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53. Alleviating the transit timing variation bias in transit surveys. I. RIVERS: Method and detection of a pair of resonant super-Earths around Kepler-1705

Author

Leleu, A., Chatel, G., Udry, S., Alibert, Y., Delisle, J. -B., and Mardling, R.

Subjects
Astrophysics - Earth and Planetary Astrophysics, Computer Science - Machine Learning
Abstract

Transit timing variations (TTVs) can provide useful information for systems observed by transit, as they allow us to put constraints on the masses and eccentricities of the observed planets, or even to constrain the existence of non-transiting companions. However, TTVs can also act as a detection bias that can prevent the detection of small planets in transit surveys that would otherwise be detected by standard algorithms such as the Boxed Least Square algorithm (BLS) if their orbit was not perturbed. This bias is especially present for surveys with a long baseline, such as Kepler, some of the TESS sectors, and the upcoming PLATO mission. Here we introduce a detection method that is robust to large TTVs, and illustrate its use by recovering and confirming a pair of resonant super-Earths with ten-hour TTVs around Kepler-1705. The method is based on a neural network trained to recover the tracks of low-signal-to-noise-ratio(S/N) perturbed planets in river diagrams. We recover the transit parameters of these candidates by fitting the light curve. The individual transit S/N of Kepler-1705b and c are about three times lower than all the previously known planets with TTVs of 3 hours or more, pushing the boundaries in the recovery of these small, dynamically active planets. Recovering this type of object is essential for obtaining a complete picture of the observed planetary systems, and solving for a bias not often taken into account in statistical studies of exoplanet populations. In addition, TTVs are a means of obtaining mass estimates which can be essential for studying the internal structure of planets discovered by transit surveys. Finally, we show that due to the strong orbital perturbations, it is possible that the spin of the outer resonant planet of Kepler-1705 is trapped in a sub- or super-synchronous spin-orbit resonance.

Published
2021
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55. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials

Author

Lynde, Charles, Guenther, Lyn, Sauder, Maxwell, Bissonnette, Robert, Rao, Jaggi, Day, Isaiah, Devani, Alim, Metelitsa, Andrei, Grewal, Parbeer, Molin, Sonja, Ruer-Mulard, Mireille, Giordano-Labadie, Françoise, Maillard, Hervé, Reguiai, Ziad, Bernier, Claire, Leleu, Camille, Seneschal, Julien, Staumont-Sallé, Delphine, Hubiche, Thomas, Jacobzone, Caroline, Khemis, Abdallah, Crépy, Marie-Noëlle, Worm, Margitta, Bauer, Andrea, Sell, Sabine, Ekanayake-Bohlig, Swarna, Pauser, Sylvia, Buhl, Timo, Schwinn, Andreas, Eberlein, Bernadette, Quist, Sven, Bauer, Boris, Peris, Ketty, Rossi, Maria Teresa, Fargnoli, Maria, Naldi, Luigi, Stingeni, Luca, Ferrucci, Silvia, Walecka-Herniczek, Irena, Krasowska, Dorota, Lesiak, Aleksandra, Okuniewska, Aleksandra, Pulka, Grażyna, Dyczek, Malgorzata, Kwiek, Bartlomiej, Czajkowski, Rafal, Myśliwiec, Hanna, Mohandas, Padma, Cliff, Sandeep, Warren, Richard, Cousen, Pippa, Johnston, Graham, Woolf, Richard, Papp, Kim, Adam, David, Toth, Darryl, Hong, Chih-ho, Turchin, Irina, Niakosari, Firouzeh, Poulos, Elena, Rivers, Jason, Ohayon, Jason, Gooderham, Melinda, Tjioe, Milan, Rustemeyer, Thomas, de Bruin-Weller, Marjolein S., Schuttelaar, Marie L.A., Molhoek, Judith, Oosting, Bert, Pinter, Andreas, Kaspari, Markus, Magnolo, Nina, Sebastian, Michael, Thaci, Diamant, Schliemann, Sibylle, Radny, Peter, Leitz, Nicolas, Tsianakas, Athanasios, Yazdi, Amir, Kamstrup, Maria, Sommerlund, Mette, Zachariae, Claus, Owczarek, Witold, Dudra-Jastrzebska, Monika, Reich, Adam, Kowalska-Oledzka, Elzbieta, Szepietowski, Jacek, Poznanska, Maria, Weglowska, Jolanta, Aerts, Olivier, Roquet-Gravy, Pierre-Paul, Lanssens, Sven, Castelijns, Francisca, Scheers, Christelle, Suys, Erwin, Kint, Bernard, Serra-Baldrich, Esther, Carrascosa, José Manuel, de la Cueva Dobao, Pablo, Izu, Rosa, Silvestre, Juan Francisco, Coto-Segura, Pablo, Fernández-Orland, Almudena, Warren, Richard B, Agner, Tove, Schuttelaar, Marie L A, Baranowski, Keith, Korn, Sofie, Kurvits, Merle, Plohberger, Ursula, and Strange Vest, Natacha

Published
2024
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56. Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial

Author

Moreau, Philippe, Hulin, Cyrille, Perrot, Aurore, Arnulf, Bertrand, Belhadj, Karim, Benboubker, Lotfi, Zweegman, Sonja, Caillon, Hélène, Caillot, Denis, Avet-Loiseau, Hervé, Delforge, Michel, Dejoie, Thomas, Facon, Thierry, Sonntag, Cécile, Fontan, Jean, Mohty, Mohamad, Jie, Kon-Siong, Karlin, Lionel, Kuhnowski, Frédérique, Lambert, Jérôme, Leleu, Xavier, Macro, Margaret, Orsini-Piocelle, Frédérique, Roussel, Murielle, Schiano de Colella, Jean Marc, van de Donk, Niels WCJ, Wuillème, Soraya, Broijl, Annemiek, Touzeau, Cyrille, Tiab, Mourad, Marolleau, Jean-Pierre, Meuleman, Nathalie, Vekemans, Marie-Christiane, Westerman, Matthijs, Klein, Saskia K, Levin, Mark-David, Offner, Fritz, Escoffre-Barbe, Martine, Eveillard, Jean-Richard, Garidi, Réda, Hua, Winnie, Wang, Jianping, Tuozzo, Alba, de Boer, Carla, Rowe, Melissa, Vanquickelberghe, Veronique, Carson, Robin, Vermeulen, Jessica, Corre, Jill, and Sonneveld, Pieter

Published
2024
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57. Listeria monocytogenes-associated spontaneous bacterial peritonitis in France: a nationwide observational study of 208 cases

Author

Abdou, Mohamed, Abdulhai, Ayman, Abdulhal, Ayman, Abel, Samy, Abergel, Armand, Aberrane, Saïd, Abraham, Bruno, Adler, Maxime, Agard, Christian, Agha-Mir, Ilhem, Aguilar, Claire, Agulles, Baptiste, Aldallal, Hamza, Alric, Laurent, Amiot, Xavier, Andrau, Pierre, Andrieux, Vladimir, Ansart, Séverine, Anty, Rodolphe, Archambeaud, Isabelle, Arem, Samir, Armand, Laurence, Aubailly, Lucie, Audibert, Juliette, Auguereau, Olivier, Auvray, Christelle, Aziz, Karime, Bachelier, Marie-Nadège, Bacquaert-Dufour, Karine, Badet, Françoise, Bahallah, Mohamed-Larbi, Balanant, Hélène, Baraduc, Régine, Bardis, Alexandre, Barraud, Olivier, Barrier, Jocelyn, Baudet, Antoine, Baumert, Thomas, Beaugerie, Laurent, Bébéar, Cécile, Becheur, Hakim, Bemer, Pascale, Benard, Caroline, Benezet, Marie-Pierre, Benmahammed, Mohammed, Bennouna, Jaafar, Benseddik, Zehaira, Bensimon, Pierre-Yves, Bental, Abdeslam, Berete, Aliou, Bergier, Jean-Michel, Berkani, Wacila, Bernardi, Franck, Bert, Frederic, Bertrou, Anne, Beuret, Pascal, Beurton-Chataigner, Isabelle, Beuscart, Claude, Beusnel, Christine, Bevilacqua, Sibylle, Beze, François, Bideau, Karine, Bidegain, Frédéric, Billon, Laura, Blaison, Gilles, Blanc, Michèle, Blanc, Pierre, Blanchi, Sophie, Blancho, Gilles, Bland, Stephane, Blondeau, Vincent, Boldron, Amale, Bon, Djemah, Bonacorsi, Stéphane, Bonzon, Lucas, Borderon, Anaïs, Botelho-Nevers, Elisabeth, Bottlaender, Jacques, Bouc-Boucher, Mathilde, Bouchaud, Olivier, Bougon, David, Boukelikha, Khaled, Bourlet, Thomas, Boussoukaya, Samy, Boutaleb, Hamza, Bouziges, Nicole, Bray, Philippe, Bréchet, Caroline, Bret, Laurent, Brieu, Nathalie, Briffaut, David, Brochet, Christine, Brulez-Des-Varannes, Stanislas, Brunel, Valéry, Brung-Lefebvre, Maud, Bureau, Christophe, Burucoa, Christophe, Buscail, Louis, Buzele, Rodolphe, Cadot, Catherine, Cadranel, Jean-Francois, Cady, Anne, Caillon, Jocelyne, Camiade, Sabine, Campillo, Bernard, Carbonnel, Franck, Carbonnelle, Etienne, Cardot-Martin, Émilie, Cariou, Marie-Estelle, Carles, Michel, Caron, Francois, Carrara-Delarue, Lucrecia, Carrier, Paul, Castang, Céline, Castellano, Inès, Cattoir, Vincent, Caubet, Olivier, Causse, Xavier, Chabrol, Amélie, Chanard, Emmanuel, Chatagnon, Thomas, Chazouilleres, Olivier, Chedanni, Halima, Chevrel, Pauline, Chirol, Catherine, Chirouze, Catherine, Chouquer, Renaud, Clavière, Christophe, Codreuil, Sylvain, Colardelle, Philippe, Combarnous, François, Commeau, Grégory, Cornillet, Anne, Corvec, Stephane, Costa, Yannick, Couderc, Philippe, Couffon, Caroline, Courivaud, Cécile, Courtade, Henri, Cruchant, Etienne, Cuen, David, Culard, Jean-François, Cung, Hong Ahn, Dahyot, Sandrine, D'Altéroche, Louis, Dao, Manh Thông, Darfeuil, Fabien, Darnaud, Céline, Daure, Sophie, De Grossouvre-Taillefer, Ludivine, Debriel, Dominique, Debrueres, Jacques, Decaens, Thomas, Decambron, Audrey, Decre-Grapinet, Dominique, Degand, Nicolas, Dehaye, Bruno, Delacour, Thierry, Delarbe, Jean-Marie, Delobel, Pierre, Delpierre, Éric, Delrez, René, Delvert, Didier, Demartino, Sylvie, Deniel, Marie-Clémence, Denis, Bernard, Derumeaux, Guy, Desroches, Marine, Dessein, Rodrigue, Devillez, Simon, Deweerdt, Didier, Diamantis, Sylvain, Diaz, Emmanuel, Didier, Raffenot, Dimartino, Vincent, Dion, Ludivine, Djemai, Mohand, Doche, Christophe, Donascimento, Maud, Dorval, Ian, Douala, Carol, Doucet-Populaire, Florence, Drouillat, Valérie, Dubée, Vincent, Dudermel, Anne-France, Dumont, Betty, Dupin, Clarisse, Dupont, Mathieu, Dupont, Philippe, Dupuy, Marion, Dupuychaffray, Jean-Pierre, Durand, Francois, Dusser, Pascale, Duval, Valérie, Duveau, Nicolas, El-Azouzi, Abdelghani, El-Gharras, Hynd, Elsendoorn, Antoine, Emile, Loïc, Epaulard, Olivier, Etchepare, Nicolas, Etienne, Jean-Pierre, Eveillard, Mathieu, Evers, Annie, Fach, Joelle, Faizoun, Claudia, Fangous, Marie-Sarah, Farmachidi, Jean Pierre, Fatome, Armelle, Faulques, Bernard, Faure, Karine, Felix, Charlotte, Ferec, Marc, Ferey, Janine, Ferracci, Serge, Feryn, Jean-Marc, Fesler, Pierre, Fiette, Hélène, Flevin, Emilie, Floch, Pauline, Fort, Eric, Fortineau, Nicolas, Fourcade, Jacques, Fraissinet, François, Franck, Patricia, Françoise, Thiebaut, Fratte, Serge, Galempoix, Jean-Marc, Garcera, Yves, Garcia, Anne, Garcon, Pierre, Garret, Charlotte, Gayet, Clement, Gazeau, Pierre, Gerber, Florence, Gilles, Raclot, Gillot, Jean-Michel, Goarant, Eric, Godreuil, Sylvain, Goret, Julien, Gorret, Julie, Goujard, Cecile, Goulenok, Thiphaine, Gournay, Jérôme, Gousseff, Marie, Goux, Alain, Graf, Emmanuelle, Grange, Jean-Didier, Gravet, Alain, Greder-Belan, Alix, Gronier, Olivier, Grosset, Marine, Guellouz, Sabra, Guenenna, Dalida, Guerbaa, Mohammed, Guerin, Meggie, Guerrot, Dominique, Guery, Benoit, Gugenheim, Jean, Guidet, Bertrand, Guiheneuf, Raphael, Guillet-Caruba, Christelle, Guimard, Yves, Guinard, Jérome, Guindre, Laure, Hagege, Albert, Hagege, Hervé, Haineaux, Paul-Arthur, Hamon, Rémy, Hassan, Firas, Hassine, Mélanie, Helie, Ludovic, Herber-Mayne, Anne, Hervio, Pascale, Héry-Arnaud, Geneviève, Hitoto, Hikombo, Hubsch, Théophile, Hunaut, Nicolas, Hurtova, Monika, Husson-Wetzel, Stéphanie, Hutin, Pascal, Izopet, Théo, Jacob, Jean-Louis, Jacomet, Christine, Jaffar-Bandjee, Marie-Christine, Janvier, Fréderic, Jaulhac, Benoît, Jaureguiberry, Stephane, Javaud, Nicolas, Jeannot, Katty, Joundy, Noureddine, Kacem, Moez, Karama, Rouis, Karsenti, David, Kempf, Marie, Khatibi, Sarah, Kikolski, Florence, Kittirath, Christine, Koch, Stephane, Kouatchet-Achille, Tchamba, Krummel, Yves, La Combe, Karine, Labarriere, Damien, Laberenne, Jean-Eric, Lacroix, Hervé, Ladrat, Laure, Lagarde, Stéphanie, Lagasse, Jean-Paul, Laggoune, Ahmed-Saïd, Lambare, Benedicte, Landgraf, Nathalie, Landraud, Luce, Laude, Jean-Francois, Laurent, François, Lavigne, Jean-Philippe, Lavoue, Vincent, Le Berre, Rozenn, Le Goff, Vallérie, Lebars, Hervé, Lebrun, Armandine, Lecapitaine, Anne-Lise, Lechat, Sylvie, Lecoustumier, Alain, Ledreau, Gérard, Lefevre, Benjamin, Leflon, Véronique, Lefort, Agnès, Legall, Florence, Legoff, Isabelle, Legrand, Eric, Lehello, Simon, Le-Henaff-Bourhis, Catherine, Leleu, Olivier, Lelievre, Lucie, Lemaignen, Adrien, Lemaire, Xavier, Le-Maout, Charles, Lemblé, Chantal, Lemeille, Yolande, Lemenand, Olivier, Lemeunier, Violaine, Lemeur, Yannick, Lemierre, Sylvia, Leotard, Sophie, Lepileur, Lucie, Letellier-Demonchy, Claire, Levecq, Hervé, Levy, Marc, Limal, Nicolas, Locher, Christophe, Lopez, Benjamin, Loron, Marie-Charlotte, Loulergue, Joelle, Loury-Larivière, Isabelle, Loustaud-Ratti, Véronique, Macchi, Valèrie, Machado, Moise, Madaule, Serge, Mainardi, Jean-Luc, Males, Silvija, Malherbe, Philippe, Maneglier, Benjamin, Marceau, Maryline, Marcel, Kévin, Marmonier, Alain, Martha, Benoît, Martin, Xavier, Martin-Blondel, Guillaume, Martinez, Camille, Marty, Fabrice, Marty, Patrick, Matray, Olivier, Maurin, Arnaud, Mazerand, Sandie, Mazouz, Nadia, Medevielle, Muriel, Mercat, Alain, Méreghetti, Laurent, Merzoug, Noureddine, Meziane, Ilham, Michaud, Anthony, Michel, Marc, Michel, Pierre, Mignard, Sophie, Milesi-Lecat, Anne-Marie, Mion, Mathieu, Mnasri, Nabil, Mohareb, Abdo, Mohib, Samir, Moindrot, Henri, Monlun, Eric, Montewis, Audrey, Morin, Thierry, Moussata, Driffa, Muller, Sandrine, Muzellec, Valérie, Nancey, Stéphane, Nassereddine, Ahmad, Naude, Sebastien, Neau, Didier, Ovidiu, Negru Calin, Ngo, Thuy, Ngwhotue, Marthe-Andree, Nivet, Patrick, Nordmann, Patrice, Nousbaum, Jean-Baptiste, Nouvel, Bernadette, Obled, Stephane, Oswald, Eric, Otto, Marie-Pierre, Pageaux, Georges-Philippe, Papin, Gregory, Parant, Fabrice, Patenotte, Arnaud, Paupard, Thierry, Pauwels, Arnaud, Pawlotsky, Jean Michel, Pelloux, Hervé, Perlemuter, Gabriel, Peron, Jean-Marie, Pestel-Caron, Martine, Peter, Natasha, Petillon, Sophie, Petit, Richard, Petitprez, Helene, Pettinelli, Francois, Phelip, Jean Marc, Philit, Jean-Baptiste, Phoutthasang, Valérie, Pialoux, Gilles, Piau-Couapel, Caroline, Pichard, Benoit, Pichon, Maxime, Picon-Coste, Magali, Picque, Marie, Pierson, Henri, Piques, Jean Francois, Piton, Béatrice, Planade, Orianne, Plassart, Claire, Plésiat, Patrick, Ploy, Marie-Cécile, Poubeau, Patrice, Pouderoux, Philippe, Pouedras, Pascal, Pourbaix, Annabelle, Poynard, Thierry, Preau, Florence, Pricope, Dumitrita, Queffelec, Gwenaëlle, Queneherve, Lucille, Quentin, Thomas, Raffenot, Didier, Rakotoniaina, Daniella, Ramanantsoa, Celine, Ramarijaona, Solofoniaina, Rami-Arab, Lila, Raulin, Olivia, Rebibou, Jean Michel, Renault, David, Rey, Philippe, Riche, Agnès, Rigaud, Jean Philippe, Rivière, Antoine, Rivière, Brigitte, Robert, Jérôme, Roblot, Pascal, Roger, Helene, Rolland, Christophe, Rondinaud, Emilie, Rosa-Hezode, Isabelle, Roubille, Martine, Rouquette, Olivier, Roux, Juliette, Ruimy, Raymond, Sachot-Ollivier, Sonia, Sailler, Laurent, Salamant, Sarah, Sarbu-Pop, Silvia, Sartre, Jacques, Schmitt, François, Scribe-Outtas, Myriam, Sefrioui, David, Sehouane, Rachid, Sekhri, Hacène, Serfaty, Lawrence, Sevin, Odile, Shawali, Cédric, Siladi, Souad, Silvain, Christine, Simon, Mireille, Simonet, Batiste, Sinayoko, Leila, Sirach, Estelle, Smati, Mustafa, Smets, Aurélie, Soltani, Dhaoui, Sommabere, André, Soulier-Guerin, Karine, Soulillou, Jean Paul, Soupison, Alain, Souply, Laurent, Soussy, Claude-James, Stampfli, Claire, Strullu, Bernard, Suatean, Diana, Tadjerouni, Nacer, Talarmin, Jean-Philippe, Tankovic, Jacques, Tarroun, Abdullah, Tchuenbou, Juliette, Teboul, Jean-Louis, Tedlaouti, Husni, Tellini, Charlotte, Thabut, Dominique, Thannberger, Philippe, Thiebault, Henri, Thiebaut, Françoise, Thomazeau, Joséphine, Tielman, Guillaume, Timsit, Jean-Francois, Tognon, Patrick, Tougeron, David, Toure, Fatouma, Tran, Albert, Tranvouez, Jean-Luc, Trésallet, Christophe, Trubert, Lise, Tsakiris, Laurent, Twizeyimana, Eterne, Vachee, Anne, Valade, Hélène, Valat, Isabelle, Vandendriessche, Anne, Vandermee, Nathalie, Vanheste, Marc, Varon, Emmanuelle, Vasse, Marc, Vasseur, Philippe, Vaucel, Elisabeth, Vauthier, Anne, Verdavaine-Loidreau, Delphine, Verdet, Charlotte, Verdon, Renaud, Vergnaud, Michel, Véziris, Nicolas, Vignaud, Guillaume, Viguier, Jérôme, Villemain, Marc, Villeneuve, Laurent, Vimont-Vicary, Alexandre, Vincent, Thomas, Vuillemenot, Jean-Baptiste, Walewski, Violaine, Warmoes, Elodie, Watry, Hélène, Weber, Jean-Christophe, Witz, Marie Thérèse, Woerther, Paul-Louis, Yazdanpanah, Yazdan, Zamfir, Oana, Zarka, Jonathan, Zavadil, Patrick, Zeboudj, Nabil, Zerbib, Franck, Blanchard, Florian, Henry, Benoît, Vijayaratnam, Sofieya, Canouï, Etienne, Moura, Alexandra, Thouvenot, Pierre, Bracq-Dieye, Hélène, Tessaud-Rita, Nathalie, Valès, Guillaume, Diakité, Andrée, Leclercq, Alexandre, Lecuit, Marc, and Charlier, Caroline

Published
2024
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58. Monitoring red wine maturation in oak barrels using 1H NMR-based metabolomics

Author

Inès Le Mao, Grégory Da Costa, Guillaume Leleu, and Tristan Richard

Subjects
Wine ageing, 1H NMR, targeted analysis, fingerprinting, Agriculture, Botany, QK1-989
Abstract

Wine maturation in oak barrels is a well-known winemaking practice that, among other things, brings roundness and complexity to wine. Studying wine evolution during barrel maturation is crucial to ensure wine quality. Red wines produced in a wine growing estate of the Bordeaux region were monitored after one and twelve months of maturation in oak barrels in the estate’s cellar. Wines were kept in oak casks from three different manufacturers. The evolution of the wine constituents during maturation was monitored by 1H NMR-based metabolomics combined with multivariate statistical analysis. NMR spectra were submitted to targeted and untargeted approaches. The wine maturation effects were thereby monitored and the discriminant metabolites identified. The wines analysed after one month of maturation exhibit higher contents of amino acids, catechin and epicatechin, acetoin and choline than the wines analysed twelve months after maturation; for their part, the latter wines showed higher contents of acetic acid, ethyl lactate, arabinose and glucose. In addition, significant differences were observed between the wines depending on the barrel manufacturers.

Published
2024

59. Generation of IPi001-A/B/C human induced pluripotent stem cell lines from healthy amniotic fluid cells

Author

Mikaël Boullé, Alix Boucharlat, Ambre Leleu, Céline Banal, Aurélie Coussement, Marcel Hollenstein, Frank Yates, Nathalie Lefort, and Fabrice Agou

Subjects
Biology (General), QH301-705.5
Abstract

Human induced Pluripotent Stem Cells (hiPSCs) represent an invaluable source of primary cells to investigate development, establish cell and disease models, provide material for regenerative medicine and allow more physiological high-content screenings. Here, we generated three healthy hiPSC control lines - IPi001-A/B/C - from primary amniotic fluid cells (AFCs), an infrequently used source of cells, which can be readily obtained from amniocentesis for the prenatal diagnosis of numerous genetic disorders. These AFCs were reprogrammed by non-integrative viral transduction. The resulting hiPSCs displayed normal karyotype and expressed classic pluripotency hallmarks.

Published
2024
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61. Coherent Ising Machines with Optical Error Correction Circuits

Author

Reifenstein, Sam, Kako, Satoshi, Khoyratee, Farad, Leleu, Timothée, and Yamamoto, Yoshihisa

Subjects
Quantum Physics
Abstract

We propose a network of open-dissipative quantum oscillators with optical error correction circuits. In the proposed network, the squeezed/anti-squeezed vacuum states of the constituent optical parametric oscillators below the threshold establish quantum correlations through optical mutual coupling, while collective symmetry breaking is induced above the threshold as a decision-making process. This initial search process is followed by a chaotic solution search step facilitated by the optical error correction feedback. As an optical hardware technology, the proposed coherent Ising machine (CIM) has several unique features, such as programmable all-to-all Ising coupling in the optical domain, directional coupling $(J_{ij} \neq J_{ji})$ induced chaotic behavior, and low power operation at room temperature. We study the performance of the proposed CIMs and investigate how the performance scales with different problem sizes. The quantum theory of the proposed CIMs can be used as a heuristic algorithm and efficiently implemented on existing digital platforms. This particular algorithm is derived from the truncated Wigner stochastic differential equation. We find that the various CIMs discussed are effective at solving many problem types, however the optimal algorithm is different depending on the instance. We also find that the proposed optical implementations have the potential for low energy consumption when implemented optically on a thin film LiNbO3 platform.

Published
2021

67. Risk factors for early mortality from lung cancer: evolution over the last 20 years in the French nationwide KBP cohorts

Author

Debieuvre, D., Asselain, B., Cortot, A., Couraud, S., Duval, Y., Falchero, L., Locher, C., Meyer, N., Molinier, O., Morel, H., Templement-Grangerat, D., Tredaniel, J., Olivier, Leleu, Caroline, Clarot, Stéphanie, Martinez, Marie, Bernardi, Etienne, Auvray, Julian, Pinsolle, Chantal, Decroisette, Dorine, Templement, Laure, Belmont, Thierry, Saelens, Amélie, Turlotte, Jérôme, Virally, Reda, Chikouche, Marielle, Sabatini, Sophie, Schneider, Jacky, Crequit, Faraj, Al Freijat, Baihas, Jarjour, Rym, Haouachi, Fethi, El Khanjari, Luc, Stoven, Pascal, Beynel, Vincent, Tack, Fatima, Meniai, Yannick, Duval, Hannah, Ghalloussi-Tebai, Claudia, Rizzo, Waad, Al Sheikh, Marguerite, Lepoulain Doubliez, Florence, Lamotte, François, Christiann, Patrick, Dumont, Philippe, Masson, Fréderic, Bigot, Hervé, Le Floch, Issam, Belhaj, Lionel, Moreau, Stéphanie, Dehette, Antoine, Belle, Lidia, Petit, Thomas, Laurent, Sandrine, Loutski-Vettese, Isabelle, Monnet, Jean-Bernard, Auliac, Edith, Maetz, Jean-Yves, Tavernier, Christian, Delafosse, Pierre-Alexandre, Hauss, Colette, Vincent, Mohamad, Jaafar, Jean Philippe, Kraemer, Laetitia, Chablais, Anne-Sophie, Bravard, Philippe, Bonnefoy, Christine, Lefoll, Alexandra, Bedossa, Élise, Redureau, Acya, Bizieux-Thaminy, Virginie, Levrat, Kevin, Fouet, Claire, Alizon, Cécile, Dujon, Hong, Rabut, Mihai, Popa, Jean, Quieffin, Pierre, Demontrond, Olivier, Molinier, François, Goupil, Kheir Eddine, Benmammar, Vanessa, Pante, Laurent, Portel, Anne-Sophie, Blanchet-Legens, Sébastien, Larive, Jacques, Le Treut, Herve, Pegliasco, Chrystèle, Locher, Séverine, Thomassin, Benoît, Godbert, Cécile, Maincent, Christophe, Perrin, Julie, Obert, Cyril, Maurer, David, Renault, Karim, Amrane, Didier, Debieuvre, Geoffroy, Milliet De Faverges, Andreea, Tudor, Maud, Russier, Hugues, Morel, Hugues, Francois, Jean, Tredaniel, Patrick Aldo, Renault, Magalie, Paysse, Anne-Marie, Chiappa, Romain, Corre, Laurent, Mosser, Sylvie, Julien, David, Nunes, Soraya, Bordier, Eric, Briens, Gwenaëlle, Le Garff, Clothilde, Marty, Bénédicte, Martignac, Charles, Dayen, Emmanuelle, Lecuyer, Philippe, Slaouti, Serge, Jeandeau, Christina, Delmas, Eric, Goarant, Marie, Tiercin, Jean-Michel, Peloni, Joelle, Courdeau-Labourie, Nicolae, Banciu, Anne-Sophie, Bugnet, Olivier, Bylicki, Marjorie, Picaud, Laurence, Thirard, Bertrand, Delclaux, Philippe, Brun, Marion, Nancy, David, Marquette, Gonzague, De Chabot, Pierre, Kuntz, Catherine, Marichy, Lionel, Falchero, Christine, Dussopt, Alexa, Mairovitz, Jean-Marc, Dot, Fanny, Magne, Hoang, T.C.T., Bravard, A.-S., Martinez, S., Le Garff, G., Jeandeau, S., Petit, L., Marquette, D., Amrane, K., Demontrond, P., Tiercin, M., Jarjour, B., Turlotte, A., Masson, P., Jaafar, M., and Hauss, P.-A.

Published
2024
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70. International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma

Author

Rodriguez-Otero, Paula, Usmani, Saad, Cohen, Adam D, van de Donk, Niels W C J, Leleu, Xavier, Gállego Pérez-Larraya, Jaime, Manier, Salomon, Nooka, Ajay K, Mateos, Maria Victoria, Einsele, Hermann, Minnema, Monique, Cavo, Michele, Derman, Benjamin A, Puig, Noemi, Gay, Francesca, Ho, P Joy, Chng, Wee-Joo, Kastritis, Efstathios, Gahrton, Gösta, Weisel, Katja, Nagarajan, Chandramouli, Schjesvold, Fredik, Mikhael, Joseph, Costa, Luciano, Raje, Noopur S, Zamagni, Elena, Hájek, Roman, Weinhold, Niels, Yong, Kwee, Ye, Jing Christine, Sidhana, Surbhi, Merlini, Giampaolo, Martin, Tom, Lin, Yi, Chari, Ajai, Popat, Rakesh, and Kaufman, Jonathan L

Published
2024
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71. The New Generation Planetary Population Synthesis (NGPPS). VI. Introducing KOBE: Kepler Observes Bern Exoplanets. Theoretical perspectives on the architecture of planetary systems: Peas in a pod

Author

Mishra, Lokesh, Alibert, Yann, Leleu, Adrien, Emsenhuber, Alexandre, Mordasini, Christoph, Burn, Remo, Udry, Stéphane, and Benz, Willy

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Solar and Stellar Astrophysics, Physics - Space Physics
Abstract

(abridged) Observations of exoplanets indicate the existence of several correlations in the architecture of planetary systems. Exoplanets within a system tend to be of similar size and mass, evenly spaced, and are often ordered in size and mass. Small planets are frequently packed in tight configurations, while large planets often have wider orbital spacing. Together, these correlations are called the peas in a pod trends in the architecture of planetary systems. In this paper these trends are investigated in theoretically simulated planetary systems and compared with observations. Whether these correlations emerge from astrophysical processes or the detection biases of the transit method is examined. Synthetic planetary system were simulated using the Generation III Bern Model. KOBE, a new computer code, simulates the geometrical limitations of the transit method and applies the detection biases and completeness of the Kepler survey. This allows simulated planetary systems to be compared with observations. The architecture of synthetic planetary systems, observed via KOBE, show the peas in a pod trends in good agreement with observations. These correlations are also present in the theoretical underlying population, from the Bern Model, indicating that these trends are probably of astrophysical origin. The physical processes involved in planet formation are responsible for the emergence of evenly spaced planets with similar sizes and masses. The size--mass similarity trends are primordial and originate from the oligarchic growth of protoplanetary embryos and the uniform growth of planets at early times. Later stages in planet formation allows planets within a system to grow at different rates, thereby decreasing these correlations. The spacing and packing correlations are absent at early times and arise from dynamical interactions., Comment: Accepted in A&A. Main body: 18 pages, 13 figures. Appendices: 7 pages, 3 figures. Code: https://github.com/exomishra/kobe

Published
2021
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72. Six transiting planets and a chain of Laplace resonances in TOI-178

Author

Leleu, A., Alibert, Y., Hara, N. C., Hooton, M. J., Wilson, T. G., Robutel, P., Delisle, J. -B., Laskar, J., Hoyer, S., Lovis, C., Bryant, E. M., Ducrot, E., Cabrera, J., Delrez, L., Acton, J. S., Adibekyan, V., Allart, R., Prieto, C. Allende, Alonso, R., Alves, D., Anderson, D. R., Angerhausen, D., Escudé, G. Anglada, Asquier, J., Barrado, D., Barros, S. C. C., Baumjohann, W., Bayliss, D., Beck, M., Beck, T., Bekkelien, A., Benz, W., Billot, N., Bonfanti, A., Bonfils, X., Bouchy, F., Bourrier, V., Boué, G., Brandeker, A., Broeg, C., Buder, M., Burdanov, A., Burleigh, M. R., Bárczy, T., Cameron, A. C., Chamberlain, S., Charnoz, S., Cooke, B. F., Van Damme, C. Corral, Correia, A. C. M., Cristiani, S., Damasso, M., Davies, M. B., Deleuil, M., Demangeon, O. D. S., Demory, B. -O., Di Marcantonio, P., Di Persio, G., Dumusque, X., Ehrenreich, D., Erikson, A., Figueira, P., Fortier, A., Fossati, L., Fridlund, M., Futyan, D., Gandolfi, D., Muñoz, A. García, Garcia, L. J., Gill, S., Gillen, E., Gillon, M., Goad, M. R., Hernández, J. I. González, Guedel, M., Günther, M. N., Haldemann, J., Henderson, B., Heng, K., Hogan, A. E., Isaak, K., Jehin, E., Jenkins, J. S., Jordán, A., Kiss, L., Kristiansen, M. H., Lam, K., Lavie, B., Etangs, A. Lecavelier des, Lendl, M., Lillo-Box, J., Curto, G. Lo, Magrin, D., Martins, C. J. A. P., Maxted, P. F. L., McCormac, J., Mehner, A., Micela, G., Molaro, P., Moyano, M., Murray, C. A., Nascimbeni, V., Nunes, N. J., Olofsson, G., Osborn, H. P., Oshagh, M., Ottensamer, R., Pagano, I., Pallé, E., Pedersen, P. P., Pepe, F. A., Persson, C. M., Peter, G., Piotto, G., Polenta, G., Pollacco, D., Poretti, E., Pozuelos, F. J., Queloz, D., Ragazzoni, R., Rando, N., Ratti, F., Rauer, H., Raynard, L., Rebolo, R., Reimers, C., Ribas, I., Santos, N. C., Scandariato, G., Schneider, J., Sebastian, D., Sestovic, M., Simon, A. E., Smith, A. M. S., Sousa, S. G., Sozzetti, A., Steller, M., Mascareño, A. Suárez, Szabó, Gy. M., Ségransan, D., Thomas, N., Thompson, S., Tilbrook, R. H., Triaud, A., Turner, O., Udry, S., Van Grootel, V., Venus, H., Verrecchia, F., Vines, J. I., Walton, N. A., West, R. G., Wheatley, P. J., Wolter, D., and Osorio, M. R. Zapatero

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

Determining the architecture of multi-planetary systems is one of the cornerstones of understanding planet formation and evolution. Resonant systems are especially important as the fragility of their orbital configuration ensures that no significant scattering or collisional event has taken place since the earliest formation phase when the parent protoplanetary disc was still present. In this context, TOI-178 has been the subject of particular attention since the first TESS observations hinted at a 2:3:3 resonant chain. Here we report the results of observations from CHEOPS, ESPRESSO, NGTS, and SPECULOOS with the aim of deciphering the peculiar orbital architecture of the system. We show that TOI-178 harbours at least six planets in the super-Earth to mini-Neptune regimes, with radii ranging from 1.152(-0.070/+0.073) to 2.87(-0.13/+0.14) Earth radii and periods of 1.91, 3.24, 6.56, 9.96, 15.23, and 20.71 days. All planets but the innermost one form a 2:4:6:9:12 chain of Laplace resonances, and the planetary densities show important variations from planet to planet, jumping from 1.02(+0.28/-0.23) to 0.177(+0.055/-0.061) times the Earth's density between planets c and d. Using Bayesian interior structure retrieval models, we show that the amount of gas in the planets does not vary in a monotonous way, contrary to what one would expect from simple formation and evolution models and unlike other known systems in a chain of Laplace resonances. The brightness of TOI-178 allows for a precise characterisation of its orbital architecture as well as of the physical nature of the six presently known transiting planets it harbours. The peculiar orbital configuration and the diversity in average density among the planets in the system will enable the study of interior planetary structures and atmospheric evolution, providing important clues on the formation of super-Earths and mini-Neptunes.

Published
2021
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79. Comparative Efficacy of Teclistamab Versus Current Treatments in Real-World Clinical Practice in the Prospective LocoMMotion Study in Patients with Triple-Class-Exposed Relapsed and/or Refractory Multiple Myeloma

Author

Moreau, Philippe, van de Donk, Niels W. C. J., Delforge, Michel, Einsele, Hermann, De Stefano, Valerio, Perrot, Aurore, Besemer, Britta, Pawlyn, Charlotte, Karlin, Lionel, Manier, Salomon, Leleu, Xavier, Weisel, Katja, Ghilotti, Francesca, Diels, Joris, Elsada, Ahmed, Morano, Raul, Strulev, Vadim, Pei, Lixia, Kobos, Rachel, Smit, Jennifer, Slavcev, Mary, and Mateos, Maria-Victoria

Published
2023
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80. Inflammation and oxidative stress markers in type 2 diabetes patients with Advanced Carotid atherosclerosis

Author

Louise Ménégaut, Aline Laubriet, Valentin Crespy, Damien Leleu, Thomas Pilot, Kevin Van Dongen, Jean-Paul Pais de Barros, Thomas Gautier, Jean-Michel Petit, Charles Thomas, Maxime Nguyen, Eric Steinmetz, and David Masson

Subjects
Diabetes, Atherosclerosis, Carotid, Inflammation, Arachidonic acid, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease. Methods The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes. Results In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1β, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes. Conclusion Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets. Trial registration The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).

Published
2023
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81. Long-term outcomes and renal responses following autologous hematopoietic stem cell transplantation for light chain deposition disease: a retrospective study on behalf of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Author

Laurent Garderet, Luuk Gras, Linda Koster, Liesbeth de Wreede, Rovira Montserrat, Laure Vincent, Roland Fenk, Kamaraj Karunanithi, Dries Deeren, Martin Kaufmann, Jürgen Kuball, Hakan Ozdogu, Maria Jesus Pascual Cascon, Jakob Passweg, Adam Rye, Urpu Salmenniemi, John Snowden, Charlotte Toftmann Hansen, Xavier Leleu, Lauris Gastaud, Joanna Drozd Sokolowska, Kavita Raj, Meral Beksac, Stefan Schönland, Patrick Hayden, and Donal McLornan

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

There is little long-term outcome data on the efficacy of autologous hematopoietic stem cell transplantation (ASCT) in light chain deposition disease (LCDD). We identified 51 LCDD patients in the EBMT registry who had undergone upfront ASCT between 1995 and 2021. The median serum creatinine was 280 μmol/L and 45% required renal replacement therapy (RRT) at time of transplant. The melphalan dose was 100mg/m2 in 23%, 140mg/m2 in 55% and 200 mg/m2 in 21%. The rate of very good partial response or better improved from 41% pre-transplant to 66% at Day +100 post-ASCT. In RRT-independent patients, there was a modest improvement in renal function within the first 3 months; the median eGFR increased from 44 to 51 ml/min/1.73 m2. There was no further change between 3 and 12 months post- ASCT. No patient who was RRT-independent at ASCT became RRT dependent by Day + 100 post-ASCT. Median follow-up post-ASCT was 84 months (IQR: 46-122). At 6-years post ASCT, overall survival (OS) was 88% (95% CI: 78-98%) and PFS was 44% (95% CI: 28-60%). The 2-year cumulative incidence of relapse and non-relapse mortality (NRM) was 17% (95% CI: 6-27%) and 2% (95% CI: 0-6%), respectively. The cumulative incidence of renal transplantation at 4 years after ASCT was 27% (95% CI 13-41) with renal transplantation performed between 6.3 and 52.9 months post-ASCT (median 24.7 months). ASCT represents a feasible option for LCDD patients even if RRT dependent at time of transplant. Outcomes are favourable with low NRM and good long-term OS.

Published
2024
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82. Belantamab mafodotin: an important treatment option for vulnerable patients with triple class exposed relapsed and/or refractory multiple myeloma

Author

Maria Victoria Mateos, Katja Weisel, Evangelos Terpos, Sossana Delimpasi, Efstathios Kastritis, Elena Zamagni, Michel Delforge, Enrique Ocio, Eirini Katodritou, Francesca Gay, Alessandra Larocca, Xavier Leleu, Paula Rodriguez Otero, Fredik Schjesvold, Michele Cavo, and Meletios A. Dimopoulos

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Not available.

Published
2024
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83. Isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone in patients with relapsed and refractory multiple myeloma: final overall survival analysis

Author

Paul G. Richardson, Aurore Perrot, Jesus San Miguel, Meral Beksac, Ivan Spicka, Xavier Leleu, Fredrik Schjesvold, Philippe Moreau, Meletios A. Dimopoulos, Shang-Yi Huang, Jiri Minarik, Michele Cavo, H. Miles Prince, Sandrine Macé, Rick Zhang, Franck Dubin, Mony Chenda Morisse, and Kenneth C. Anderson

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The primary and pre-specified updated analyses of ICARIA-MM (NCT02990338) demonstrated improved progression-free survival and a benefit in overall survival (OS) was reported with the addition of isatuximab, an anti-CD38 monoclonal antibody, to pomalidomide–dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma. Here, we report the final OS analysis. This multicenter, randomized, open-label, phase 3 study included patients who had received and failed ≥2 previous therapies, including lenalidomide and a proteasome inhibitor. Between January 10, 2017, and February 2, 2018, 307 patients were randomized (1:1) to isatuximab–pomalidomide– dexamethasone (Isa-Pd; n = 154) or Pd (n = 153), stratified based on age (3). At data cutoff for the final OS analysis after 220 OS events (January 27, 2022), median follow-up duration was 52.4 months. Median OS (95% confidence interval) was 24.6 months (20.3–31.3 months) with Isa-Pd and 17.7 months (14.4–26.2 months) with Pd (hazard ratio = 0.78; 95% CI, 0.59–1.02; 1-sided P = 0.0319). Despite subsequent daratumumab use in the Pd group and its potential benefit on PFS in the first subsequent therapy line, median PFS2 was significantly longer with Isa-Pd vs. Pd (17.5 vs. 12.9 months; log-rank 1-sided P = 0.0091). In this analysis, Isa-Pd continued to be efficacious and well tolerated after follow-up of approximately 52 months, contributing to a clinically meaningful, 6.9-month improvement in median overall survival in patients with relapsed/refractory multiple myeloma.

Published
2024
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84. Planetary system LHS 1140 revisited with ESPRESSO and TESS

Author

Lillo-Box, J., Figueira, P., Leleu, A., Acuña, L., Faria, J. P., Hara, N., Santos, N. C., Correia, A. C. M., Robutel, P., Deleuil, M., Barrado, D., Sousa, S., Bonfils, X., Mousis, O., Almenara, J. M., Astudillo-Defru, N., Marcq, E., Udry, S., Lovis, C., and Pepe, F.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

LHS 1140 is an M dwarf known to host two known transiting planets at orbital periods of 3.77 and 24.7 days. The external planet (LHS 1140 b) is a rocky super-Earth that is located in the middle of the habitable zone of this low-mass star, placing this system at the forefront of the habitable exoplanet exploration. We further characterize this system by improving the physical and orbital properties and search for additional planetary-mass components in the system, also exploring the possibility of co-orbitals. We collected 113 new radial velocity observations with ESPRESSO over a 1.5-year time span with an average photon-noise precision of 1.07 m/s. We determine new masses with a precision of 6% for LHS 1140 b ($6.48 \pm 0.46~M_{\oplus}$) and 9% for LHS 1140 c ($m_c=1.78 \pm 0.17~M_{\oplus}$), reducing by half the previously published uncertainties. Although both planets have Earth-like bulk compositions, the internal structure analysis suggests that LHS 1140 b might be iron-enriched. In both cases, the water content is compatible to a maximum fraction of 10-12% in mass, which is equivalent to a deep ocean layer of $779 \pm 650$ km for the habitable-zone planet LHS 1140 b. Our results also provide evidence for a new planet candidate in the system ($m_d= 4.8\pm1.1~M_{\oplus}$) on a ~78.9-day orbital period, which is detected through three independent methods. The analysis also allows us to discard other planets above 0.5 $M_{\oplus}$ for periods shorter than 10 days and above 2 $M_{\oplus}$ for periods up to one year. Finally, our analysis discards co-orbital planets of LHS 1140 b down to 1 $M_{\oplus}$. Indications for a possible co-orbital signal in LHS 1140 c are detected in both radial velocity and photometric data, however. The new characterization of the system make it a key target for atmospheric studies of rocky worlds at different stellar irradiations, Comment: 22 pages, 16 figures, 5 tables, published in A&A journal (see https://www.aanda.org/component/article?access=doi&doi=10.1051/0004-6361/202038922)

Published
2020
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85. Collective and synchronous dynamics of photonic spiking neurons

Author

Inagaki, Takahiro, Inaba, Kensuke, Leleu, Timothée, Honjo, Toshimori, Ikuta, Takuya, Enbutsu, Koji, Umeki, Takeshi, Kasahara, Ryoichi, Aihara, Kazuyuki, and Takesue, Hiroki

Subjects
Physics - Optics, Computer Science - Emerging Technologies, Nonlinear Sciences - Adaptation and Self-Organizing Systems
Abstract

Nonlinear dynamics of spiking neural networks has recently attracted much interest as an approach to understand possible information processing in the brain and apply it to artificial intelligence. Since information can be processed by collective spiking dynamics of neurons, the fine control of spiking dynamics is desirable for neuromorphic devices. Here we show that photonic spiking neurons implemented with paired nonlinear optical oscillators can be controlled to generate two modes of bio-realistic spiking dynamics by changing the optical pump amplitude. When they are coupled in a network, we found that the interaction between the photonic neurons induces an effective change in the pump amplitude depending on the order parameter that characterizes synchronization. The experimental results show that the effective change causes spontaneous modification of the spiking modes and firing rates of clustered neurons, and such collective dynamics can be utilized to realize efficient heuristics for solving NP-hard combinatorial optimization problems., Comment: 43 pages, 9 figures

Published
2020
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86. Scaling advantage of nonrelaxational dynamics for high-performance combinatorial optimization

Author

Leleu, Timothee, Khoyratee, Farad, Levi, Timothee, Hamerly, Ryan, Kohno, Takashi, and Aihara, Kazuyuki

Subjects
Physics - Computational Physics, Nonlinear Sciences - Chaotic Dynamics
Abstract

The development of physical simulators, called Ising machines, that sample from low energy states of the Ising Hamiltonian has the potential to drastically transform our ability to understand and control complex systems. However, most of the physical implementations of such machines have been based on a similar concept that is closely related to relaxational dynamics such as in simulated, mean-field, chaotic, and quantum annealing. We show that nonrelaxational dynamics that is associated with broken detailed balance and positive entropy production rate can accelerate the sampling of low energy states compared to that of conventional methods. By implementing such dynamics on field programmable gate array, we show that the nonrelaxational dynamics that we propose, called chaotic amplitude control, exhibits a scaling with problem size of the time to finding optimal solutions and its variance that is significantly smaller than that of relaxational schemes recently implemented on Ising machines.

Published
2020

87. Model-Size Reduction for Reservoir Computing by Concatenating Internal States Through Time

Author

Sakemi, Yusuke, Morino, Kai, Leleu, Timothée, and Aihara, Kazuyuki

Subjects
Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

Reservoir computing (RC) is a machine learning algorithm that can learn complex time series from data very rapidly based on the use of high-dimensional dynamical systems, such as random networks of neurons, called "reservoirs." To implement RC in edge computing, it is highly important to reduce the amount of computational resources that RC requires. In this study, we propose methods that reduce the size of the reservoir by inputting the past or drifting states of the reservoir to the output layer at the current time step. These proposed methods are analyzed based on information processing capacity, which is a performance measure of RC proposed by Dambre et al. (2012). In addition, we evaluate the effectiveness of the proposed methods on time-series prediction tasks: the generalized Henon-map and NARMA. On these tasks, we found that the proposed methods were able to reduce the size of the reservoir up to one tenth without a substantial increase in regression error. Because the applications of the proposed methods are not limited to a specific network structure of the reservoir, the proposed methods could further improve the energy efficiency of RC-based systems, such as FPGAs and photonic systems.

Published
2020
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88. Coherent Ising machines -- Quantum optics and neural network perspectives

Author

Yamamoto, Y., Leleu, T., Ganguli, S., and Mabuchi, H.

Subjects
Quantum Physics
Abstract

A coherent Ising machine (CIM) is a network of optical parametric oscillators (OPOs), in which the "strongest" collective mode of oscillation at well above threshold corresponds to an optimum solution of a given Ising problem. When a pump rate or network coupling rate is increased from below to above threshold, however, the eigenvectors with a smallest eigenvalue of Ising coupling matrix [J_ij] appear near threshold and impede the machine to relax to true ground states. Two complementary approaches to attack this problem are described here. One approach is to utilize squeezed/anti-squeezed vacuum noise of OPOs below threshold to produce coherent spreading over numerous local minima via quantum noise correlation, which could enable the machine to access either true ground states or excited states with eigen-energies close enough to that of ground states above threshold. The other approach is to implement real-time error correction feedback loop so that the machine migrates from one local minimum to another during an explorative search for ground states. Finally, a set of qualitative analogies connecting the CIM and traditional computer science techniques are pointed out. In particular, belief propagation and survey propagation used in combinatorial optimization are touched upon., Comment: 32 pages and 7 figures

Published
2020
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89. Coherent Ising machines with error correction feedback

Author

Kako, Satoshi, Leleu, Timothée, Inui, Yoshitaka, Khoyratee, Farad, Reifenstein, Sam, and Yamamoto, Yoshihisa

Subjects
Physics - Optics, Computer Science - Emerging Technologies, Nonlinear Sciences - Chaotic Dynamics
Abstract

A non-equilibrium open-dissipative neural network, such as a coherent Ising machine based on mutually coupled optical parametric oscillators, has been proposed and demonstrated as a novel computing machine for hard combinatorial optimization problems. However, there are two challenges in the previously proposed approach: (1) The machine can be trapped by local minima which increases exponentially with problem size and (2) the machine fails to map a target Hamiltonian correctly on the loss landscape of a neural network due to oscillator amplitude heterogeneity. Both of them lead to erroneous solutions rather than correct answers. In this paper, we show that it is possible to overcome these two problems partially but simultaneously by introducing error detection and correction feedback mechanism. The proposed machine achieves efficient sampling of degenerate ground states and low-energy excited states via its inherent migration property during a solution search process., Comment: 12 pages, 7 figures

Published
2020
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90. On the impact of tides on the transit-timing fits to the TRAPPIST-1 system

Author

Bolmont, Emeline, Demory, Brice-Olivier, Blanco-Cuaresma, Sergi, Agol, Eric, Grimm, Simon L., Auclair-Desrotour, Pierre, Selsis, Franck, and Leleu, Adrien

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

Transit Timing Variations, or TTVs, can be a very efficient way of constraining masses and eccentricities of multi-planet systems. Recent measurements of the TTVs of TRAPPIST-1 led to an estimate of the masses of the planets, enabling an estimate of their densities. A recent TTV analysis using data obtained in the past two years yields a 34% and 13% increase in mass for TRAPPIST-1b and c, respectively. In most studies to date, a Newtonian N-body model is used to fit the masses of the planets, while sometimes general relativity is accounted for. Using the Posidonius N-body code, we show that in the case of the TRAPPIST-1 system, non-Newtonian effects might be also relevant to correctly model the dynamics of the system and the resulting TTVs. In particular, using standard values of the tidal Love number $k_2$ (accounting for the tidal deformation) and the fluid Love number $k_{2f}$ (accounting for the rotational flattening) leads to differences in the TTVs of TRAPPIST-1b and c similar to the differences caused by general relativity. We also show that relaxing the values of tidal Love number $k_2$ and the fluid Love number $k_{2f}$ can lead to TTVs which differ by as much as a few 10~s on a $3-4$-year timescale, which is a potentially observable level. The high values of the Love numbers needed to reach observable levels for the TTVs could be achieved for planets with a liquid ocean, which, if detected, might then be interpreted as a sign that TRAPPIST-1b and TRAPPIST-1c could have a liquid magma ocean. For TRAPPIST-1 and similar systems, the models to fit the TTVs should potentially account for general relativity, for the tidal deformation of the planets, for the rotational deformation of the planets and, to a lesser extent, for the rotational deformation of the star, which would add up to 7x2+1 = 15 additional free parameters in the case of TRAPPIST-1., Comment: 7 pages, 3 figures. Accepted for publication in Astronomy & Astrophysics

Published
2020
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91. Prognostic impact of translocation t(14;16) in multiple myeloma according to the presence of additional genetic lesions

Author

Schavgoulidze, Anaïs, Perrot, Aurore, Cazaubiel, Titouan, Leleu, Xavier, Montes, Lydia, Jacquet, Caroline, Belhadj, Karim, Brechignac, Sabine, Frenzel, Laurent, Chalopin, Thomas, Rey, Philippe, Schiano de Collela, Jean-Marc, Dib, Mamoun, Caillot, Denis, Macro, Margaret, Fontan, Jean, Buisson, Laure, Pavageau, Luka, Roussel, Murielle, Manier, Salomon, Mohty, Mohamad, Martinet, Ludovic, Avet-Loiseau, Hervé, and Corre, Jill

Published
2023
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92. Correction: Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study

Author

Martin, Thomas, Dimopoulos, Meletios-Athanasios, Mikhael, Joseph, Yong, Kwee, Capra, Marcelo, Facon, Thierry, Hajek, Roman, Špička, Ivan, Baker, Ross, Kim, Kihyun, Martinez, Gracia, Min, Chang-Ki, Pour, Ludek, Leleu, Xavier, Oriol, Albert, Koh, Youngil, Suzuki, Kenshi, Casca, France, Macé, Sandrine, Risse, Marie-Laure, and Moreau, Philippe

Published
2023
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95. Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study

Author

Martin, Thomas, Dimopoulos, Meletios-Athanasios, Mikhael, Joseph, Yong, Kwee, Capra, Marcelo, Facon, Thierry, Hajek, Roman, Špička, Ivan, Baker, Ross, Kim, Kihyun, Martinez, Gracia, Min, Chang-Ki, Pour, Ludek, Leleu, Xavier, Oriol, Albert, Koh, Youngil, Suzuki, Kenshi, Casca, France, Macé, Sandrine, Risse, Marie-Laure, and Moreau, Philippe

Published
2023
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96. Prognostic impact of translocation t(14;16) in multiple myeloma according to the presence of additional genetic lesions

Author

Anaïs Schavgoulidze, Aurore Perrot, Titouan Cazaubiel, Xavier Leleu, Lydia Montes, Caroline Jacquet, Karim Belhadj, Sabine Brechignac, Laurent Frenzel, Thomas Chalopin, Philippe Rey, Jean-Marc Schiano de Collela, Mamoun Dib, Denis Caillot, Margaret Macro, Jean Fontan, Laure Buisson, Luka Pavageau, Murielle Roussel, Salomon Manier, Mohamad Mohty, Ludovic Martinet, Hervé Avet-Loiseau, and Jill Corre

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
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97. Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk.

Author

Richard, Shambavi, Chari, Ajai, Delimpasi, Sosana, Simonova, Maryana, Spicka, Ivan, Pour, Ludek, Kriachok, Iryna, Dimopoulos, Meletios, Pylypenko, Halyna, Auner, Holger, Leleu, Xavier, Usenko, Ganna, Hajek, Roman, Benjamin, Reuben, Dolai, Tuphan, Sinha, Dinesh, Venner, Christopher, Garg, Mamta, Stevens, Don, Quach, Hang, Jagannath, Sundar, Moreau, Phillipe, Levy, Moshe, Badros, Ashraf, Anderson, Larry, Bahlis, Nizar, Facon, Thierry, Mateos, Maria, Cavo, Michele, Chang, Hua, Landesman, Yosef, Chai, Yi, Arazy, Melina, Shah, Jatin, Shacham, Sharon, Kauffman, Michael, Grosicki, Sebastian, and Richardson, Paul

Subjects
Adult, Aged, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Bortezomib, Cytogenetic Analysis, Dexamethasone, Female, Humans, Hydrazines, Male, Middle Aged, Multiple Myeloma, Progression-Free Survival, Treatment Outcome, Triazoles, Young Adult
Abstract

In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1-3 prior regimens were randomized to once-weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib-dexamethasone (XVd) or twice-weekly bortezomib-dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high-risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n = 70; Vd, n = 71), and 261 (64.9%) exhibited standard-risk cytogenetics (XVd, n = 125; Vd, n = 136). Among patients with high-risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p = 0.004). In the standard-risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.

Published
2021

98. Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US.

Author

Davies, Faith, Rifkin, Robert, Costello, Caitlin, Morgan, Gareth, Usmani, Saad, Abonour, Rafat, Palumbo, Antonio, Romanus, Dorothy, Hajek, Roman, Terpos, Evangelos, Cherepanov, Dasha, Stull, Dawn, Huang, Hui, Leleu, Xavier, Berdeja, Jesus, Lee, Hans, Weisel, Katja, Thompson, Michael, Boccadoro, Mario, Zonder, Jeffrey, Cook, Gordon, Puig, Noemi, Vela-Ojeda, Jorge, Farrelly, Eileen, Raju, Aditya, Blazer, Marlo, and Chari, Ajai

Subjects
Bortezomib, Carfilzomib, Daratumumab, Ixazomib, Lenalidomide, Pomalidomide, Proteasome inhibitor triplet therapy, Real-world, Relapsed refractory multiple myeloma, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Boron Compounds, Bortezomib, Female, Glycine, Humans, Male, Middle Aged, Multiple Myeloma, Neoplasm Recurrence, Local, Oligopeptides, Retrospective Studies, Treatment Outcome
Abstract

Multiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optums deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.

Published
2021

99. Prognostic models for short-term annual risk of severe complications and mortality in patients living with type 2 diabetes using a national medical claim database

Author

Alexandre Vimont, Sophie Béliard, René Valéro, Henri Leleu, and Isabelle Durand-Zaleski

Subjects
Type 2 diabetes, Cardiovascular disease, Risk prediction, Health insurance claims, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Objective Prognostic models in patients living with diabetes allow physicians to estimate individual risk based on medical records and biological results. Clinical risk factors are not always all available to evaluate these models so that they may be complemented with models from claims databases. The objective of this study was to develop, validate and compare models predicting the annual risk of severe complications and mortality in patients living with type 2 diabetes (T2D) from a national claims data. Research design and methods Adult patients with T2D were identified in a national medical claims database through their history of treatments or hospitalizations. Prognostic models were developed using logistic regression (LR), random forest (RF) and neural network (NN) to predict annual risk of outcome: severe cardiovascular (CV) complications, other severe T2D-related complications, and all-cause mortality. Risk factors included demographics, comorbidities, the adjusted Diabetes Severity and Comorbidity Index (aDSCI) and diabetes medications. Model performance was assessed using discrimination (C-statistics), balanced accuracy, sensibility and specificity. Results A total of 22,708 patients with T2D were identified, with mean age of 68 years and average duration of T2D of 9.7 years. Age, aDSCI, disease duration, diabetes medications and chronic cardiovascular disease were the most important predictors for all outcomes. Discrimination with C-statistic ranged from 0.715 to 0.786 for severe CV complications, from 0.670 to 0.847 for other severe complications and from 0.814 to 0.860 for all-cause mortality, with RF having consistently the highest discrimination. Conclusion The proposed models reliably predict severe complications and mortality in patients with T2D, without requiring medical records or biological measures. These predictions could be used by payers to alert primary care providers and high-risk patients living with T2D.

Published
2023
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100. Experimental observation of chimera states in spiking neural networks based on degenerate optical parametric oscillators

Author

Tumi Makinwa, Kensuke Inaba, Takahiro Inagaki, Yasuhiro Yamada, Timothée Leleu, Toshimori Honjo, Takuya Ikuta, Koji Enbutsu, Takeshi Umeki, Ryoichi Kasahara, Kazuyuki Aihara, and Hiroki Takesue

Subjects
Astrophysics, QB460-466, Physics, QC1-999
Abstract

Abstract The phenomenon of partial synchronization has attracted significant interest in the field of nonlinear dynamics, largely due to observations of related phenomena in real-world situations. In particular, the coexistence of synchronized and desynchronized phases, known as a chimera state, has been the subject of intense study. In this work, we experimentally demonstrate that networks of identical photonic spiking neurons based on coupled degenerate optical parametric oscillators can exhibit various chimera states in which, depending on their local synchronization and desynchronization, different kinds of spiking dynamics can develop in a self-organized manner. Even when only a static interaction is implemented, the spiking mode of photonic neurons can be spontaneously and adaptively changed between the Class-I and Class-II modes classified by A. L. Hodgkin. This spontaneous spiking-mode shift induces a significant change in the spiking frequency despite all neurons having the same natural spiking frequency, which encourages the generation of chimera states.

Published
2023
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