Observation of magnetic islands in tokamak plasmas during the suppression of edge-localized modes

In tokamaks, a leading platform for fusion energy, periodic filamentary plasma eruptions known as edge-localized modes occur in plasmas with high-energy confinement and steep pressure profiles at the plasma edge. These edge-localized modes could damage the tokamak wall but can be suppressed using small three-dimensional magnetic perturbations. Here we demonstrate that these magnetic perturbations can change the magnetic topology just inside the steep gradient region of the plasma edge. We identify signatures of a magnetic island, and their observation is linked to the suppression of edge-localized modes. We compare high-resolution measurements of perturbed magnetic surfaces with predictions from ideal magnetohydrodynamic theory where the magnetic topology is preserved. Although ideal magnetohydrodynamics adequately describes the measurements in plasmas exhibiting edge-localized modes, it proves insufficient for plasmas where these modes are suppressed. Nonlinear resistive magnetohydrodynamic modelling supports this observation. Our study experimentally confirms the predicted role of magnetic islands in inhibiting the occurrence of edge-localized modes. This will be beneficial for physics-based predictions in future fusion devices to control these modes.This material is based upon work supported by the US Department of Energy under award DE-SC0021968. This work has been carried out within the framework of the EUROfusion Consortium, funded by the European Union via the Euratom Research and Training Programme (grant agreement no. 101052200-EUROfusion).Peer ReviewedArticle signat per 437 autors: Max Planck Institute for Plasma Physics, Garching, Germany: Matthias Willensdorfer, Verena Mitterauer, Matthias Hoelzl, Wolfgang Suttrop, Mike Dunne, Rainer Fischer, Jonas Puchmayr, Oleg Samoylov, Daniel Wendler, C. Angioni, N. Arden, V. Artigues, M. Astrain, M. Balden, V. Bandaru, A. Banon Navarro, M. Bauer, A. Bergmann, M. Bergmann, M. Bernert, R. Bilato, G. Birkenmeier, V. Bobkov, A. Bock, L. Bock, T. Body, N. Bonanomi, B. Böswirth, A. Bottino, D. Brida, A. Buhler, A. Burckhart, P. Cano Megías, D. Carlton, A. Castillo Castillo, A. Chankin, G. Conway, D. Coster, P. David, P. de Marné, A. Di Siena, M. Dibon, M. Dunne, R. Dux, S. Elgeti, E. Fable, M. Faitsch, D. Fajardo Jimenez, U. Fantz, H. Faugel, R. Fischer, M. Fröschle, J. C. Fuchs, H. Fünfgelder, L. Giannone, O. Girka, T. Gleiter, S. Glöggler, J. C. Gonzalez, T. Görler, A. Gräter, G. Grenfell, H. Greuner, M. Griener, O. Grover, A. Gude, S. Günter, T. Happel, N. den Harder, T. Hayward-Schneider, B. Heinemann, P. Heinrich, A. Herrmann, J. Hobirk, M. Hölzl, C. Hopf, T. Höschen, K. Hunger, V. Igochine, J. Illerhaus, W. Jacob, N. Jaksic, F. Janky, F. Jenko, A. Kallenbach, J. Kalis, A. Kappatou, C.-P. Käsemann, M. Kircher, F. Klossek, M. Koleva, M. Krause, A. Kreuzeder, K. Krieger, O. Kudlacek, B. Kurzan, K. Lackner, P. T. Lang, P. Lauber, E. Lerche, O. Linder, Z. Lu, T. Luda di Cortemiglia, T. Lunt, T. Maceina, A. Magnanimo, H. Maier, O. Maj, A. Manhard, M. Maraschek, F. Matos, M. Mayer, R. McDermott, R. Merkel, M. Michelini, P. Molina Cabrera, M. Muraca, R. Neu, T. Nishizawa, I. Novikau, R. Ochoukov, O. Pan, G. Papp, G. Pautasso, M. Peglau, U. Plank, B. Plöckl, E. Poli, J. Puchmayr, T. Pütterich, G. Raupp, M. Reich, M. Reisner, B. Rettino, T. Ribeiro, R. Riedl, J. Riesch, V. Rohde, M. Rott, F. Ryter, O. Samoylov, G. Schall, A. Schlüter, K. Schmid, P. A. Schneider, M. Schubert, C. Schuster, T. Schwarz-Selinger, J. Schweinzer, F. Sciortino, O. Seibold-Benjak, M. Siccinio, B. Sieglin, A. Sigalov, D. Silvagni, M. Spacek, A. Stegmeir, D. Stieglitz, J. Stober, U. Stroth, E. Strumberger, W. Suttrop, B. Tál, G. Tardini, M. Teschke, W. Tierens, D. Told, W. Treutterer, P. Ulbl, G. Urbanczyk, M. Usoltseva, F. Vannini, T. Vierle, G. Vogel, U. von Toussaint, D. Wagner, X. Wang, M. Weiland, D. Wendler, M. Willensdorfer, B. Wiringer, M. Wischmeier, E. Wolfrum, Q. Yu, I. Zammuto, T. Zehetbauer, W. Zholobenko, M. Zilker, B. Zimmermann, A. Zito & H. Zohm // Oak Ridge National Laboratory, Oak Ridge, TN, USA: Mark Cianciosa // Columbia University, New York, NY, USA: Nils Leuthold, N. Leuthold & C. Paz-Soldan // ITER Organization, Saint-Paul-lèz-Durance, France: Guillermo Suárez López, A. Encheva, S. Jachmich, M. Lehnen, G. Suarez Lopez & S. Vanmulders // Physics Department, TUM School of Natural Sciences, Technical University of Munich, Garching, Germany: Daniel Wendler, S. Glöggler, F. Hitzler, U. Stroth & D. Wendler // Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal: D. Aguiam, J. Bernardo, P. Carvalho, R. Coelho, A. Figueredo, L. Gil, L. Guimarais, D. Hachmeister, F. Nabais, V. Plyusnin, J. Santos, E. Seliunin, A. Silva, C. Silva, P. Varela & J. Vicente // ENEA, IFP-CNR, Milan, Italy: E. Alessi, G. Croci, S. Garavaglia, G. Granucci, A. Mancini, P. Mantica, S. Nowak, D. Ricci, C. Sozzi & M. Tardocchi // Department of Applied Physics, Aalto University, Espoo, Finland: O. Asunta, M. Groth, J. Karhunen, T. Kurki-Suonio, A. Lahtinen, I. Paradela Perez, A. Salmi, S. Sipilä & A. Snicker // Léonard de Vinci Pôle Universitaire Research Center, Paris, France: A. Biancalani // MIT Plasma Science and Fusion Center, Cambridge, MA, USA: R. Bielajew, A. Hubbard, P. Rodriguez-Fernandez, B. Vanovac, A. E. White & C. Yoo // Eindhoven University of Technology, Eindhoven, the Netherlands: T. Blanken, H. van den Brand, M. de Baar, M. Kantor, E. Maljaars, G. Ronchi & J. Scholte // Consorzio RFX, Padova, Italy: T. Bolzonella, C. Cazzaniga, R. Delogu, M. Gobbin, L. Marrelli, P. Martin, C. Piron, G. Spizzo, M. Spolaore, D. Terranova, G. Trevisan, M. Valisa & N. Vianello // Princeton Plasma Physics Laboratory, Princeton, NJ, USA: A. Bortolon, F. Laggner, R. Maingi & R. Nazikian // CEA/IRFM, Saint-Paul-lèz-Durance, France: C. Bottereau, F. Clairet, L. Colas, A. Gallo & E. Joffrin // Forschungszentrum Jülich, Jülich, Germany: M. Brenzke, S. Brezinsek, J. W. Coenen, P. Denner, Y. Gao, A. Huber, A. Krämer-Flecken, L. Li, D. Reiser & D. Reiter // Institut Jean Lamour, Université de Lorraine, Nancy, France: F. Brochard, S. Heuraux & A. Houben // CCFE, Culham Science Centre, Abingdon, UK: J. Buchanan, M. Carr, C. Challis, C. Ham, J. Harrison, S. Henderson, A. Kirk, J. Mailloux, M.-L. Mayoral, H. Meyer, D. A. Ryan, S. Saarelma, S. Sharapov, J. Simpson, M. Valovic & I. Voitsekhovitch // Aix-Marseille University, CNRS, Marseille, France: Y. Camenen // Department of Electrical and Electronic Engineering, University of Cagliari, Cagliari, Italy: B. Cannas & G. Sias // ENEA, Centro Ricerche Frascati, Frascati, Italy: C. Castaldo, C. Cianfarani, B. Esposito, E. Giovannozzi & G. Rocchi // ENEA, University of Milano-Bicocca, Milano, Italy: M. Cavedon, A. Dal Molin, G. Gorini & M. Nocente // Institute of Plasma Physics and Laser Microfusion, Warsaw, Poland: A. Chomiczewska, K. Galazka, I. Ivanova-Stanik & R. Zagorski // Ecole Polytechnique Fédérale de Lausanne, Swiss Plasma Center, Lausanne, Switzerland: S. Coda, B. P. Duval, F. Felici, T. Goodman, M. Kong, B. Labit, A. Merle, A. Pau, L. Porte, O. Sauter, A. Shalpegin, U. Sheikh & C. Sommariva // ÖAW, IAP, University of Innsbruck, Innsbruck, Austria: S. Costea, C. Ionita-Schrittwieser, A. Kendl & R. Schrittwieser // University of Wisconsin, Madison, WI, USA: T. Cote, B. Geiger & O. Schmitz // CFS, Fort Devens, MA, USA: A. J. Creely & T. Eich // Universidad de Sevilla, Sevilla, Spain: D. J. Cruz Zabala, J. J. Dominguez Palacios Durán, J. Galdon-Quiroga, M. Garcia Muñoz, J. Gonzalez Martin, A. Jansen van Vuuren, P. Oyola, J. F. Rivero Rodriguez, L. Sanchis Sanchez & E. Viezzer // Centre for Energy Research, Budapest, Hungary: G. Cseh, D. Dunai, G. Kocsis, G. Pokol, D. Réfy, T. Szepesi & S. Zoletnik // York Plasma Institute, University of York, York, UK: I. Cziegler, L. Horvath & B. Lipschultz // ENEA Consorzio CREATE, Naples, Italy: O. D’Arcangelo // Karlsruhe Institut für Technologie, Karlsruhe, Germany: C. Day, V. Hauer & S. Varoutis // Institute of Plasma Physics, National Science Center Kharkov Institute of Physics and Technology, Krakov, Ukraine: M. Dreval // Institute of Plasma Physics of the CAS, Praha, Czech Republic: M. Farnik, O. Ficker, F. Jaulmes & M. Komm // Max-Planck-Institut für Plasmaphysik, Greifswald, Germany: O. Ford, G. Fuchert, D. Gradic, K. Höfler, D. Kulla, F. Reimold & R. Wolf // KTH Royal Institute of Technology, Stockholm, Sweden: L. Frassinetti, P. Petersson, S. Ratynskaia, M. Rubel & E. Thorén // Barcelona Supercomputing Center, Barcelona, Spain: S. Futatani, D. Gallart Escolà & M. Mantsinen // Department of Physics, Durham University, Durham, UK: S. Gibson // VTT Technical Research Centre of Finland, Espoo, Finland: A. H. Hakola, J. Likonen & T. Tala // ÖAW, IAP, Vienna University of Technology, Vienna, Austria: G. Harrer, W. Kernbichler, P. Lainer, M. Markl & L. Radovanovic // General Atomics, San Diego, CA, USA: T. Hellsten, Y. Liu & M. van Zeeland // Laboratoire de Physique des Plasmas, Ecole Polytechnique, Palaiseau, France: P. Hennequin // ÖAW, Graz University of Technology, Graz, Austria: E. Heyn & S. Kasilov // Department of Physics, Technical University of Denmark, Lyngby, Denmark: J. H. Holm, T. Jensen, S. Kjer Hansen, J. Madsen, V. Naulin, R. D. Nem, A. H. Nielsen, S. K. Nielsen, J. Olsen, J. Rasmussen, M. Salewski, M. Stejner & T. Verdier // Ioffe Institute, St. Petersburg, Russian Federation: M. Iliasova, E. Khilkevitch & A. Shevelev // Department of Physics, Chalmers University of Technology, Gothenburg, Sweden: K. Insulander Björk // ERM/KMS, Brussels, Belgium: Y. Kazakov, A. Lyssoivan, V. Maquet, M. Tripský & G. Verdoolaege // Ghent University, Ghent, Belgium: V. Klevarova, A. Shabbir & G. Verdoolaege // Electrical and Computer Engineering, University of California, Davis, CA, USA: N. C. Luhmann // ICREA, Barcelona, Spain: M. Mantsinen // Universität Greifswald, Greifswald, Germany: P. Manz // ISC-CNR, Politecnico di Torino, Turin, Italy: C. Marchetto & D. Milanesio // School of Physics, University College Cork, Cork, Ireland: P. J. McCarthy // Technische Universität München, Garching, Germany: R. Neu // Department of Industrial Engineering, University of Rome, Rome, Italy: E. Peluso // IGVP Universität Stuttgart, Stuttgart, Germany: B. Plaum & M. Ramisch // Budapest University of Technology and Economics, Budapest, Hungary: G. Pokol // Laboratorio Nacional de Fusión, CIEMAT, Madrid, Spain: G. Ratta & E. Solano // Universitá degli Studi della Tuscia, DEIM Department, Viterbo, Italy: A. Redl // Chinese Academy of Sciences, Hefei, China: Q. Yang & W. Zhang // Consortia the ASDEX Upgrade Team: D. Aguiam, E. Alessi, C. Angioni, N. Arden, V. Artigues, M. Astrain, O. Asunta, M. Balden, V. Bandaru, A. Banon Navarro, M. Bauer, A. Bergmann, M. Bergmann, J. Bernardo, M. Bernert, A. Biancalani, R. Bielajew, R. Bilato, G. Birkenmeier, T. Blanken, V. Bobkov, A. Bock, L. Bock, T. Body, T. Bolzonella, N. Bonanomi, A. Bortolon, B. Böswirth, C. Bottereau, A. Bottino, H. van den Brand, M. Brenzke, S. Brezinsek, D. Brida, F. Brochard, J. Buchanan, A. Buhler, A. Burckhart, Y. Camenen, B. Cannas, P. Cano Megías, D. Carlton, M. Carr, P. Carvalho, C. Castaldo, A. Castillo Castillo, M. Cavedon, C. Cazzaniga, C. Challis, A. Chankin, A. Chomiczewska, C. Cianfarani, F. Clairet, S. Coda, R. Coelho, J. W. Coenen, L. Colas, G. Conway, S. Costea, D. Coster, T. Cote, A. J. Creely, G. Croci, D. J. Cruz Zabala, G. Cseh, I. Cziegler, O. D’Arcangelo, A. Dal Molin, P. David, C. Day, M. de Baar, P. de Marné, R. Delogu, P. Denner, A. Di Siena, M. Dibon, J. J. Dominguez Palacios Durán, D. Dunai, M. Dreval, M. Dunne, B. P. Duval, R. Dux, T. Eich, S. Elgeti, A. Encheva, B. Esposito, E. Fable, M. Faitsch, D. Fajardo Jimenez, U. Fantz, M. Farnik, H. Faugel, F. Felici, O. Ficker, A. Figueredo, R. Fischer, O. Ford, L. Frassinetti, M. Fröschle, G. Fuchert, J. C. Fuchs, H. Fünfgelder, S. Futatani, K. Galazka, J. Galdon-Quiroga, D. Gallart Escolà, A. Gallo, Y. Gao, S. Garavaglia, M. Garcia Muñoz, B. Geiger, L. Giannone, S. Gibson, L. Gil, E. Giovannozzi, O. Girka, T. Gleiter, S. Glöggler, M. Gobbin, J. C. Gonzalez, J. Gonzalez Martin, T. Goodman, G. Gorini, T. Görler, D. Gradic, G. Granucci, A. Gräter, G. Grenfell, H. Greuner, M. Griener, M. Groth, O. Grover, A. Gude, L. Guimarais, S. Günter, D. Hachmeister, A. H. Hakola, C. Ham, T. Happel, N. den Harder, G. Harrer, J. Harrison, V. Hauer, T. Hayward-Schneider, B. Heinemann, P. Heinrich, T. Hellsten, S. Henderson, P. Hennequin, S. Heuraux, A. Herrmann, E. Heyn, F. Hitzler, J. Hobirk, K. Höfler, J. H. Holm, M. Hölzl, C. Hopf, L. Horvath, T. Höschen, A. Houben, A. Hubbard, A. Huber, K. Hunger, V. Igochine, M. Iliasova, J. Illerhaus, K. Insulander Björk, C. Ionita-Schrittwieser, I. Ivanova-Stanik, S. Jachmich, W. Jacob, N. Jaksic, F. Janky, A. Jansen van Vuuren, F. Jaulmes, F. Jenko, T. Jensen, E. Joffrin, A. Kallenbach, J. Kalis, M. Kantor, A. Kappatou, J. Karhunen, C.-P. Käsemann, S. Kasilov, Y. Kazakov, A. Kendl, W. Kernbichler, E. Khilkevitch, M. Kircher, A. Kirk, S. Kjer Hansen, V. Klevarova, F. Klossek, G. Kocsis, M. Koleva, M. Komm, M. Kong, A. Krämer-Flecken, M. Krause, A. Kreuzeder, K. Krieger, O. Kudlacek, D. Kulla, T. Kurki-Suonio, B. Kurzan, B. Labit, K. Lackner, F. Laggner, A. Lahtinen, P. Lainer, P. T. Lang, P. Lauber, M. Lehnen, E. Lerche, N. Leuthold, L. Li, J. Likonen, O. Linder, B. Lipschultz, Y. Liu, Z. Lu, T. Luda di Cortemiglia, N. C. Luhmann, T. Lunt, A. Lyssoivan, T. Maceina, J. Madsen, A. Magnanimo, H. Maier, J. Mailloux, R. Maingi, O. Maj, E. Maljaars, V. Maquet, A. Mancini, A. Manhard, P. Mantica, M. Mantsinen, P. Manz, M. Maraschek, C. Marchetto, M. Markl, L. Marrelli, P. Martin, F. Matos, M. Mayer, M.-L. Mayoral, P. J. McCarthy, R. McDermott, R. Merkel, A. Merle, H. Meyer, M. Michelini, D. Milanesio, P. Molina Cabrera, M. Muraca, F. Nabais, V. Naulin, R. Nazikian, R. D. Nem, R. Neu, A. H. Nielsen, S. K. Nielsen, T. Nishizawa, M. Nocente, I. Novikau, S. Nowak, R. Ochoukov, J. Olsen, P. Oyola, O. Pan, G. Papp, I. Paradela Perez, A. Pau, G. Pautasso, C. Paz-Soldan, M. Peglau, E. Peluso, P. Petersson, C. Piron, U. Plank, B. Plaum, B. Plöckl, V. Plyusnin, G. Pokol, E. Poli, L. Porte, J. Puchmayr, T. Pütterich, L. Radovanovic, M. Ramisch, J. Rasmussen, G. Ratta, S. Ratynskaia, G. Raupp, A. Redl, D. Réfy, M. Reich, F. Reimold, D. Reiser, M. Reisner, D. Reiter, B. Rettino, T. Ribeiro, D. Ricci, R. Riedl, J. Riesch, J. F. Rivero Rodriguez, G. Rocchi, P. Rodriguez-Fernandez, V. Rohde, G. Ronchi, M. Rott, M. Rubel, D. A. Ryan, F. Ryter, S. Saarelma, M. Salewski, A. Salmi, O. Samoylov, L. Sanchis Sanchez, J. Santos, O. Sauter, G. Schall, A. Schlüter, J. Scholte, K. Schmid, O. Schmitz, P. A. Schneider, R. Schrittwieser, M. Schubert, C. Schuster, T. Schwarz-Selinger, J. Schweinzer, F. Sciortino, O. Seibold-Benjak, E. Seliunin, A. Shabbir, A. Shalpegin, S. Sharapov, U. Sheikh, A. Shevelev, G. Sias, M. Siccinio, B. Sieglin, A. Sigalov, A. Silva, C. Silva, D. Silvagni, J. Simpson, S. Sipilä, A. Snicker, E. Solano, C. Sommariva, C. Sozzi, M. Spacek, G. Spizzo, M. Spolaore, A. Stegmeir, M. Stejner, D. Stieglitz, J. Stober, U. Stroth, E. Strumberger, G. Suarez Lopez, W. Suttrop, T. Szepesi, B. Tál, T. Tala, G. Tardini, M. Tardocchi, D. Terranova, M. Teschke, E. Thorén, W. Tierens, D. Told, W. Treutterer, G. Trevisan, M. Tripský, P. Ulbl, G. Urbanczyk, M. Usoltseva, M. Valisa, M. Valovic, M. van Zeeland, S. Vanmulders, F. Vannini, B. Vanovac, P. Varela, S. Varoutis, T. Verdier, G. Verdoolaege, N. Vianello, J. Vicente, T. Vierle, E. Viezzer, G. Vogel, I. Voitsekhovitch, U. von Toussaint, D. Wagner, X. Wang, M. Weiland, D. Wendler, A. E. White, M. Willensdorfer, B. Wiringer, M. Wischmeier, R. Wolf, E. Wolfrum, Q. Yang, C. Yoo, Q. Yu, R. Zagorski, I. Zammuto, T. Zehetbauer, W. Zhang, W. Zholobenko, M. Zilker, B. Zimmermann, A. Zito, H. Zohm & S. ZoletnikPostprint (published version

Genome-wide association study for frozen-thawed sperm motility in stallions across various horse breeds

Objective: The semen quality of stallions including sperm motility is an important target of selection as it has a high level of individual variability. However, effects of the molecular architecture of the genome on the mechanisms of sperm formation and their preservation after thawing have been poorly investigated. Here, we conducted a genome-wide association study (GWAS) for the sperm motility of cryopreserved semen in stallions of various breeds. Methods: Semen samples were collected from the stallions of 23 horse breeds. The following semen characteristics were examined: progressive motility (PM), progressive motility after freezing (FPM), and the difference between PM and FPM. The respective DNA samples from these stallions were genotyped using Axiom™ Equine Genotyping Array. Results: We performed a GWAS search for single nucleotide polymorphism (SNP) markers and potential genes related to motility properties of frozen-thawed semen in the stallions of various breeds. As a result of the GWAS analysis, two SNP markers, rs1141327473 and rs1149048772, were identified that were associated with preservation of the frozen-thawed stallion sperm motility, the relevant putative candidate genes being NME8, OR2AP1 and OR6C4. Potential implications of effects of these genes on sperm motility are herein discussed. Conclusion: The GWAS results enabled us to localize novel SNPs and candidate genes for sperm motility in stallions. Implications of the study for horse breeding and genetics are a better understanding of genomic regions and candidate genes underlying stallion sperm quality, and improvement in horse reproduction and breeding techniques. The identified markers and genes for sperm cryotolerance and the respective genomic regions are promising candidates for further studying the biological processes in the formation and function of the stallion reproductive system

Phenological shifts of abiotic events, producers and consumers across a continent

Ongoing climate change can shift organism phenology in ways that vary depending on species, habitats and climate factors studied. To probe for large-scale patterns in associated phenological change, we use 70,709 observations from six decades of systematic monitoring across the former Union of Soviet Socialist Republics. Among 110 phenological events related to plants, birds, insects, amphibians and fungi, we find a mosaic of change, defying simple predictions of earlier springs, later autumns and stronger changes at higher latitudes and elevations. Site mean temperature emerged as a strong predictor of local phenology, but the magnitude and direction of change varied with trophic level and the relative timing of an event. Beyond temperature-associated variation, we uncover high variation among both sites and years, with some sites being characterized by disproportionately long seasons and others by short ones. Our findings emphasize concerns regarding ecosystem integrity and highlight the difficulty of predicting climate change outcomes. The authors use systematic monitoring across the former USSR to investigate phenological changes across taxa. The long-term mean temperature of a site emerged as a strong predictor of phenological change, with further imprints of trophic level, event timing, site, year and biotic interactions.Peer reviewe

Chronicles of nature calendar, a long-term and large-scale multitaxon database on phenology

We present an extensive, large-scale, long-term and multitaxon database on phenological and climatic variation, involving 506,186 observation dates acquired in 471 localities in Russian Federation, Ukraine, Uzbekistan, Belarus and Kyrgyzstan. The data cover the period 1890-2018, with 96% of the data being from 1960 onwards. The database is rich in plants, birds and climatic events, but also includes insects, amphibians, reptiles and fungi. The database includes multiple events per species, such as the onset days of leaf unfolding and leaf fall for plants, and the days for first spring and last autumn occurrences for birds. The data were acquired using standardized methods by permanent staff of national parks and nature reserves (87% of the data) and members of a phenological observation network (13% of the data). The database is valuable for exploring how species respond in their phenology to climate change. Large-scale analyses of spatial variation in phenological response can help to better predict the consequences of species and community responses to climate change.Peer reviewe

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of bodysurface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2 ), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of endstage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.