandez J, Bedel G, Preet R, Bhuchar S, Ahmed F, Onyema D, Benchabbat A, Kohanbash L, Miller P, Lalinde M, Carrithers E, Patterson R, Raube-Miceli A, Martinez A, Harris B, Levy R, Siev E, Berlin H, DiMattia M, Sugimoto D, Dugas J, Benson M, Stegemoller R, Schmoll M, Kinnaman S, O'Connor T, Powel T, Rudolph L, Lewiecki M, Best E, Chavez J, Garcia M, Cohen R, Colman D, Ocampo M, Heaney L, Rappley G, Quezada I, Santos V, Nikfarjam A, Reyes M, Rodriguez R, Josephs L, Hernandez R, Flores P, Espinoza L, Mejia W, Pedraza Z, Castaneda R, Laguerre J, Cook R, Patel R, Werner H, Blank R, Small S, Andersen J, Holmes D, Farmer M, Wiener V, Pharr W, Bray B, Beekman J, Anderson A, Andrawis N, Gabra N, Moche T, Marty S, Galvez O, Reyes R, Garcia R, Lerma G, Pliquin B, Mayfield R, Durham N, Phillips R, Baran A, Kondo N, Dempsey S, Kufs W, Laddis T, Zimmer K, Van Depol M, Dweck L, Kestler M, Werner N, Ashraf M, Quick A, Schallert G, Sligh T, Trueba P, Batista J, Martinez T, Moya J, Amarales V, Santos E, Torres P, Diaz T, Diaz J, Hodish I, Else T, Buras E, Moratis A, Valika S, Rahman A, Malalis W, Box E, Box P, Kerwood B, Nagaeva J, Metz C, Hinnant J, Griswell D, 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- Abstract
IMPORTANCE Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease. OBJECTIVE To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A(1c) of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] > 200mg/g), and high renal risk (reduced eGFR and micro-or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. INTERVENTIONS Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. MAIN OUTCOMES AND MEASURES Primary outcomewas time to first occurrence of the composite of CV death, nonfatalmyocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. RESULTS Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73m2; 80.1% with UACR > 30mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI,-0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P
- Published
- 2019
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