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6. Microdeletion at chromosome 4q21 defines a new emerging syndrome with marked growth restriction, mental retardation and absent or severely delayed speech

Author

Bonnet, F., Andrieux, A, Béri-Dexheimer, D, Leheup, L, Boute, B, Manouvrier, M, Delobel, D, Copin, C., Receveur, A., Mathieu, M., Thiriez, G., Le Caignec, L, David, D, de Blois, M, Malan, M, Philippe, P., Cormier-Daire, D, Colleaux, Laurence, Flori, F, Dollfus, D, Pelletier, P, Thauvin-Robinet, C., Masurel-Paulet, P, Faivre, F, Tardieu, M., Bahi-Buisson, N., Callier, P., Mugneret, F., Edery, P., Jonveaux, P., Sanlaville, D., Andrieux, J., Beri-Dexheimer, M., Leheup, B., Boute, O., Manouvrier, S., Delobel, B., Copin, H., Le Caignec, C., David, A., de Blois, C., Malan, V., Philippe, A., Cormier-Daire, V., Flori, E., Dollfus, H., Pelletier, V., Masurel-Paulet, A., Faivre, L., CHU Bordeaux [Bordeaux], UMR 1011, Institut National de la Santé et de la Recherche Médicale (INSERM), Ouvrages hydrauliques et hydrologie (UR OHAX), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire de cytogénétique (CHU de Dijon), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Génétique Clinique, Hôpital Femme Mère Enfant, Centre Hospitalier Universitaire de Lyon, Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Microarray, Chromosome Disorders, 0302 clinical medicine, MESH: Child, MESH: Syndrome, MESH: In Situ Hybridization, Fluorescence, Child, Genetics (clinical), Growth Disorders, In Situ Hybridization, Fluorescence, Genetics, 0303 health sciences, Comparative Genomic Hybridization, MESH: Chromosome Disorders, Syndrome, Microdeletion syndrome, MESH: Growth Disorders, Phenotype, MESH: Infant, 3. Good health, MESH: Young Adult, Child, Preschool, Female, Chromosome Deletion, Chromosomes, Human, Pair 4, Haploinsufficiency, MESH: Chromosomes, Human, Pair 4, MESH: Abnormalities, Multiple, Adolescent, MESH: Chromosome Deletion, Biology, MESH: Language Development Disorders, MESH: Intellectual Disability, 03 medical and health sciences, Young Adult, Gene mapping, Intellectual Disability, medicine, Humans, Abnormalities, Multiple, Language Development Disorders, Genetically modified animal, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Child, Preschool, Infant, medicine.disease, MESH: Male, Developmental disorder, MESH: Comparative Genomic Hybridization, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Female, 030217 neurology & neurosurgery, Comparative genomic hybridization
Abstract

International audience; BACKGROUND Genome-wide screening of large patient cohorts with mental retardation using microarray-based comparative genomic hybridisation (array-CGH) has recently led to identification several novel microdeletion and microduplication syndromes. METHODS Owing to the national array-CGH network funded by the French Ministry of Health, shared information about patients with rare disease helped to define critical intervals and evaluate their gene content, and finally determine the phenotypic consequences of genomic array findings. RESULTS In this study, nine unrelated patients with overlapping de novo interstitial microdeletions involving 4q21 are reported. Several major features are common to all patients, including neonatal muscular hypotonia, severe psychomotor retardation, marked progressive growth restriction, distinctive facial features and absent or severely delayed speech. The boundaries and the sizes of the nine deletions are different, but an overlapping region of 1.37 Mb is defined; this region contains five RefSeq genes: PRKG2, RASGEF1B, HNRNPD, HNRPDL and ENOPH1. DISCUSSION Adding new individuals with similar clinical features and 4q21 deletion allowed us to reduce the critical genomic region encompassing two genes, PRKG2 and RASGEF1B. PRKG2 encodes cGMP-dependent protein kinase type II, which is expressed in brain and in cartilage. Information from genetically modified animal models is pertinent to the clinical phenotype. RASGEF1B is a guanine nucleotide exchange factor for Ras family proteins, and several members have been reported as key regulators of actin and microtubule dynamics during both dendrite and spine structural plasticity. CONCLUSION Clinical and molecular delineation of 4q21 deletion supports a novel microdeletion syndrome and suggests a major contribution of PRKG2 and RASGEF1B haploinsufficiency to the core phenotype.

Published
2010

14. Unveiling the strong interaction among hadrons at the LHC

Author

Acharya, Shreyasi, Adamova, Dagmar, Ahn, Sang Un, Bhattacharjee, Buddhadeb, Yurchenko, Volodymyr, Zaccolo, Valentina, Zaman, Ali, Zampolli, Chiara, Correia Zanoli, Henrique Jose, Zardoshti, Nima, Zarochentsev, Andrey, Zavada, Petr, Zavyalov, Nikolay, Zbroszczyk, Hanna Paulina, Bianchi, Antonio, Zhalov, Mikhail, Zhang, Song, Zhang, Xiaoming, Zhang, Zuman, Zherebchevskii, Vladimir, Yu, Zhi, Zhou, Daicui, Zhou, You, Zhou, Zhuo, Zhu, Jianhui, Bianchi, Livio, Zhu, Ya, Zichichi, Antonino, Zinovjev, Gennady, Zurlo, Nicola, ALICE Collaboration, Bianchi, Nicola, Bielcik, Jaroslav, Bielcikova, Jana, Bilandzic, Ante, Biro, Gabor, Biswas, Rathijit, Biswas, Saikat, Akbar, Zaenal, Blair, Justin Thomas, Blau, Dmitry, Blume, Christoph, Boca, Gianluigi, Bock, Friederike, Bogdanov, Alexey, Boi, Stefano, Bok, Jeongsu, Boldizsar, Laszlo, Bolozdynya, Alexander, Akindinov, Alexander, Bombara, Marek, Bonomi, Germano, Borel, Herve, Borissov, Alexander, Bossi, Hannah, Botta, Elena, Bratrud, Lars, Braun-munzinger, Peter, Bregant, Marco, Broz, Michal, Al-turany, Mohammad, Bruna, Elena, Bruno, Giuseppe Eugenio, Buckland, Matthew Daniel, Budnikov, Dmitry, Buesching, Henner, Bufalino, Stefania, Bugnon, Ophelie, Buhler, Paul Alois, Buncic, Predrag, Buthelezi, Edith Zinhle, Alam, Sk Noor, Bashir Butt, Jamila, Bysiak, Sebastian Adam, Caffarri, Davide, Caliva, Alberto, Calvo Villar, Ernesto, Mejia Camacho, Juan Manuel, Soto Camacho, Rabi, Camerini, Paolo, De Moraes Canedo, Fabio, Capon, Aaron Allan, Silva De Albuquerque, Danilo, Carnesecchi, Francesca, Caron, Robin Albert Andre, Castillo Castellanos, Javier Ernesto, Castro, Andrew John, Casula, Ester Anna Rita, Catalano, Fabio, Ceballos Sanchez, Cesar, Chakraborty, Pritam, Chandra, Sinjini, Chang, Wan, Aleksandrov, Dmitry, Chapeland, Sylvain, Chartier, Marielle, Chattopadhyay, Subhasis, Chattopadhyay, Sukalyan, Chauvin, Alex Henri Jean, Cheshkov, Cvetan Valeriev, Cheynis, Brigitte, Chibante Barroso, Vasco Miguel, Dobrigkeit Chinellato, David, Cho, Soyeon, Alessandro, Bruno, Chochula, Peter, Chowdhury, Tasnuva, Christakoglou, Panagiotis, Christensen, Christian Holm, Christiansen, Peter, Chujo, Tatsuya, Cicalo, Corrado, Cifarelli, Luisa, De Cilladi, Lorenzo, Cindolo, Federico, Alfanda, Haidar Mas'ud, Ciupek, Michael Rudolf, Clai, Giulia, Cleymans, Jean Willy Andre, Colamaria, Fabio Filippo, Colella, Domenico, Collu, Alberto, Colocci, Manuel, Concas, Matteo, Conesa Balbastre, Gustavo, Conesa Del Valle, Zaida, Alfaro Molina, Jose Ruben, Contin, Giacomo, Contreras Nuno, Jesus Guillermo, Cormier, Thomas Michael, Corrales Morales, Yasser, Cortese, Pietro, Cosentino, Mauro Rogerio, Costa, Filippo, Costanza, Susanna, Crochet, Philippe, Cuautle Flores, Eleazar, Adler, Alexander, Ali, Bushra, Cui, Pengyao, Cunqueiro Mendez, Leticia, Dabrowski, Daniel, Dahms, Torsten, Dainese, Andrea, Damas, Florian Paul Andre, Danisch, Meike Charlotte, Danu, Andrea, Das, Debasish, Das, Indranil, Ali, Yasir, Das, Prottay, Das, Prottoy, Das, Supriya, Dash, Ajay Kumar, Dash, Sadhana, De, Sudipan, De Caro, Annalisa, De Cataldo, Giacinto, De Cuveland, Jan, De Falco, Alessandro, Alici, Andrea, De Gruttola, Daniele, De Marco, Nora, De Pasquale, Salvatore, Deb, Suman, Franz Degenhardt, Hermann, Deja, Kamil Rafal, Deloff, Andrzej, Delsanto, Silvia, Deng, Wenjing, Dhankher, Preeti, Alizadehvandchali, Negin, Di Bari, Domenico, Di Mauro, Antonio, Arteche Diaz, Raul, Dietel, Thomas, Raisig, Pascal, Ding, Yanchun, Divia, Roberto, Dixit, Dhruv Utpalkumar, Djuvsland, Oeystein, Dmitrieva, Uliana, Alkin, Anton, Dobrin, Alexandru Florin, Donigus, Benjamin, Dordic, Olja, Dubey, Anand Kumar, Dubla, Andrea, Dudi, Sandeep, Mallick, Dukhishyam, Dupieux, Pascal, Ehlers Iii, Raymond James, Eikeland, Viljar Nilsen, Alme, Johan, Elia, Domenico, Erazmus, Barbara Ewa, Erhardt, Filip, Erokhin, Andrey, Ersdal, Magnus Rentsch, Espagnon, Bruno, Eulisse, Giulio, Evans, David, Evdokimov, Sergey, Fabbietti, Laura, Alt, Torsten, Faggin, Mattia, Faivre, Julien, Fan, Feng, Fantoni, Alessandra, Fasel, Markus, Fecchio, Pietro, Feliciello, Alessandro, Feofilov, Grigorii, Fernandez Tellez, Arturo, Ferrero, Andrea, Altenkamper, Lucas, Ferretti, Alessandro, Festanti, Andrea, Feuillard, Victor Jose Gaston, Figiel, Jan, Filchagin, Sergey, Finogeev, Dmitry, Fionda, Fiorella, Fiorenza, Gabriele, Flor, Fernando Antonio, Flores, Amanda Nicole, Altsybeev, Igor, Foertsch, Siegfried Valentin, Foka, Panagiota, Fokin, Sergey, Fragiacomo, Enrico, Frankenfeld, Ulrich Michael, Fuchs, Ulrich, Furget, Christophe, Furs, Artur, Fusco Girard, Mario, Gaardhoeje, Jens Joergen, Anaam, Mustafa, Gagliardi, Martino, Gago Medina, Alberto Martin, Gal, Arthur Willem Jean, Duarte Galvan, Carlos, Ganoti, Paraskevi, Garabatos Cuadrado, Jose, Alvarado Garcia, Jesus Ricardo, Garcia-solis, Edmundo Javier, Garg, Kunal, Gargiulo, Corrado, Adolfsson, Jonatan, Andrei, Cristian, Garibli, Aydan, Garner, Katharina, Gasik, Piotr Jan, Gauger, Erin Frances, De Leone Gay, Maria Beatriz, Germain, Marie, Ghosh, Jhuma, Ghosh, Premomoy, Ghosh, Sanjay Kumar, Giacalone, Marco, Andreou, Dimitra, Gianotti, Paola, Giubellino, Paolo, Giubilato, Piero, Glaenzer, Aude Marie Camille, Glassel, Peter, Gomez Ramirez, Andres, Gonzalez, Victor, Gonzalez Trueba, Laura Helena, Gorbunov, Sergey, Gorlich, Lidia Maria, Andronic, Anton, Goswami, Ankita, Gotovac, Sven, Grabski, Varlen, Graczykowski, Lukasz Kamil, Graham, Katie Leanne, Greiner, Leo Clifford, Grelli, Alessandro, Grigoras, Costin, Grigoryev, Vladislav, Grigoryan, Ara, Angeletti, Massimo, Grigoryan, Smbat, Groettvik, Ola Slettevoll, Grosa, Fabrizio, Grosse-oetringhaus, Jan Fiete, Grosso, Raffaele, Guernane, Rachid, Guittiere, Manuel, Gulbrandsen, Kristjan Herlache, Gunji, Taku, Gupta, Anik, Anguelov, Venelin, Gupta, Ramni, Bautista Guzman, Irais, Haake, Rudiger, Habib, Michael Karim, Hadjidakis, Cynthia Marie, Hamagaki, Hideki, Hamar, Gergoe, Hamid, Mohammed, Hannigan, Ryan Patrick, Haque, Md Rihan, Anson, Christopher Daniel, Harlenderova, Alena, Harris, John William, Harton, Austin Vincent, Hasenbichler, Jan Anton, Hassan, Hadi, Hassan, Qamar Ul, Hatzifotiadou, Despina, Hauer, Philip, Havener, Laura Brittany, Hayashi, Shinichi, Anticic, Tome, Heckel, Stefan Thomas, Hellbar, Ernst, Helstrup, Haavard, Herghelegiu, Andrei Ionut, Herman, Tomas, Gonzalez Hernandez, Emma, Herrera Corral, Gerardo Antonio, Herrmann, Florian, Hetland, Kristin Fanebust, Hillemanns, Hartmut, Antinori, Federico, Hills, Christopher, Hippolyte, Boris, Hohlweger, Bernhard, Honermann, Jan, Horak, David, Hornung, Andrea, Hornung, Sebastian, Hosokawa, Ritsuya, Hristov, Peter Zahariev, Huang, Chun-lu, Antonioli, Pietro, Hughes, Charles, Huhn, Patrick, Humanic, Thomas, Hushnud, Hushnud, Husova, Lucia Anna, Hussain, Nur, Hussain, Syed Asad, Hutter, Dirk, Iddon, James Philip, Ilkaev, Radiy, Apadula, Nicole, Ilyas, Hira, Inaba, Motoi, Innocenti, Gian Michele, Ippolitov, Mikhail, Isakov, Artem, Islam, Md Samsul, Ivanov, Marian, Ivanov, Vladimir, Izucheev, Vladimir, Jacak, Barbara, Aggarwal, Madan Mohan, Aphecetche, Laurent Bernard, Jacazio, Nicolo, Jacobs, Peter Martin, Jadlovska, Slavka, Jadlovsky, Jan, Jaelani, Syaefudin, Jahnke, Cristiane, Jakubowska, Monika Joanna, Janik, Malgorzata Anna, Janson, Thomas, Jercic, Marko, Appelshaeuser, Harald, Jevons, Oliver Thomas, Jin, Muqing, Jonas, Florian, Jones, Peter Graham, Jung, Jerome, Jung, Michael, Jusko, Anton, Kalinak, Peter, Kalweit, Alexander Philipp, Kaplin, Vladimir, Arcelli, Silvia, Kar, Somnath, Karasu Uysal, Ayben, Karatovic, David, Karavichev, Oleg, Karavicheva, Tatiana, Karczmarczyk, Przemyslaw, Karpechev, Evgeny, Kazantsev, Andrey, Kebschull, Udo Wolfgang, Keidel, Ralf, Arnaldi, Roberta, Keil, Markus, Ketzer, Bernhard Franz, Khabanova, Zhanna, Khan, Ahsan Mehmood, Khan, Shaista, Khanzadeev, Alexei, Kharlov, Yury, Khatun, Anisa, Khuntia, Arvind, Kileng, Bjarte, Arratia Munoz, Miguel Ignacio, Kim, Beomkyu, Kim, Byungchul, Kim, Daehyeok, Kim, Dong Jo, Kim, Eun Joo, Kim, Hyeonjoong, Kim, Jaehyun, Kim, Jinsook, Kim, Jiyoung, Kim, Jungeol, Arsene, Ionut Cristian, Kim, Junlee, Kim, Minjung, Kim, Se Yong, Kim, Taejun, Kim, Taesoo, Kirsch, Stefan, Kisel, Ivan, Kiselev, Sergey, Kisiel, Adam Ryszard, Klay, Jennifer Lynn, Arslandok, Mesut, Klein, Carsten, Klein, Jochen, Klein, Spencer Robert, Klein-boesing, Christian, Kleiner, Matthias, Kluge, Alexander, Knichel, Michael Linus, Knospe, Anders Garritt, Kobdaj, Chinorat, Kohler, Markus Konrad, Augustinus, Andre, Kollegger, Thorsten Sven, Kondratyev, Andrey, Kondratyeva, Natalia, Kondratyuk, Evgeny, Konig, Joshua Leon, Konigstorfer, Stephan Alexander, Konopka, Piotr Jan, Kornakov, Georgui, Koska, Lukas, Kovalenko, Oleksandr, Averbeck, Ralf Peter, Kovalenko, Vladimir, Kowalski, Marek, Kralik, Ivan, Kravcakova, Adela, Kreis, Lukas, Krivda, Marian, Krizek, Filip, Krizkova Gajdosova, Katarina, Kruger, Mario, Kryshen, Evgeny, Aziz, Sizar, Krzewicki, Mikolaj, Kubera, Andrew Michael, Kucera, Vit, Kuhn, Christian Claude, Kuijer, Paulus Gerardus, Kumar, Lokesh, Kundu, Sourav, Kurashvili, Podist, Kurepin, Alexander, Kurepin, Alexey, Aglieri Rinella, Gianluca, Azmi, Mohd Danish, Kuryakin, Alexey, Kushpil, Svetlana, Kvapil, Jakub, Kweon, Min Jung, Kwon, Jiyeon, Kwon, Youngil, La Pointe, Sarah Louise, La Rocca, Paola, Lai, Yue Shi, Lamanna, Massimo, Badala, Angela, Langoy, Rune, Lapidus, Kirill, Lardeux, Antoine Xavier, Larionov, Pavel, Laudi, Elisa, Lavicka, Roman, Lazareva, Tatiana, Lea, Ramona, Leardini, Lucia, Lee, Joonil, Baek, Yongwook, Lee, Seongjoo, Lehner, Sebastian, Lehrbach, Johannes, Lemmon, Roy Crawford, Leon Monzon, Ildefonso, Lesser, Ezra Douglas, Lettrich, Michael, Levai, Peter, Li, Xiaomei, Li, Xing Long, Bagnasco, Stefano, Lien, Jorgen Andre, Lietava, Roman, Lim, Bong-hwi, Lindenstruth, Volker, Lindner, Amelia, Lippmann, Christian, Lisa, Michael Annan, Liu, Alwina Ruixin, Liu, Jian, Liu, Suyuan, Bai, Xiaozhi, Llope, William Joseph, Lofnes, Ingrid Mckibben, Loginov, Vitaly, Loizides, Constantinos, Loncar, Petra, Lopez Lopez, Jorge Andres, Lopez, Xavier Bernard, Lopez Torres, Ernesto, Luhder, Jens Robert, Lunardon, Marcello, Bailhache, Raphaelle Marie, Luparello, Grazia, Ma, Yugang, Maevskaya, Alla, Mager, Magnus, Mahmood, Sohail Musa, Mahmoud, Tariq, Maire, Antonin, Majka, Richard Daniel, Malaev, Mikhail, Malik, Qasim Waheed, Bala, Renu, Malinina, Liudmila, Mal Kevich, Dmitry, Malzacher, Peter, Mandaglio, Giuseppe, Manko, Vladislav, Manso, Franck, Manzari, Vito, Mao, Yaxian, Marchisone, Massimiliano, Mares, Jiri, Balbino, Alessandro, Margagliotti, Giacomo Vito, Margotti, Anselmo, Marin, Ana Maria, Markert, Christina, Marquard, Marco, De Martin, Chiara, Martin, Nicole Alice, Martinengo, Paolo, Martinez, Jacobb Lee, Martinez Hernandez, Mario Ivan, Baldisseri, Alberto, Martinez-garcia, Gines, Masciocchi, Silvia, Masera, Massimo, Masoni, Alberto, Massacrier, Laure Marie, Masson, Erwann, Mastroserio, Annalisa, Mathis, Andreas Michael, Matonoha, Oliver, Toledo Matuoka, Paula Fernanda, Ball, Markus, Matyja, Adam Tomasz, Mayer, Christoph, Mazzaschi, Francesco, Mazzilli, Marianna, Mazzoni, Alessandra Maria, Mechler, Adrian Florin, Meddi, Franco, Melikyan, Yury, Menchaca-rocha, Arturo Alejandro, Cai, Mengke, Agnello, Michelangelo, Balouza, Samah, Meninno, Elisa, Sasikumar Menon, Anjaly, Meres, Michal, Mhlanga, Sibaliso, Miake, Yasuo, Micheletti, Luca, Migliorin, Lucrezia Camilla, Mihaylov, Dimitar Lubomirov, Mikhaylov, Konstantin, Mishra, Aditya Nath, Banerjee, Debjani, Miskowiec, Dariusz Czeslaw, Modak, Abhi, Mohammadi, Naghmeh, Mohanty, Auro Prasad, Mohanty, Bedangadas, Khan, Mohammed Mohisin, Moravcova, Zuzana, Mordasini, Cindy, Moreira De Godoy, Denise Aparecida, Perez Moreno, Luis Alberto, Barbera, Roberto, Morozov, Igor, Morsch, Andreas, Mrnjavac, Teo, Muccifora, Valeria, Mudnic, Eugen, Muhlheim, Daniel Michael, Muhuri, Sanjib, Mulligan, James Declan, Mulliri, Alice, Gameiro Munhoz, Marcelo, Barioglio, Luca, Munzer, Robert Helmut, Murakami, Hikari, Murray, Sean, Musa, Luciano, Musinsky, Jan, Myers, Corey James, Myrcha, Julian Wojciech, Naik, Bharati, Nair, Rahul Ramachandran, Nandi, Basanta Kumar, Barnafoldi, Gergely Gabor, Nania, Rosario, Nappi, Eugenio, Naru, Muhammad Umair, Nassirpour, Adrian Fereydon, Nattrass, Christine, Nayak, Ranjit, Nayak, Tapan Kumar, Nazarenko, Sergey, Neagu, Alexandra, Negrao De Oliveira, Renato Aparecido, Barnby, Lee Stuart, Nellen, Lukas, Nesbo, Simon Voigt, Neskovic, Gvozden, Nesterov, Dmitrii, Neumann, Lukasz Tomasz, Nielsen, Borge Svane, Nikolaev, Sergey, Nikulin, Sergey, Nikulin, Vladimir, Noferini, Francesco, Ramillien Barret, Valerie, Nomokonov, Petr, Norman, Jaime, Novitzky, Norbert, Nowakowski, Piotr, Nyanin, Alexander, Nystrand, Joakim Ingemar, Ogino, Masanori, Ohlson, Alice Elisabeth, Oleniacz, Janusz, Oliveira Da Silva, Antonio Carlos, Bartalini, Paolo, Oliver, Michael Henry, Oppedisano, Chiara, Ortiz Velasquez, Antonio, Oskarsson, Anders Nils Erik, Otwinowski, Jacek Tomasz, Oyama, Ken, Pachmayer, Yvonne Chiara, Pacik, Vojtech, Padhan, Sonali, Pagano, Davide, Bartels, Clara, Paic, Guy, Pan, Jinjin, Panebianco, Stefano, Pareek, Pooja, Park, Jonghan, Parkkila, Jasper Elias, Parmar, Sonia, Pathak, Surya Prakash, Paul, Biswarup, Pazzini, Jacopo, Barth, Klaus, Pei, Hua, Peitzmann, Thomas, Peng, Xinye, Pereira, Luis Gustavo, Pereira Da Costa, Hugo Denis Antonio, Peresunko, Dmitry Yurevich, Mesa Perez, Guillermo, Perrin, Sebastien, Pestov, Yury, Petracek, Vojtech, Agrawal, Neelima, Bartsch, Esther, Petrovici, Mihai, Peretti Pezzi, Rafael, Piano, Stefano, Pikna, Miroslav, Pillot, Philippe, Pinazza, Ombretta, Pinsky, Lawrence, Pinto, Chiara, Pisano, Silvia, Pistone, Daniele, Baruffaldi, Filippo, Ploskon, Mateusz Andrzej, Planinic, Mirko, Pliquett, Fabian, Poghosyan, Martin, Polishchuk, Boris, Poljak, Nikola, Pop, Amalia, Porteboeuf, Sarah Julie, Pozdniakov, Valeriy, Prasad, Sidharth Kumar, Bastid, Nicole, Preghenella, Roberto, Prino, Francesco, Pruneau, Claude Andre, Pshenichnov, Igor, Puccio, Maximiliano, Putschke, Jorn Henning, Qiu, Shi, Quaglia, Luca, Quishpe Quishpe, Raquel Estefania, Ragoni, Simone, Basu, Sumit, Raha, Sibaji, Rajput, Sonia, Rak, Jan, Rakotozafindrabe, Andry Malala, Ramello, Luciano, Rami, Fouad, Rodriguez Ramirez, Saul Anibal, Raniwala, Rashmi, Raniwala, Sudhir, Rasanen, Sami Sakari, Batigne, Guillaume, Rath, Rutuparna, Ratza, Viktor, Ravasenga, Ivan, Read, Kenneth Francis, Redelbach, Andreas Ralph, Redlich, Krzysztof, Rehman, Attiq Ur, Reichelt, Patrick Simon, Reidt, Felix, Ren, Xiaowen, Batyunya, Boris, Renfordt, Rainer Arno Ernst, Jakubcinova, Zuzana, Reygers, Klaus Johannes, Riabov, Andrei, Riabov, Viktor, Richert, Tuva Ora Herenui, Richter, Matthias Rudolph, Riedler, Petra, Riegler, Werner, Riggi, Francesco, Bauri, Dibakar, Ristea, Catalin-lucian, Rode, Sudhir Pandurang, Rodriguez Cahuantzi, Mario, Roeed, Ketil, Rogalev, Roman, Rogochaya, Elena, Rohr, David Michael, Roehrich, Dieter, Fierro Rojas, Pablo, Rokita, Przemyslaw Stefan, Bazo Alba, Jose Luis, Ronchetti, Federico, Rosano, Antonina, Dominguez Rosas, Edgar, Roslon, Krystian, Rossi, Andrea, Rotondi, Alberto, Roy, Ankhi, Roy, Pradip Kumar, Vazquez Rueda, Omar, Rui, Rinaldo, Bearden, Ian Gardner, Rumyantsev, Boris, Rustamov, Anar, Ryabinkin, Evgeny, Ryabov, Yury, Rybicki, Andrzej, Rytkonen, Heidi Maria, Saarimaki, Oskari Antti Matti, Sadek, Rita, Sadhu, Samrangy, Sadovskiy, Sergey, Beattie, Caitlin, Safarik, Karel, Saha, Sumit Kumar, Sahoo, Baidyanath, Sahoo, Pragati, Sahoo, Raghunath, Sahoo, Sarita, Sahu, Pradip Kumar, Saini, Jogender, Sakai, Shingo, Sambyal, Sanjeev Singh, Ahammed, Zubayer, Bedda, Cristina, Samsonov, Vladimir, Sarkar, Debojit, Sarkar, Nachiketa, Sarma, Pranjal, Mantovani Sarti, Valentina, Sas, Mike Henry Petrus, Scapparone, Eugenio, Schambach, Johann Joachim, Scheid, Horst Sebastian, Schiaua, Claudiu Cornel, Behera, Nirbhay Kumar, Schicker, Rainer Martin, Schmah, Alexander, Schmidt, Christian Joachim, Schmidt, Hans Rudolf, Schmidt, Marten Ole, Schmidt, Martin, Schmidt, Nicolas, Schmier, Austin Robert, Schukraft, Jurgen, Schutz, Yves Roland, Belikov, Iouri, Schwarz, Kilian Eberhard, Schweda, Kai Oliver, Scioli, Gilda, Scomparin, Enrico, Seger, Janet Elizabeth, Sekiguchi, Yuko, Sekihata, Daiki, Selyuzhenkov, Ilya, Senyukov, Serhiy, Serebryakov, Dmitry, Bell Hechavarria, Ailec, Sevcenco, Adrian, Shabanov, Arseniy, Shabetai, Alexandre, Shahoyan, Ruben, Shaikh, Wadut, Shangaraev, Artem, Sharma, Anjali, Sharma, Ankita, Sharma, Himanshu, Sharma, Meenakshi, Bellini, Francesca, Sharma, Natasha, Sharma, Sheetal, Sheibani, Oveis, Shigaki, Kenta, Hachiya Shimomura, Maya, Shirinkin, Sergey, Shou, Qiye, Sibiryak, Yury, Siddhanta, Sabyasachi, Siemiarczuk, Teodor, Bellwied, Rene, Silvermyr, David Olle Rickard, Simatovic, Goran, Simonetti, Giuseppe, Singh, Bhawani, Singh, Ranbir, Singh, Randhir, Singh, Ravindra, Singh, Vivek, Singhal, Vikas, Sarkar - Sinha, Tinku, Belyaev, Vladimir, Sitar, Branislav, Sitta, Mario, Skaali, Bernhard, Slupecki, Maciej, Smirnov, Nikolai, Snellings, Raimond, Soncco Meza, Carlos, Song, Jihye, Songmoolnak, Arnon, Soramel, Francesca, Bencedi, Gyula, Sorensen, Soren Pontoppidan, Sputowska, Iwona Anna, Stachel, Johanna, Stan, Ionel, Steffanic, Patrick John, Stenlund, Evert Anders, Stiefelmaier, Stephan Friedrich, Stocco, Diego, Storetvedt, Maksim Melnik, Dello Stritto, Luigi, Beole, Stefania, Alarcon Do Passo Suaide, Alexandre, Sugitate, Toru, Suire, Christophe Pierre, Suleymanov, Mais Kazim Oglu, Suljic, Miljenko, Sultanov, Rishat, Sumbera, Michal, Sumberia, Vikash, Sumowidagdo, Suharyo, Swain, Sagarika, Bercuci, Alexandru, Szabo, Alexander, Szarka, Imrich, Tabassam, Uzma, Taghavi, Seyed Farid, Taillepied, Guillaume, Takahashi, Jun, Tambave, Ganesh Jagannath, Tang, Siyu, Tarhini, Mohamad, Tarzila, Madalina-gabriela, Ahmad, Shakeel, Berdnikov, Yaroslav, Tauro, Arturo, Tejeda Munoz, Guillermo, Telesca, Adriana, Terlizzi, Livia, Terrevoli, Cristina, Thakur, Dhananjaya, Thakur, Sanchari, Thomas, Deepa, Thoresen, Freja, Tieulent, Raphael Noel, Berenyi, Daniel, Tikhonov, Anatoly, Timmins, Anthony Robert, Toia, Alberica, Topilskaya, Nataliya, Toppi, Marco, Torales Acosta, Fernando, Rojas Torres, Solangel, Trifiro, Antonio, Tripathy, Sushanta, Tripathy, Tulika, Bertens, Redmer Alexander, Trogolo, Stefano, Trombetta, Giuseppe, Tropp, Lukas, Trubnikov, Victor, Trzaska, Wladyslaw Henryk, Trzcinski, Tomasz Piotr, Trzeciak, Barbara Antonina, Tumkin, Alexandr, Turrisi, Rosario, Tveter, Trine Spedstad, Berzano, Dario, Ullaland, Kjetil, Umaka, Ejiro Naomi, Uras, Antonio, Usai, Gianluca, Vala, Martin, Valle, Nicolo', Vallero, Sara, Van Der Kolk, Naomi, Van Doremalen, Lennart, Van Leeuwen, Marco, Besoiu, Mihaela Gabriela, Vande Vyvre, Pierre, Varga, Dezso, Varga, Zoltan, Varga-kofarago, Monika, Diozcora Vargas Trevino, Aurora, Vasileiou, Maria, Vasiliev, Andrey, Vazquez Doce, Oton, Vechernin, Vladimir, Vercellin, Ermanno, Betev, Latchezar, Vergara Limon, Sergio, Vermunt, Lucas Anne, Vernet, Renaud, Vertesi, Robert, Vickovic, Linda, Vilakazi, Zabulon, Villalobos Baillie, Orlando, Vino, Gioacchino, Vinogradov, Alexander, Virgili, Tiziano, Bhasin, Anju, Vislavicius, Vytautas, Vodopyanov, Alexander, Volkel, Benedikt, Volkl, Martin Andreas, Voloshin, Kirill, Voloshin, Sergey, Volpe, Giacomo, Von Haller, Barthelemy, Vorobyev, Ivan, Voscek, Dominik, Bhat, Inayat Rasool, Vrlakova, Janka, Wagner, Boris, Weber, Michael, Weber, Steffen Georg, Wegrzynek, Adam Tadeusz, Wenzel, Sandro Christian, Wessels, Johannes Peter, Wiechula, Jens, Wikne, Jon, Wilk, Grzegorz Andrzej, Bhat, Mohammad Asif, Wilkinson, Jeremy John, Willems, Guido Alexander, Willsher, Emily Jade, Windelband, Bernd Stefan, Winn, Michael Andreas, Witt, William Edward, Wright, Josephina Rae, Wu, Yitao, Xu, Ran, Yalcin Kuzu, Serpil, Bhatt, Himani, Yamaguchi, Yorito, Yamakawa, Kosei, Yang, Shiming, Yano, Satoshi, Yin, Zhongbao, Yokoyama, Hiroki, Yoo, In Kwon, Yoon, Jin Hee, Yuan, Shiming, Yuncu, Alperen, Acharya, S., Adamova, D., Adler, A., Adolfsson, J., Aggarwal, M. 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R., Harlenderova, A., Harris, J. W., Harton, A., Hasenbichler, J. A., Hassan, H., Hassan, Q. U., Hatzifotiadou, D., Hauer, P., Havener, L. B., Hayashi, S., Heckel, S. T., Hellbar, E., Helstrup, H., Herghelegiu, A., Herman, T., Hernandez, E. G., Corral, G. H., Herrmann, F., Hetland, K. F., Hillemanns, H., Hills, C., Hippolyte, B., Hohlweger, B., Honermann, J., Horak, D., Hornung, A., Hornung, S., Hosokawa, R., Hristov, P., Huang, C., Hughes, C., Huhn, P., Humanic, T. J., Hushnud, H., Husova, L. A., Hussain, N., Hussain, S. A., Hutter, D., Iddon, J. P., Ilkaev, R., Ilyas, H., Inaba, M., Innocenti, G. M., Ippolitov, M., Isakov, A., Islam, M. S., Ivanov, M., Ivanov, V., Izucheev, V., Jacak, B., Jacazio, N., Jacobs, P. M., Jadlovska, S., Jadlovsky, J., Jaelani, S., Jahnke, C., Jakubowska, M. J., Janik, M. A., Janson, T., Jercic, M., Jevons, O., Jin, M., Jonas, F., Jones, P. G., Jung, J., Jung, M., Jusko, A., Kalinak, P., Kalweit, A., Kaplin, V., Kar, S., Uysal, A. 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N., Uras, A., Usai, G. L., Vala, M., Valle, N., Vallero, S., van der Kolk, N., van Doremalen, L. V. R., van Leeuwen, M., Vyvre, P. V., Varga, D., Varga, Z., Varga-Kofarago, M., Vargas, A., Vasileiou, M., Vasiliev, A., Doce, O. V., Vechernin, V., Vercellin, E., Limon, S. V., Vermunt, L., Vernet, R., Vertesi, R., Vickovic, L., Vilakazi, Z., Baillie, O. V., Vino, G., Vinogradov, A., Virgili, T., Vislavicius, V., Vodopyanov, A., Volkel, B., Volkl, M. A., Voloshin, K., Voloshin, S. A., Volpe, G., von Haller, B., Vorobyev, I., Voscek, D., Vrlakova, J., Wagner, B., Weber, M., Weber, S. G., Wegrzynek, A., Wenzel, S. C., Wessels, J. P., Wiechula, J., Wikne, J., Wilk, G., Wilkinson, J., Willems, G. A., Willsher, E., Windelband, B., Winn, M., Witt, W. E., Wright, J. R., Wu, Y., Xu, R., Yalcin, S., Yamaguchi, Y., Yamakawa, K., Yang, S., Yano, S., Yin, Z., Yokoyama, H., Yoo, I. -K., Yoon, J. H., Yuan, S., Yuncu, A., Yurchenko, V., Zaccolo, V., Zaman, A., Zampolli, C., Zanoli, H. J. C., Zardoshti, N., Zarochentsev, A., Zavada, P., Zaviyalov, N., Zbroszczyk, H., Zhalov, M., Zhang, S., Zhang, X., Zhang, Z., Zherebchevskii, V., Zhi, Y., Zhou, D., Zhou, Y., Zhou, Z., Zhu, J., Zhu, Y., Zichichi, A., Zinovjev, G., Zurlo, N., Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département de Physique Nucléaire (ex SPhN) (DPHN), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de Physique de Clermont (LPC), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Centre de Calcul de l'IN2P3 (CC-IN2P3), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), ALICE, Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), S. 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Pikna, P. Pillot, O. Pinazza, L. Pinsky, C. Pinto, S. Pisano, D. Pistone, M. Płoskoń, M. Planinic, F. Pliquett, M. G. Poghosyan, B. Polichtchouk, N. Poljak, A. Pop, S. Porteboeuf-Houssais, V. Pozdniakov, S. K. Prasad, R. Preghenella, F. Prino, C. A. Pruneau, I. Pshenichnov, M. Puccio, J. Putschke, S. Qiu, L. Quaglia, R. E. Quishpe, S. Ragoni, S. Raha, S. Rajput, J. Rak, A. Rakotozafindrabe, L. Ramello, F. Rami, S. A. R. Ramirez, R. Raniwala, S. Raniwala, S. S. Räsänen, R. Rath, V. Ratza, I. Ravasenga, K. F. Read, A. R. Redelbach, K. Redlich, A. Rehman, P. Reichelt, F. Reidt, X. Ren, R. Renfordt, Z. Rescakova, K. Reygers, A. Riabov, V. Riabov, T. Richert, M. Richter, P. Riedler, W. Riegler, F. Riggi, C. Ristea, S. P. Rode, M. Rodríguez Cahuantzi, K. Røed, R. Rogalev, E. Rogochaya, D. Rohr, D. Röhrich, P. F. Rojas, P. S. Rokita, F. Ronchetti, A. Rosano, E. D. Rosas, K. Roslon, A. Rossi, A. Rotondi, A. Roy, P. Roy, O. V. Rueda, R. Rui, B. Rumyantsev, A. Rustamov, E. Ryabinkin, Y. Ryabov, A. Rybicki, H. Rytkonen, O. A. M. Saarimaki, R. Sadek, S. Sadhu, S. Sadovsky, K. Šafařík, S. K. Saha, B. Sahoo, P. Sahoo, R. Sahoo, S. Sahoo, P. K. Sahu, J. Saini, S. Sakai, S. Sambyal, V. Samsonov, D. Sarkar, N. Sarkar, P. Sarma, V. M. Sarti, M. H. P. Sas, E. Scapparone, J. Schambach, H. S. Scheid, C. Schiaua, R. Schicker, A. Schmah, C. Schmidt, H. R. Schmidt, M. O. Schmidt, M. Schmidt, N. V. Schmidt, A. R. Schmier, J. Schukraft, Y. Schutz, K. Schwarz, K. Schweda, G. Scioli, E. Scomparin, J. E. Seger, Y. Sekiguchi, D. Sekihata, I. Selyuzhenkov, S. Senyukov, D. Serebryakov, A. Sevcenco, A. Shabanov, A. Shabetai, R. Shahoyan, W. Shaikh, A. Shangaraev, A. Sharma, A. Sharma, H. Sharma, M. Sharma, N. Sharma, S. Sharma, O. Sheibani, K. Shigaki, M. Shimomura, S. Shirinkin, Q. Shou, Y. Sibiriak, S. Siddhanta, T. Siemiarczuk, D. Silvermyr, G. Simatovic, G. Simonetti, B. Singh, R. Singh, R. Singh, R. Singh, V. K. Singh, V. Singhal, T. Sinha, B. Sitar, M. Sitta, T. B. Skaali, M. Slupecki, N. Smirnov, R. J. M. Snellings, C. Soncco, J. Song, A. Songmoolnak, F. Soramel, S. Sorensen, I. Sputowska, J. Stachel, I. Stan, P. J. Steffanic, E. Stenlund, S. F. Stiefelmaier, D. Stocco, M. M. Storetvedt, L. D. Stritto, A. A. P. Suaide, T. Sugitate, C. Suire, M. Suleymanov, M. Suljic, R. Sultanov, M. Šumbera, V. Sumberia, S. Sumowidagdo, S. Swain, A. Szabo, I. Szarka, U. Tabassam, S. F. Taghavi, G. Taillepied, J. Takahashi, G. J. Tambave, S. Tang, M. Tarhini, M. G. Tarzila, A. Tauro, G. Tejeda Muñoz, A. Telesca, L. Terlizzi, C. Terrevoli, D. Thakur, S. Thakur, D. Thomas, F. Thoresen, R. Tieulent, A. Tikhonov, A. R. Timmins, A. Toia, N. Topilskaya, M. Toppi, F. Torales-Acosta, S. R. Torres, A. Trifiró, S. Tripathy, T. Tripathy, S. Trogolo, G. Trombetta, L. Tropp, V. Trubnikov, W. H. Trzaska, T. P. Trzcinski, B. A. Trzeciak, A. Tumkin, R. Turrisi, T. S. Tveter, K. Ullaland, E. N. Umaka, A. Uras, G. L. Usai, M. Vala, N. Valle, S. Vallero, N. van der Kolk, L. V. R. van Doremalen, M. van Leeuwen, P. Vande Vyvre, D. Varga, Z. Varga, M. Varga-Kofarago, A. Vargas, M. Vasileiou, A. Vasiliev, O. Vázquez Doce, V. Vechernin, E. Vercellin, S. Vergara Limón, L. Vermunt, R. Vernet, R. Vértesi, L. Vickovic, Z. Vilakazi, O. Villalobos Baillie, G. Vino, A. Vinogradov, T. Virgili, V. Vislavicius, A. Vodopyanov, B. Volkel, M. A. Völkl, K. Voloshin, S. A. Voloshin, G. Volpe, B. von Haller, I. Vorobyev, D. Voscek, J. Vrláková, B. Wagner, M. Weber, S. G. Weber, A. Wegrzynek, S. C. Wenzel, J. P. Wessels, J. Wiechula, J. Wikne, G. Wilk, J. Wilkinson, G. A. Willems, E. Willsher, B. Windelband, M. Winn, W. E. Witt, J. R. Wright, Y. Wu, R. Xu, S. Yalcin, Y. Yamaguchi, K. Yamakawa, S. Yang, S. Yano, Z. Yin, H. Yokoyama, I.-K. Yoo, J. H. Yoon, S. Yuan, A. Yuncu, V. Yurchenko, V. Zaccolo, A. Zaman, C. Zampolli, H. J. C. Zanoli, N. Zardoshti, A. Zarochentsev, P. Závada, N. Zaviyalov, H. Zbroszczyk, M. Zhalov, S. Zhang, X. Zhang, Z. Zhang, V. Zherebchevskii, Y. Zhi, D. Zhou, Y. Zhou, Z. Zhou, J. Zhu, Y. Zhu, A. Zichichi, G. Zinovjev & N. Zurlo, Helsinki Institute of Physics, Sub Subatomic Physics (SAP), Afd Subatomic Physics (SAP), Sub Algemeen Physics Education, and Subatomic Physics

Subjects
EXCHANGE-POTENTIAL APPROACH, Strange quark, ALICE Collaboration, Hadron, Nuclear Theory, Strong interaction, hadron collisions, Position and momentum space, hiukkasfysiikka, nucl-ex, 7. Clean energy, 01 natural sciences, VDP::Fysikk: 430, High Energy Physics - Experiment, High Energy Physics - Experiment (hep-ex), Hadron-Hadron scattering (experiments), scattering [hadron], p p scattering, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], scattering [p p], Nuclear Experiment (nucl-ex), Experimental nuclear physics, NUCLEON, Nuclear Experiment, VDP::Physics: 430, Physics, Multidisciplinary, Large Hadron Collider, strong interaction, lattice [space-time], Publisher Correction, PRIRODNE ZNANOSTI. Fizika, BARYON-BARYON SCATTERING, CERN LHC Coll, LHC, ddc:500, Nucleon, Particle Physics - Experiment, discrete [space-time], Quark, Particle physics, CERN Lab, General Science & Technology, FOS: Physical sciences, short-range, Hadron, strong interaction, LHC, 114 Physical sciences, Fysikk: 430 [VDP], Article, hadron scattering, quark, ultrarelativistic proton–proton collisions, LHC, ALICE, 0103 physical sciences, Nuclear Physics - Experiment, General, 010306 general physics, Physics: 430 [VDP], interaction [hadron hadron], hep-ex, 010308 nuclear & particles physics, High Energy Physics::Phenomenology, effect [strong interaction], hadron-hadron interaction, strong interaction: effect, space-time: discrete, space-time: lattice, correlation, NATURAL SCIENCES. Physics, Baryon, Hypernuclei, Neutron Stars, Strangeness, Physics::Accelerator Physics, High Energy Physics::Experiment, hadron, Experimental particle physics
Abstract

One of the key challenges for nuclear physics today is to understand from first principles the effective interaction between hadrons with different quark content. First successes have been achieved using techniques that solve the dynamics of quarks and gluons on discrete space-time lattices1,2. Experimentally, the dynamics of the strong interaction have been studied by scattering hadrons off each other. Such scattering experiments are difficult or impossible for unstable hadrons3–6 and so high-quality measurements exist only for hadrons containing up and down quarks7. Here we demonstrate that measuring correlations in the momentum space between hadron pairs8–12 produced in ultrarelativistic proton–proton collisions at the CERN Large Hadron Collider (LHC) provides a precise method with which to obtain the missing information on the interaction dynamics between any pair of unstable hadrons. Specifically, we discuss the case of the interaction of baryons containing strange quarks (hyperons). We demonstrate how, using precision measurements of proton–omega baryon correlations, the effect of the strong interaction for this hadron–hadron pair can be studied with precision similar to, and compared with, predictions from lattice calculations13,14. The large number of hyperons identified in proton–proton collisions at the LHC, together with accurate modelling15 of the small (approximately one femtometre) inter-particle distance and exact predictions for the correlation functions, enables a detailed determination of the short-range part of the nucleon-hyperon interaction., Correlations in momentum space between hadrons created by ultrarelativistic proton–proton collisions at the CERN Large Hadron Collider provide insights into the strong interaction, particularly the short-range dynamics of hyperons—baryons that contain strange quarks.

Published
2020

16. Midbrain and Lateral Nucleus Accumbens Dopamine Depletion Affects Free-choice High-fat high-sugar Diet Preference in Male Rats.

Author

Joshi A, Faivre F, la Fleur SE, and Barrot M

Subjects
Animals, Male, Mesencephalon, Oxidopamine toxicity, Rats, Rats, Sprague-Dawley, Sugars, Dopamine, Nucleus Accumbens
Abstract

Dopamine influences food intake behavior. Reciprocally, food intake, especially of palatable dietary items, can modulate dopamine-related brain circuitries. Among these reciprocal impacts, it has been observed that an increased intake of dietary fat results in blunted dopamine signaling and, to compensate this lowered dopamine function, caloric intake may subsequently increase. To determine how dopamine regulates food preference we performed 6-hydroxydopamine (6-OHDA) lesions, depleting dopamine in specific brain regions in male Sprague Dawley rats. Food preference was assessed by providing the rats with free choice access to control diet, fat, 20% sucrose and tap water. Rats with midbrain lesions targeting the substantia nigra (which is also a model of Parkinson's disease) consumed fewer calories, as reflected by a decrease in control diet intake, but they surprisingly displayed an increase in fat intake, without change in the sucrose solution intake compared to sham animals. To determine which of the midbrain dopamine projections may contribute to this effect, we next compared the impact of 6-OHDA lesions of terminal fields, targeting the dorsal striatum, the lateral nucleus accumbens and the medial nucleus accumbens. We found that 6-OHDA lesion of the lateral nucleus accumbens, but not of the dorsal striatum or the medial nucleus accumbens, led to increased fat intake. These findings indicate a role for lateral nucleus accumbens dopamine in regulating food preference, in particular the intake of fat., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Published
2021
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17. Ablation of the tail of the ventral tegmental area compensates symptoms in an experimental model of Parkinson's disease.

Author

Faivre F, Sánchez-Catalán MJ, Dovero S, Bido S, Joshi A, Bezard E, and Barrot M

Subjects
Anhedonia, Animals, Dopamine metabolism, Dopaminergic Neurons metabolism, Male, Models, Theoretical, Neural Pathways metabolism, Oxidopamine pharmacology, Pars Compacta metabolism, Rats, Rats, Sprague-Dawley, Rotarod Performance Test, Substantia Nigra metabolism, Parkinson Disease metabolism, Ventral Tegmental Area metabolism
Abstract

Parkinson's disease is a neurodegenerative disorder partly caused by the loss of the dopamine neurons of the nigrostriatal pathway. It is accompanied by motor as well as non-motor symptoms, including pain and depression. The tail of the ventral tegmental area (tVTA) or rostromedial tegmental nucleus (RMTg) is a GABAergic mesopontine structure that acts as a major inhibitory brake for the substantia nigra pars compacta (SNc) dopamine cells, thus controlling their neuronal activity and related motor functions. The present study tested the influence of suppressing this tVTA brake on motor and non-motor symptoms in a rat model of Parkinson's disease. Using behavioral approaches, we showed that male Sprague-Dawley rats with bilateral and partial 6-hydroxydopamine SNc lesion displayed motor impairments in the rotarod test, impairments that were no more present following a co-lesion of the tVTA. Using a larger set of behavioral tests, we then showed that such SNc lesion also led to non-motor symptoms, including lower body weight, lower mechanical nociceptive thresholds in the forceps test and lower thermal nociceptive thresholds in the incremented hot-plate test, and a decreased sucrose preference in a 2-bottle choice paradigm. The excitotoxic co-lesion of the tVTA led to compensation of body weight, mechanical nociceptive thresholds and anhedonia-like behavior. These findings illustrate the major influence that the tVTA exerts on the dopamine system, modulating the motor and non-motor symptoms related to a partial loss of dopamine cells., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2020
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18. Morphine-dependent and abstinent mice are characterized by a broader distribution of the neurons co-expressing mu and delta opioid receptors.

Author

Pierre F, Ugur M, Faivre F, Doridot S, Veinante P, and Massotte D

Subjects
Analgesics, Opioid adverse effects, Animals, Female, Gene Knock-In Techniques, Hippocampus metabolism, Hyperalgesia drug therapy, Locus Coeruleus metabolism, Male, Mice, Mice, Inbred C57BL, Morphine Dependence drug therapy, Receptor Cross-Talk, Morphine adverse effects, Neurons drug effects, Receptors, Opioid, delta metabolism, Receptors, Opioid, mu metabolism, Substance Withdrawal Syndrome
Abstract

Opiate addiction develops as a chronic relapsing disorder upon drug recreational use or following misuse of analgesic prescription. Mu opioid (MOP) receptors are the primary molecular target of opiates but increasing evidence support in vivo functional heteromerization with the delta opioid (DOP) receptor, which may be part of the neurobiological processes underlying opiate addiction. Here, we used double knock-in mice co-expressing fluorescent versions of the MOP and DOP receptors to examine the impact of chronic morphine administration on the distribution of neurons co-expressing the two receptors. Our data show that MOP/DOP neuronal co-expression is broader in morphine-dependent mice and is detected in novel brain areas located in circuits related to drug reward, motor activity, visceral control and emotional processing underlying withdrawal. After four weeks of abstinence, MOP/DOP neuronal co-expression is still detectable in a large number of these brain areas except in the motor circuit. Importantly, chronic morphine administration increased the proportion of MOP/DOP neurons in the brainstem of morphine-dependent and abstinent mice. These findings establish persistent changes in the abstinent state that may modulate relapse and opiate-induced hyperalgesia and also point to the therapeutic potential of MOP/DOP targeting. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2019
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19. The hidden side of Parkinson's disease: Studying pain, anxiety and depression in animal models.

Author

Faivre F, Joshi A, Bezard E, and Barrot M

Subjects
Animals, Humans, Anxiety physiopathology, Depression physiopathology, Pain physiopathology, Parkinsonian Disorders physiopathology, Parkinsonian Disorders psychology
Abstract

Parkinson's disease is a neurodegenerative disease leading to the loss of midbrain dopamine neurons. It is well known and characterized by motor symptoms that are secondary to the loss of dopamine innervation, but it is also accompanied by a range of various non-motor symptoms, including pain and psychiatric disorders such as anxiety and depression. These non-motor symptoms usually appear at early stages of the disease, sometimes even before the first motor symptoms, and have a dramatic impact on the quality of life of the patients. We review here the present state-of-the-art concerning pain, anxiety and depression-like parameters in animal models of Parkinson's disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2019
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20. Human health risks related to the consumption of foodstuffs of animal origin contaminated by bisphenol A.

Author

Gorecki S, Bemrah N, Roudot AC, Marchioni E, Le Bizec B, Faivre F, Kadawathagedara M, Botton J, and Rivière G

Subjects
Adolescent, Adult, Aged, Animals, Child, Child, Preschool, Consumer Product Safety, Female, Fishes, Food Analysis, Food Contamination statistics & numerical data, France, Humans, Male, Middle Aged, Poultry, Pregnancy, Young Adult, Benzhydryl Compounds analysis, Food Contamination analysis, Meat analysis, Phenols analysis
Abstract

Bisphenol A (BPA) is used in a wide variety of products and objects for consumers use (digital media such as CD's and DVD's, sport equipment, food and beverage containers, medical equipment). For humans, the main route of exposure to BPA is food. Based on previous estimates, almost 20% of the dietary exposure to BPA in the French population would be from food of animal origin. However, due to the use of composite samples, the source of the contamination had not been identified. Therefore, 322 individual samples of non-canned foods of animal origin were collected with the objectives of first updating the estimation of the exposure of the French population and second identifying the source of contamination of these foodstuffs using a specific analytical method. Compared to previous estimates in France, a decline in the contamination of the samples was observed, in particular with regard to meat. The estimated mean dietary exposures ranged from 0.048 to 0.050 μg (kg bw) -1 d -1 for 3-17 year children and adolescents, from 0.034 to 0.035 μg (kg bw) -1 d -1 for adults and from 0.047 to 0.049 μg (kg bw) -1 d -1 for pregnant women. The contribution of meat to total dietary exposure of pregnant women, adults and children was up to three times lower than the previous estimates. Despite this downward trend in contamination, the toxicological values were observed to have been exceeded for the population of pregnant women. With the aim of acquiring more knowledge about the origin the potential source(s) of contamination of non-canned foods of animal origin, a specific analytical method was developed to directly identify and quantify the presence of conjugated BPA (BPA-monoglucuronide, BPA-diglucuronide and sulphate forms) in 50 samples. No conjugated forms of BPAs were detected in the analysed samples, indicating clearly that BPA content in animal food was not due to metabolism but arise post mortem in food. This contamination may occur during food production. However, despite extensive sampling performed in several different shops (butcheries, supermarkets …. ) and in different conditions (fresh, prepared, frozen …), the source(s) of the contamination could not be specifically identified., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2017
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21. Prognostic value of histogram analysis in advanced non-small cell lung cancer: a radiomic study.

Author

Virginia BM, Laura F, Silvia R, Roberto F, Francesco F, Eva H, Charles F, Samy A, Stefan M, Jean-Charles S, Caroline C, and Benjamin B

Abstract

Introduction: Quantitative assessment of heterogeneity by histogram analysis (HA) of tumor images can potentially provide a non-invasive prognostic biomarker. We assessed the prognostic value of HA and evaluated a correlation with molecular signature., Results: CT scans performed between July 2009 and January 2015 from 692 patients were reviewed. HA was performed on scans from 313 patients in the training dataset and 108 in the validation dataset. Median follow-up were 33.7 months [range: 1.7 - 65.5] and 29 months [range: 1.1 - 35.6] with a median overall survival (OS) of 11.7 months [95%CI: 10.7 - 13.1] and 9.5 months [95%CI: 7.9 - 12.7] respectively. Primary mass entropy in coarse texture with spatial filter 3.3 was prognostic for OS in a multivariate Cox analysis (HR: 1.3 [95%CI: 1.1 - 1.5], p =0.001). Results were not reproduced in our validation set and no correlation with molecular signature was identified., Materials and Methods: HA using filtration-histogram method was applied to the region of interest on the primary tumor in enhanced-CT acquired as diagnostic/staging routine, from a cohort of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. The resultants parameters were prospectively applied to a validation dataset. CT scans, clinical and molecular data were retrospectively collected. Cox proportional hazard models were used for survival analysis and Wilcoxon test for correlations., Conclusion: Primary mass entropy was significantly associated with survival in the training set but was not validated in the validation cohort, raising doubt over the reliability of published data from small cohorts., Competing Interests: CONFLICTS OF INTEREST The author declares no conflicts of interest.

Published
2017
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22. Response of the Tail of the Ventral Tegmental Area to Aversive Stimuli.

Author

Sánchez-Catalán MJ, Faivre F, Yalcin I, Muller MA, Massotte D, Majchrzak M, and Barrot M

Subjects
Animals, Antimanic Agents administration & dosage, Antimanic Agents pharmacology, Behavior, Animal drug effects, Carbolines administration & dosage, Carbolines pharmacology, Conditioning, Classical drug effects, Disease Models, Animal, Lipopolysaccharides administration & dosage, Lipopolysaccharides pharmacology, Lithium Chloride pharmacology, Male, Naloxone administration & dosage, Naloxone pharmacology, Narcotic Antagonists administration & dosage, Narcotic Antagonists pharmacology, Neuralgia physiopathology, Neurotoxins administration & dosage, Neurotoxins pharmacology, Olfactory Perception drug effects, Pain chemically induced, Rats, Rats, Sprague-Dawley, Ventral Tegmental Area drug effects, Behavior, Animal physiology, Conditioning, Classical physiology, Morphine Dependence physiopathology, Olfactory Perception physiology, Pain physiopathology, Proto-Oncogene Proteins c-fos drug effects, Receptors, Opioid, mu drug effects, Substance Withdrawal Syndrome physiopathology, Ventral Tegmental Area physiology
Abstract

The GABAergic tail of the ventral tegmental area (tVTA), also named rostromedial tegmental nucleus (RMTg), exerts an inhibitory control on dopamine neurons of the VTA and substantia nigra. The tVTA has been implicated in avoidance behaviors, response to drugs of abuse, reward prediction error, and motor functions. Stimulation of the lateral habenula (LHb) inputs to the tVTA, or of the tVTA itself, induces avoidance behaviors, which suggests a role of the tVTA in processing aversive information. Our aim was to test the impact of aversive stimuli on the molecular recruitment of the tVTA, and the behavioral consequences of tVTA lesions. In rats, we assessed Fos response to lithium chloride (LiCl), β-carboline, naloxone, lipopolysaccharide (LPS), inflammatory pain, neuropathic pain, foot-shock, restraint stress, forced swimming, predator odor, and opiate withdrawal. We also determined the effect of tVTA bilateral ablation on physical signs of opiate withdrawal, and on LPS- and LiCl-induced conditioned taste aversion (CTA). Naloxone-precipitated opiate withdrawal induced Fos in μ-opioid receptor-positive (15%) and -negative (85%) tVTA cells, suggesting the presence of both direct and indirect mechanisms in tVTA recruitment during withdrawal. However, tVTA lesion did not impact physical signs of opiate withdrawal. Fos induction was also present with repeated, but not single, foot-shock delivery. However, such induction was mostly absent with other aversive stimuli. Moreover, tVTA ablation had no impact on CTA. Although stimulation of the tVTA favors avoidance behaviors, present findings suggest that this structure may be important to the response to some, but not all, aversive stimuli.

Published
2017
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23. Radiation dose levels in pediatric chest CT: experience in 499 children evaluated with dual-source single-energy CT.

Author

Martine RJ, Santangelo T, Colas L, Jean-Baptiste F, Duhamel A, Deschildre A, and Remy J

Subjects
Adolescent, Body Weight, Child, Child, Preschool, Female, Humans, Infant, Male, Retrospective Studies, Radiation Dosage, Radiography, Thoracic methods, Tomography, X-Ray Computed methods
Abstract

Background: The availability of dual-source technology has introduced the possibility of scanning children at lower kVp with a high-pitch mode, combining high-speed data acquisition and high temporal resolution., Objective: To establish the radiation dose levels of dual-source, single-energy chest CT examinations in children., Materials and Methods: We retrospectively recorded the dose-length product (DLP) of 499 consecutive examinations obtained in children <50 kg, divided into five weight groups: group 1 (<10 kg, n = 129); group 2 (10-20 kg, n = 176); group 3 (20-30 kg, n = 99), group 4 (30-40 kg, n = 58) and group 5 (40-49 kg, n = 37). All CT examinations were performed with high temporal resolution (75 ms), a high-pitch mode and a weight-adapted selection of the milliamperage., Results: CT examinations were obtained at 80 kVp with a milliamperage ranging between 40 mAs and 90 mAs, and a pitch of 2.0 (n = 162; 32.5%) or 3.0 (n = 337; 67.5%). The mean duration of data acquisition was 522.8 ± 192.0 ms (interquartile range 390 to 610; median 490). In the study population, the mean CT dose index volume (CTDIvol 32 ) was 0.83 mGy (standard deviation [SD] 0.20 mGy; interquartile range 0.72 to 0.94; median 0.78); the mean DLP 32 was 21.4 mGy.cm (SD 9.1 mGy.cm; interquartile range 15 to 25; median 19.0); and the mean size-specific dose estimate (SSDE) was 1.7 mGy (SD 0.4 mGy; interquartile range 1.5 to 1.9; median 1.7). The DLP 32 , CTDI vol32 and SSDE were found to be statistically significant in the five weight categories (P < 0.0001)., Conclusion: This study establishes the radiation dose levels for dual-source, single-kVp chest CT from a single center. In the five weight categories, the median values varied 15-37 mGy.cm for the DLP 32 , 0.78-1.25 mGy for the CTDI vol32 and 1.6-2.1 mGy for the SSDE.

Published
2017
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24. Trends in gastric cancer incidence: a period and birth cohort analysis in a well-defined French population.

Author

Nicolas C, Sylvain M, Come L, Jean F, Anne-Marie B, and Valérie J

Subjects
Adenocarcinoma epidemiology, Adenocarcinoma pathology, Adenocarcinoma, Mucinous epidemiology, Adenocarcinoma, Mucinous pathology, Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Signet Ring Cell epidemiology, Carcinoma, Signet Ring Cell pathology, Child, Child, Preschool, Cohort Studies, Female, France epidemiology, Humans, Infant, Male, Middle Aged, Registries, Young Adult, Stomach Neoplasms epidemiology, Stomach Neoplasms pathology
Abstract

Background: The incidence of gastric cancer has declined over the past decades. Little is known about trends by site and histological subtype. The aim of this study was to analyze changes in gastric cancer incidence patterns in a French well-defined population., Methods: Data on patients with an epithelial gastric cancer diagnosed between 1982 and 2011 were collected by the population-based digestive cancer registry of Burgundy (n = 4694). Time trends in gastric cancer incidence by period of diagnosis and birth cohort were analyzed by sex, subsite, and histological type., Results: There was a decrease in incidence rates for antral carcinomas (-2.6 % per year in males, -2.5 % per year in females; p < 0.001) and corpus carcinomas (-3.3 % and -3.2 %, respectively; p < 0.001). Annual percentage changes were not significant for fundus carcinomas in both sexes and cardia carcinoma in females, although they increased in males (+1.0 % per year; p < 0.02).When comparing the 1900 cohort and the 1950 cohort, there was a five- to sevenfold decrease in the cumulative risk at 0-79 years for corpus and antral carcinomas in both sexes and a threefold decrease for fundus carcinomas. There were minor variations for cardia carcinomas. There was a decrease of incidence both by period of diagnosis and by birth cohort for adenocarcinoma and colloid carcinoma. It was more marked for undifferentiated carcinoma. The variation for signet-ring carcinoma was minor., Conclusion: Temporal variations in incidence rates of gastric cancer differed according to subsite and histology, suggesting different etiological factors. Available analytical studies provide an explanation for the reported trends by subsite.

Published
2016
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25. [Palliative care practices in residential facilities for the elderly requiring full-time care].

Author

Degois M, Grillot A, Boyraci E, Saillard V, Jandard AC, Prévalet-Courlet L, Ngamba E, Faivre F, Barrandon O, and Aubry R

Subjects
Aged, 80 and over, Female, France, Homes for the Aged standards, Humans, Male, Nursing Homes standards, Pain Management standards, Palliative Care standards, Peer Review, Quality Improvement, Retrospective Studies, Terminal Care methods, Terminal Care standards, Homes for the Aged statistics & numerical data, Nursing Homes statistics & numerical data, Pain Management methods, Palliative Care methods
Abstract

Aims: The purpose of this study was to assess palliative care practices for residents of Larmont residential facilities for the elderly requiring full-time care (Doubs, France) throughout their stay., Methods: This was a healthcare peer review based on a retrospective clinical audit in compliance with the recommendations of the French Health Authority. The 252-bed Larmont residential care facilities for the elderly is a public institution, attached to the local Hospital. The 72 residents of the Larmont residential care facilities for the elderly who died during 2012 were included in the study., Results: Death occurred on the premises for 95.8 percent of residents. The proposal to appoint a support person was recorded in 27.6 percent of audited cases. End-of-life instructions were recorded in 23.2 percent of cases. In 31.8 percent of cases, the medical record referred to a multidisciplinary procedure, which complied with regulations in less than one half of cases. The residents’ pain at the end of their life was insufficiently assessed and managed. A discomfort other than pain was identified in 89.2 percent of cases., Conclusions: This healthcare peer review led to a quality improvement plan focusing on three areas : ensure that medical practices are in line with patients’ rights, anticipate identification of the end of life and improve management of pain and suffering at the end of life.

Published
2015

26. Quality control of extracorporeal photochemotherapy: Proliferation assay using CFSE validated according to ISO 15189:2007 standards.

Author

Lionel F, Lucie L, Wang-Qing L, Isabelle K, Camille L, Michel V, Sabine L, Jean-Louis B, Philippe B, Hélène R, and Brigitte B

Abstract

Background: For the last 40 years, the technique of extracorporeal photopheresis has constantly developed. Among irradiation systems, those called 'off-line' allow the validation of the quality of the cell therapy product. The inhibition of the proliferation of lymphocytes after UVA irradiation is usually verified by the tritiated thymidine assay as in vitro proliferation assay. The document presented here describes the results obtained while performing the setting up of an alternative proliferation assay using flow cytometry according to ISO 15189:2007 Standard. Methods: Cells samples taken before and after UVA irradiation were labeled with CFSE and then cultured with phytohemagglutinin. After 3 days, an analysis of the CFSE staining was realized by flow cytometry. In order to validate the shift in the method used according to Standard, the following tests were performed: 1) comparison with the reference method, 2) robustness test, 3) reagents stability. Results: Comparison method demonstrated that the sensitivity of the CFSE test is 100%, the specificity is 89% and the concordance is almost complete. The CFSE test is robust regarding parameters like cell concentration or PHA concentration. PHA and CFSE are stable for 6 months and one year, respectively. Conclusion: Validation of this alternative test, according to the ISO 15189:2007 Standard, has demonstrated good concordance with reference method. The results of the robustness and stability of reagents are appropriate for its routine use. Thus, the benefits of alternative technique make it a wise choice for the quality control of ECP in a cell therapy laboratory. © 2014 Clinical Cytometry Society., (Copyright © 2014 Clinical Cytometry Society.)

Published
2014
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27. Vectorization efforts to increase Gram-negative intracellular drug concentration: a case study on HldE-K inhibitors.

Author

Atamanyuk D, Faivre F, Oxoby M, Ledoussal B, Drocourt E, Moreau F, and Gerusz V

Subjects
Aminoglycosides pharmacology, Anti-Bacterial Agents metabolism, Erythromycin chemistry, Erythromycin pharmacology, Escherichia coli drug effects, Lipopolysaccharides biosynthesis, Microbial Sensitivity Tests, Multienzyme Complexes drug effects, Nucleotidyltransferases drug effects, Phosphotransferases (Alcohol Group Acceptor) drug effects, Polyamines pharmacology, Polyelectrolytes, Erythromycin metabolism, Escherichia coli metabolism, Multienzyme Complexes antagonists & inhibitors, Nucleotidyltransferases antagonists & inhibitors, Phosphotransferases (Alcohol Group Acceptor) antagonists & inhibitors
Abstract

In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.

Published
2013
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28. Novel HldE-K inhibitors leading to attenuated Gram negative bacterial virulence.

Author

Desroy N, Denis A, Oliveira C, Atamanyuk D, Briet S, Faivre F, LeFralliec G, Bonvin Y, Oxoby M, Escaich S, Floquet S, Drocourt E, Vongsouthi V, Durant L, Moreau F, Verhey TB, Lee TW, Junop MS, and Gerusz V

Subjects
Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Benzothiazoles chemistry, Benzothiazoles pharmacology, Escherichia coli pathogenicity, Lipopolysaccharides pharmacology, Microbial Sensitivity Tests, Structure-Activity Relationship, Triazines chemistry, Triazines pharmacology, Virulence drug effects, Anti-Bacterial Agents chemical synthesis, Benzothiazoles chemical synthesis, Escherichia coli drug effects, Multienzyme Complexes antagonists & inhibitors, Nucleotidyltransferases antagonists & inhibitors, Phosphotransferases (Alcohol Group Acceptor) antagonists & inhibitors, Triazines chemical synthesis
Abstract

We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains. One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pump deleted E. coli strains. This compound did not interfere with E. coli bacterial growth (MIC > 32 μg/mL) but sensitized this pathogen to hydrophobic antibiotics like macrolides normally inactive on Gram-negative bacteria. In addition, 86 could sensitize E. coli to serum complement killing. These results demonstrate that HldE kinase is a suitable target for drug discovery. They also pave the way toward novel possibilities of treating or preventing bloodstream infections caused by pathogenic Gram negative bacteria by inhibiting specific virulence factors.

Published
2013
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29. From triclosan toward the clinic: discovery of nonbiocidal, potent FabI inhibitors for the treatment of resistant bacteria.

Author

Gerusz V, Denis A, Faivre F, Bonvin Y, Oxoby M, Briet S, LeFralliec G, Oliveira C, Desroy N, Raymond C, Peltier L, Moreau F, Escaich S, Vongsouthi V, Floquet S, Drocourt E, Walton A, Prouvensier L, Saccomani M, Durant L, Genevard JM, Sam-Sambo V, and Soulama-Mouze C

Subjects
Animals, Anti-Infective Agents, Local chemical synthesis, Benzamides chemical synthesis, Cells, Cultured, Dogs, Drug Evaluation, Preclinical, Humans, Microbial Sensitivity Tests, Models, Molecular, Molecular Structure, Phenyl Ethers chemical synthesis, Rats, Structure-Activity Relationship, Triclosan chemical synthesis, Anti-Infective Agents, Local pharmacology, Benzamides pharmacology, Drug Resistance, Multiple, Bacterial drug effects, Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) antagonists & inhibitors, Gram-Negative Bacteria drug effects, Phenyl Ethers pharmacology, Triclosan pharmacology
Abstract

In this paper, we present some elements of our optimization program to decouple triclosan's specific FabI effect from its nonspecific cytotoxic component. The implementation of this strategy delivered highly specific, potent, and nonbiocidal new FabI inhibitors. We also disclose some preclinical data of one of their representatives, 83, a novel antibacterial compound active against resistant staphylococci and some clinically relevant Gram negative bacteria that is currently undergoing clinical trials.

Published
2012
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30. GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype.

Author

Paznekas WA, Karczeski B, Vermeer S, Lowry RB, Delatycki M, Laurence F, Koivisto PA, Van Maldergem L, Boyadjiev SA, Bodurtha JN, and Jabs EW

Subjects
Amino Acid Sequence, Connexin 43 chemistry, Connexin 43 genetics, Humans, Molecular Sequence Data, Phenotype, Polymorphism, Genetic, Abnormalities, Multiple genetics, Mutation genetics
Abstract

The predominantly autosomal dominant disorder, oculodentodigital dysplasia (ODDD) has high penetrance with intra- and interfamilial phenotypic variability. Abnormalities observed in ODDD affect the eye, dentition, and digits of the hands and feet. Patients present with a characteristic facial appearance, narrow nose, and hypoplastic alae nasi. Neurological problems, including dysarthria, neurogenic bladder disturbances, spastic paraparesis, ataxia, anterior tibial muscle weakness, and seizures, are known to occur as well as conductive hearing loss, cardiac defects, and anomalies of the skin, hair, and nails. In 2003, our analysis of 17 ODDD families revealed that each had a different mutation within the human gap junction alpha 1 (GJA1) gene which encodes the protein connexin 43 (Cx43). Since then at least 17 publications have identified an additional 26 GJA1 mutations and in this study, we present 28 new cases with 18 novel GJA1 mutations. We include tables summarizing the 62 known GJA1 nucleotide changes leading to Cx43 protein alterations and the phenotypic information available on 177 affected individuals from 54 genotyped families. Mutations resulting in ODDD occur in each of the nine domains of the Cx43 protein, and we review our functional experiments and those in the literature, examining the effects of 13 different Cx43 mutations upon gap junction activity., (Copyright 2009 Wiley-Liss, Inc.)

Published
2009
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