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Year of publication
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- LHC (7)
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- ALICE experiment (3)
- Hadron-Hadron Scattering (3)
- pp collisions (3)
- Beauty production (2)
- Single electrons (2)
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Rapidity and transverse momentum dependence of inclusive J/ψ production in pp collisions at √s=7 TeV
(2011)
Aamodt, Kenneth ; Abrahantes Quintana, A. ; Adamová, Dagmar ; Adare, A.M. ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agocs, A.G. ; Agostinelli, A. ; Aguilar Salazar, S. ; Ahammed, Zubayer ; Ahmad, Nazeer ; Ahmad Masoodi, A. ; Ahn, Sang Un ; Akindinov, Alexander ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Almaráz Aviña, E. ; Alme, Johan ; Alt, Torsten ; Altini, V. ; Altsybeev, Igor ; Andrei, Cristian ; Andronic, Anton ; Anguelov, Venelin ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arbor, N. ; Arcelli, Silvia ; Arend, A. ; Armesto, Néstor ; Arnaldi, Roberta ; Aronsson, Tomas Robert ; Arsene, Ionut Cristian ; Asryan, A. ; Augustinus, Andre ; Averbeck, Ralf Peter ; Awes, T.C. ; Äystö, J. ; Azmi, Mohd Danish ; Bach, Matthias ; Badalà, Angela ; Baek, Yong Wook ; Bailhache, Raphaëlle ; Bala, Remu ; Baldini Ferroli, Rinaldo ; Baldisseri, Alberto ; 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The ALICE experiment at the LHC has studied inclusive J/ψ production at central and forward rapidities in pp collisions at √s=7 TeV. In this Letter, we report on the first results obtained detecting the J/ψ through the dilepton decay into e+e− and μ+μ− pairs in the rapidity ranges |y|<0.9 and 2.5<y<4, respectively, and with acceptance down to zero pT. In the dielectron channel the analysis was carried out on a data sample corresponding to an integrated luminosity Lint=5.6 nb−1 and the number of signal events is NJ/ψ=352±32(stat.)±28(syst.); the corresponding figures in the dimuon channel are Lint=15.6 nb−1 and NJ/ψ=1924±77(stat.)±144(syst.). The measured production cross sections are σJ/ψ(|y|<0.9)=10.7±1.0(stat.)±1.6(syst.)−2.3+1.6(syst.pol.)μb and σJ/ψ(2.5<y<4)=6.31±0.25(stat.)±0.76(syst.)−1.96+0.95(syst.pol.)μb. The differential cross sections, in transverse momentum and rapidity, of the J/ψ were also measured.
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Heavy flavour decay muon production at forward rapidity in proton–proton collisions at √s=7 TeV
(2012)
Abelev, Betty ; Adam, Jaroslav ; Adamová, Dagmar ; Adare, A.M. ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agocs, A.G. ; Agostinelli, A. ; Aguilar Salazar, S. ; Ahammed, Zubayer ; Ahmad, Nazeer ; Ahmad Masoodi, A. ; Ahn, Sang Un ; Akindinov, Alexander ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Almaráz Aviña, E. ; Alt, Torsten ; Altini, V. ; Altinpinar, Sedat ; Altsybeev, Igor ; Andrei, Cristian ; Andronic, Anton ; Anguelov, Venelin ; Anielski, Jonas ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arbor, N. ; Arcelli, Silvia ; Arend, A. ; Armesto, Néstor ; Arnaldi, Roberta ; Aronsson, Tomas Robert ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Asryan, A. ; Augustinus, Andre ; Averbeck, Ralf Peter ; Awes, T.C. ; Äystö, J. ; Azmi, Mohd Danish ; Bach, Matthias ; Badalà, Angela ; Baek, Yong Wook ; Bailhache, Raphaëlle ; Bala, Remu ; 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Morando, Maurizio ; Godoy, Denise Aparecida Moreira de ; Moretto, Sandra ; Morsch, Andreas ; Muccifora, Valeria ; Mudnic, Eugen ; Muhuri, Sanjib ; Müller, H. ; Munhoz, Marcelo Gameiro ; Musa, Luciano ; Musso, A. ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Nattrass, Christine ; Naumov, N.P. ; Navin, S. ; Nayak, Tapan Kumar ; Nazarenko, Sergey ; Nazarov, G. ; Nedosekin, Alexander ; Nicassio, Maria ; Nielsen, Borge Svane ; Niida, Takafumi ; Nikolaev, Sergey ; Nikolic, V. ; Nikulin, Vladimir ; Nikulin, Sergey ; Nilsen, B.S. ; Nilsson, M.S. ; Noferini, Francesco ; Nomokonov, Petr V. ; Nooren, Gerardus ; Novitzky, Norbert ; Nyanin, Alexander ; Nyatha, A. ; Nygaard, C. ; Nystrand, Joakim Ingemar ; Ochirov, A. ; Oeschler, Helmut ; Oh, Saehanseul ; Oh, Sun Kun ; Oleniacz, Janusz ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Ortona, G. ; Oskarsson, Anders Nils Erik ; Ostrowski, P. ; Otterlund, I. ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Ozawa, K. ; Pachmayer, Yvonne C. ; Pachr, Miloš ; Padilla, F. ; Pagano, Paola ; Paić, Guy ; Painke, F. ; Pajares Vales, Carlos ; Pal, S. ; Pal, Susanta Kumar ; Palaha, A. ; Palmeri, A. ; Papikyan, Vardanush ; Pappalardo, Giuseppe Salvatore ; Park, WooJin ; Passfeld, Annika ; Pastirčák, B. ; Patalakha, D.I. ; Paticchio, Vincenzo ; Pavlinov, A. ; Pawlak, Tomasz Jan ; Peitzmann, Thomas ; Perales, M. ; Filho, Elienos Pereira de Oliveira ; Peresunko, Dmitry Yurevich ; Pérez Lara, Carlos Eugenio ; Pérez Lezama, Edgar ; Perini, D. ; Perrino, D. ; Peryt, Wiktor Stanislaw ; Pesci, A. ; Peskov, Vladimir ; Pestov, Yury N. ; Petráček, Vojtech ; Petran, M. ; Petris, M. ; Petrov, P. ; Petrovici, Mihai A. ; Petta, Catia ; Piano, Stefano ; Piccotti, A. ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pitz, N. ; Piuz, F. ; Piyarathna, Danthasinghe B. ; Płoskoń, Mateusz ; Pluta, Jan Marian ; Pocheptsov, T. ; Pochybova, Sona ; Podesta Lerma, Pedro Luis Manuel ; Poghosyan, Martin G. ; Polák, K. ; Polichtchouk, Boris ; Pop, Amalia ; Porteboeuf-Houssais, Sarah Julie ; Pospíšil, V. ; Potukuchi, B. ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puchagin, S. ; Puddu, Giovanna ; Pulvirenti, A. ; Punin, Valery ; Putiš, M. ; Putschke, Jörn H. ; Quercigh, E. ; Qvigstad, Henrik ; Rachevski, Alexandre ; Rademakers, A. ; Radomski, S. ; Räihä, T.S. ; Rak, Jan ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Ramírez Reyes, A. ; Raniwala, Rashmi ; Raniwala, Sudhir ; Räsänen, Sami Sakari ; Rascanu, Bogdan Theodor ; Rathee, Deepika ; Read, Kenneth Francis ; Real, Jean-Sébastien ; Redlich, Krzysztof ; Reichelt, Patrick ; Reicher, Martijn ; Renfordt, Rainer Arno Ernst ; Reolon, Anna Rita ; Reshetin, Andrey ; Rettig, Felix Vincenz ; Revol, Jean-Pierre ; Reygers, Klaus ; Riccati, L. ; Ricci, Renato Angelo ; Richert, Tuva Ora Herenui ; Richter, Matthias ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Rodrı́guez Cahuantzi, Mario ; Røed, Ketil ; Rohr, David ; Röhrich, Dieter ; Romita, Rosa ; Ronchetti, Federico ; Rosnet, Philippe ; Rossegger, S. ; Rossi, Andrea ; Roukoutakis, Filimon ; Roy, Pradip Kumar ; Roy, Christelle Sophie ; Rubio Montero, Antonio Juan ; Rui, Rinaldo ; Ryabinkin, Evgeny ; Rybicki, Andrzej ; Sadovskiy, Sergey ; Šafařík, Karel ; Sahu, Pradip Kumar ; Saini, Jogender ; Sakaguchi, H. ; Sakai, Shingo ; Sakata, D. ; Salgado, Carlos A. ; Salzwedel, Jai ; Sambyal, Sanjeev Singh ; Samsonov, Vladimir ; Sanchez Castro, Xitzel ; Šándor, Ladislav ; Sandoval, Andres ; Sano, S. ; Sano, Masato ; Santo, R. ; Santoro, R. ; Sarkamo, J. ; Scapparone, Eugenio ; Scarlassara, Fernando ; Scharenberg, Rolf Paul ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schmidt, Hans Rudolf ; Schmidt, Christian Joachim ; Schreiner, S. ; Schuchmann, Simone ; Schukraft, Jürgen ; Schutz, Yves Roland ; Schwarz, Kilian ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Scott, Rebecca Michelle ; Scott, P.A. ; Segato, G. ; Selyuzhenkov, Ilya ; Senyukov, Serhiy ; Seo, Jeewon ; Serci, S. ; Serradilla, Eulogio ; Sevcenco, Adrian ; Sgura, I. ; Shabetai, Alexandre ; Shabratova, G. ; Shahoyan, Ruben ; Sharma, S. ; Sharma, Natasha ; Shigaki, Kenta ; Shimomura, Maya ; Shtejer, Katherin ; Sibiriak, Yury ; Siciliano, M. ; Sicking, E. ; Siddhanta, Sabyasachi ; Siemiarczuk, Teodor ; Silvermyr, David Olle Rickard ; Simonetti, Giuseppe ; Singaraju, Rama Narayana ; Singh, R. ; Singha, Subhash ; Sarkar-Sinha, Tinku ; Sinha, Bikash ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Skjerdal, K. ; Smakal, R. ; Smirnov, Nikolai ; Snellings, Raimond ; Søgaard, C. ; Soltz, Ron ; Son, H. ; Song, J. ; Song, M. ; Soos, C. ; Soramel, Francesca ; Sputowska, Iwona Anna ; Spyropoulou-Stassinaki, Martha ; Srivastava, Brijesh Kumar ; Stachel, Johanna ; Stan, Ionel ; Stan, Ionel ; Stefanek, Grzegorz ; Stefanini, G. ; Steinbeck, T. ; Steinpreis, M. ; Stenlund, Evert Anders ; Steyn, Gideon Francois ; Stocco, Diego ; Stolpovskiy, M. ; Strabykin, K. ; Strmen, Peter ; Suaide, Alexandre Alarcon do Passo ; Subieta Vasquez, Martin Alfonso ; Sugitate, Toru ; Suire, Christophe Pierre ; Sukhorukov, M. ; Sultanov, Rishat ; Šumbera, Michal ; Šuša, Tatjana ; Toledo, Alejandro Szanto de ; Szarka, Imrich ; Szostak, A. ; Tagridis, C. ; Takahashi, Jun ; Tapia Takaki, Jesus Daniel ; Tauro, Arturo ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terrevoli, Cristina ; Thäder, Jochen ; Thomas, Deepa ; Thomas, James H. ; Tieulent, Raphael Noel ; Timmins, Anthony Robert ; Tlusty, David ; Toia, Alberica ; Torii, H. ; Toscano, L. ; Tosello, F. ; Traczyk, T. ; Truesdale, David Christopher ; Trzaska, Wladyslaw Henryk ; Tsuji, Tomoya ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ulery, Jason Glyndwr ; Ullaland, Kjetil ; Ulrich, Jiri ; Uras, Antonio ; Urbán, J. ; Urciuoli, G.M. ; Usai, Gianluca ; Vajzer, Michal ; Vala, Martin ; Valencia Palomo, Lizardo ; Vallero, Sara ; Kolk, Naomi van der ; Vyvre, Pierre vande ; Leeuwen, Marco van ; Vannucci, L. ; Vargas Treviño, Maria Aurora Diozcora ; Varma, Raghava ; Vasileiou, Maria ; Vasiliev, Andrey ; Vechernin, Vladimir ; Veldhoen, Misha ; Venaruzzo, Massimo ; Vercellin, Ermanno ; Vergara, S. ; Vernekohl, D.C. ; Vernet, Renaud ; Verweij, Marta ; Vicković, Linda ; Viesti, Giuseppe ; Vikhlyantsev, O. ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Vinogradov, Leonid ; Vinogradov, Alexander A. ; Vinogradov, Yury I. ; Virgili, Tiziano ; Viyogi, Yogendra P. ; Vodopyanov, Alexander ; Voloshin, Sergei ; Voloshin, Kirill ; Volpe, Giacomo ; Haller, Barthélémy von ; Vranić, Danilo ; Øvrebekk, G. ; Vrláková, Janka ; Vulpescu, Bogdan ; Vyushin, Alexey ; Wagner, V. ; Wagner, Boris ; Wan, R. ; Wang, Y. ; Wang, D. ; Wang, Y. ; Wang, M. ; Watanabe, K. ; Wessels, Johannes P. ; Westerhoff, Uwe ; Wiechula, Jens ; Wikne, Jon ; Wilde, Martin ; Wilk, Grzegorz Andrzej ; Wilk, A. ; Williams, M. Crispin S. ; Windelband, Bernd ; Xaplanteris Karampatsos, L. ; Yang, H. ; Yang, S. ; Yasnopolskiy, S. ; Yi, J. ; Yin, Zhongbao ; Yokoyama, Hiroki ; Yoo, In-Kwon ; Yoon, J. ; Yu, W. ; Yuan, X. ; Yushmanov, Igor E. ; Zach, C. ; Zampolli, Chiara ; Zaporozhets, Sergey ; Zarochentsev, Andrey ; Závada, Petr ; Zaviyalov, Nikolaj ; Zbroszczyk, Hanna Paulina ; Zelnicek, P. ; Zgura, Ion-Sorin ; Zhalov, Mikhail ; Zhang, X. ; Zhou, Y. ; Zhou, D. ; Zhou, F. ; Zhu, X. ; Zichichi, Antonino ; Zimmermann, Alice ; Zinovjev, Gennady M. ; Zoccarato, Y. ; Zynovyev, M.
The production of muons from heavy flavour decays is measured at forward rapidity in proton–proton collisions at √s=7 TeV collected with the ALICE experiment at the LHC. The analysis is carried out on a data sample corresponding to an integrated luminosity Lint=16.5 nb−1. The transverse momentum and rapidity differential production cross sections of muons from heavy flavour decays are measured in the rapidity range 2.5<y<4, over the transverse momentum range 2<pt<12 GeV/c. The results are compared to predictions based on perturbative QCD calculations.
Medema, Marnix H. ; Kottmann, Renzo ; Yilmaz, Pelin ; Cummings, Matthew ; Biggins, John B. ; Kai, Blin ; de Bruijn, Irene ; Chooi, Yit Heng ; Claesen, Jan ; Coates, R. Cameron ; Cruz-Morales, Pablo ; Duddela, Srikanth ; Düsterhus, Stephanie ; Edwards, Daniel J. ; Fewer, David P. ; Garg, Neha ; Geiger, Christoph ; Gomez-Escribano, Juan Pablo ; Greule, Anja ; Hadjithomas, Michalis ; Haines, Anthony S. ; Helfrich, Eric J. N. ; Hillwig, Matthew L. ; Ishida, Keishi ; Jones, Adam C. ; Jones, Carla S. ; Jungmann, Katrin ; Kegler, Carsten ; Kim, Hyun Uk ; Kötter, Peter ; Krug, Daniel ; Masschelein, Joleen ; Melnik, Alexey V. ; Mantovan, Simone M. ; Monroe, Emily A. ; Moore, Marcus ; Moss, Nathan ; Nützmann, Hans-Wilhelm ; Pan, Guohui ; Pati, Amrita ; Petras, Daniel ; Reen, F. Jerry ; Rosconi, Federico ; Rui, Zhe ; Tian, Zhenhua ; Tobias, Nicholas J. ; Tsunematsu, Yuta ; Wiemann, Philipp ; Wyckoff, Elizabeth ; Yan, Xiaohui ; Yim, Grace ; Yu, Fengan ; Xie, Yunchang ; Aigle, Bertrand ; Apel, Alexander K. ; Balibar, Carl J. ; Balskus, Emily P. ; Barona-Gómez, Francisco ; Bechthold, Andreas ; Bode, Helge Björn ; Borriss, Rainer ; Brady, Sean F. ; Brakhage, Axel A. ; Caffrey, Patrick ; Cheng, Yi-Qiang ; Clardy, Jon ; Cox, Russell J. ; De Mot, René ; Donadio, Stefano ; Donia, Mohamed S. ; van der Donk, Wilfred A. ; Dorrestein, Pieter C. ; Doyle, Sean ; Driessen, Arnold J. M. ; Ehling-Schulz, Monika ; Entian, Karl-Dieter ; Fischbach, Michael A. ; Gerwick, Lena ; Gerwick, William H. ; Gross, Harald ; Gust, Bertolt ; Hertweck, Christian ; Höfte, Monica ; Jensen, Susan E. ; Ju, Jianhua ; Katz, Leonard ; Kaysser, Leonard ; Klassen, Jonathan L. ; Keller, Nancy P. ; Kormanec, Jan ; Kuipers, Oscar P. ; Kuzuyama, Tomohisa ; Kyrpides, Nikos C. ; Kwon, Hyung-Jin ; Lautru, Sylvie ; Lavigne, Rob ; Lee, Chia Y. ; Linquan, Bai ; Liu, Xinyu ; Liu, Wen ; Luzhetskyy, Andriy ; Mahmud, Taifo ; Mast, Yvonne ; Méndez, Carmen ; Metsä-Ketelä, Mikko ; Micklefield, Jason ; Mitchell, Douglas A. ; Moore, Bradley S. ; Moreira, Leonilde M. ; Müller, Rolf ; Neilan, Brett A. ; Nett, Markus ; Nielsen, Jens ; O’Gara, Fergal ; Oikawa, Hideaki ; Osbourn, Anne ; Osburne, Marcia S. ; Ostash, Bohdan ; Payne, Shelley M. ; Pernodet, Jean-Luc ; Petricek, Miroslav ; Piel, Jörn ; Ploux, Olivier ; Raaijmakers, Jos M. ; Salas, José A. ; Schmitt, Esther K. ; Scott, Barry ; Seipke, Ryan F. ; Shen, Ben ; Sherman, David H. ; Sivonen, Kaarina ; Smanski, Michael J. ; Sosio, Margherita ; Stegmann, Evi ; Süssmuth, Roderich D. ; Tahlan, Kapil ; Thomas, Christopher M. ; Tang, Yi ; Truman, Andrew W. ; Viaud, Muriel ; Walton, Jonathan D. ; Walsh, Christopher T. ; Weber, Tilmann ; van Wezel, Gilles P. ; Wilkinson, Barrie ; Willey, Joanne M. ; Wohlleben, Wolfgang ; Wright, Gerard D. ; Ziemert, Nadine ; Zhang, Changsheng ; Zotchev, Sergey B. ; Breitling, Rainer ; Takano, Eriko ; Glöckner, Frank Oliver
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Proneth, Andrea ; Schnitzbauer, Andreas ; Zeman, Florian ; Foerster, Johanna R. ; Holub, Ines ; Arbogast, Helmut ; Bechstein, Wolf Otto ; Becker, Thomas ; Dietz, Carsten ; Guba, Markus ; Heise, Michael ; Jonas, Sven ; Kersting, Stephan ; Klempnauer, Jürgen ; Manekeller, Steffen ; Müller, Volker ; Nadalin, Silvio ; Nashan, Björn ; Pascher, Andreas ; Rauchfuss, Falk ; Ströhlein, Michael A. ; Schemmer, Peter ; Schenker, Peter ; Thorban, Stefan ; Vogel, Thomas ; Rahmel, Axel ; Viebahn, Richard ; Banas, Bernhard ; Geissler, Edward K. ; Schlitt, Hans J. ; Farkas, Stefan A.
Background: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients.
Methods/Design: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation.
Discussion: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.
Trial registered at: NCT01384006
Lange, Christian ; Bibert, Stephanie ; Kutalik, Zoltán ; Burgisser, Philippe ; Cerny, Andreas ; Dufour, Jean-Francois ; Geier, Andreas ; Gerlach, Tilman J. ; Heim, Markus H. ; Malinverni, Raffaele ; Negro, Francesco ; Regenass, Stephan ; Badenhoop, Klaus ; Bojunga, Jörg ; Sarrazin, Christoph ; Zeuzem, Stefan ; Müller, Tobias ; Berg, Thomas ; Bochud, Pierre-Yves ; Moradpour, Darius
Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.
Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome.
Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome.
Miethke, Marcus ; Pieroni, Marco ; Weber, Karl Tilmann ; Brönstrup, Mark ; Hammann, Peter ; Halby, Ludovic ; Arimondo, Paola B. ; Glaser, Philippe ; Aigle, Bertrand ; Bode, Helge Björn ; Moreira, Rui ; Li, Yanyan ; Luzhetskyy, Andriy ; Medema, Marnix H. ; Pernodet, Jean-Luc ; Stadler, Marc ; Tormo, José Rubén ; Genilloud, Olga ; Truman, Andrew W. ; Weissman, Kira J. ; Takano, Eriko ; Sabatini, Stefano ; Stegmann, Evi ; Brötz, Heike ; Wohlleben, Wolfgang ; Seemann, Myriam ; Empting, Martin ; Hirsch, Anna K. H. ; Loretz, Brigitta ; Lehr, Claus-Michael ; Titz, Alexander ; Herrmann, Jennifer ; Jäger, Timo ; Alt, Silke ; Hesterkamp, Thomas ; Winterhalter, Mathias ; Schiefer, Andrea ; Pfarr, Kenneth ; Hoerauf, Achim ; Graz, Heather ; Graz, Michael ; Lindvall, Mika ; Ramurthy, Savithri ; Karlén, Anders ; Dongen, Maarten van ; Petkovic, Hrvoje ; Keller, Andreas ; Peyrane, Frédéric ; Donadio, Stefano ; Fraisse, Laurent ; Piddock, Laura J. V. ; Gilbert, Ian H. ; Moser, Heinz E. ; Müller, Rolf
An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.
Sardanelli, Francesco ; Aase, Hildegunn S. ; Álvarez, Marina ; Azavedo, Edward ; Baarslag, Henk J. ; Balleyguier, Corinne ; Baltzer, Pascal Andreas Thomas ; Beslagic, Vanesa ; Bick, Ulrich ; Bogdanovic-Stojanovic, Dragana ; Briediene, Ruta ; Brkljacic, Boris ; Camps Herrero, Julia ; Colin, Catherine ; Cornford, Eleanor ; Danes, Jan ; Geer, Gerard de ; Esen, Gul ; Evans, Andrew ; Fuchsjäger, Michael H. ; Gilbert, Fiona J. ; Graf, Oswald ; Hargaden, Gormlaith ; Helbich, Thomas H. ; Heywang-Köbrunner, Sylvia H. ; Ivanov, Valentin ; Jónsson, Ásbjörn ; Kuhl, Christiane Katharina ; Lisencu, Eugenia C. ; Luczynska, Elzbieta ; Mann, Ritse M. ; Marques, Jose C. ; Martincich, Laura ; Mortier, Margarete ; Müller-Schimpfle, Markus ; Ormandi, Katalin ; Panizza, Pietro ; Pediconi, Federica ; Pijnappel, Ruud M. ; Pinker, Katja ; Rissanen, Tarja ; Rotaru, Natalia ; Saguatti, Gianni ; Sella, Tamar ; Slobodníková, Jana ; Talk, Maret ; Taourel, Patrice ; Trimboli, Rubina Manuela ; Vejborg, Ilse ; Vourtsis, Athina ; Forrai, Gabor
EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50–69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1–10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40–49 years and 70–74 years, although with “limited evidence”. Thus, we firstly recommend biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40–45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become “routine mammography” in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged.
White, Helen ; Deprez, Liesbet ; Corbisier, Philippe ; Hall, Victoria ; Lin, Feng ; Mazoua, Stéphane ; Trapmann, Stefanie ; Aggerholm, Anni ; Andrikovics, Hajnalka ; Akiki, Susanna ; Barbany, Gisela ; Boeckx, Nancy ; Bench, Anthony ; Catherwood, Mark ; Cayuela, Jean-Michel ; Chudleigh, Sandra ; Clench, Tim ; Colomer, Dolors ; Daraio, Filomena ; Dulucq, Stephanie ; Farrugia, Joanna ; Fletcher, Linda ; Foroni, Letizia ; Ganderton, Ros ; Gerrard, Gareth ; Gineikienė, Eglė ; Hayette, Sandrine ; El Housni, Hakim ; Izzo, Barbara ; Jansson, Mattias ; Johnels, Petra ; Jurcek, Tomas ; Kairisto, Veli ; Kizilors, Aytug ; Kim, Dong-Wook ; Lange, Thoralf ; Lion, Thomas ; Polakova, Katerina Machova ; Martinelli, Giovanni ; McCarron, Sarah ; Merle, Pauline A. ; Milner, Ben ; Mitterbauer-Hohendanner, Gerlinde ; Nagar, Meital ; Nickless, Guillermina ; Nomdedéu, Josep F. ; Nymoen, Dag A. ; Leibundgut, Elisabeth Oppliger ; Ozbek, Ugur ; Pajič, Tadej ; Pfeifer, Heike ; Preudhomme, Claude ; Raudsepp, Kadri ; Romeo, Giuliana ; Sacha, Tomasz ; Talmaci, Rodica ; Touloumenidou, Tasoula ; Van der Velden, Vincent H. J. ; Waits, Paula ; Wang, Lihui ; Wilkinson, Elizabeth ; Wilson, Gill ; Wren, Dörte ; Zadro, Renata ; Ziermann, Janine ; Zoi, Katerina ; Müller, Martin C. ; Hochhaus, Andreas ; Schimmel, Heinz ; Cross, Nicholas C. P. ; Emons, Hendrik
Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).
Maier, Hannes ; Lenarz, Thomas ; Agha-Mir-Salim, Parwis ; Agterberg, Martijn J. H. ; Anagiotos, Andreas ; Arndt, Susan ; Ball, Geoffrey R. ; Bance, Manohar ; Barbara, Maurizio ; Baumann, Uwe ; Baumgartner, Wolfgang ; Bernardeschi, Daniele ; Beutner, Dirk ; Bosman, Arjan ; Briggs, Robert ; Busch, Susan ; Caversaccio, Marco ; Dahm, Markus ; Dalhoff, Ernst ; Devèze, Arnaud ; Ebrahimi-Madiseh, Azadeh ; Fraysse, Bernard ; Frenzel, Henning ; Gavilán, Javier ; Ghoncheh, Mohammad ; Håkansson, Bo E. V. ; Hodgetts, William ; Hol, Myrthe Karianne Sophie ; Holland, Julian ; Holmberg, Marcus ; Huber, Alexander ; Jenkins, Herman ; Katiri, Roulla ; Kheirkhah, Kiana ; Koitschev, Assen ; Kompis, Martin ; Lanting, Cris ; Lassaletta, Luis ; Lerut, Bob ; Leuwer, Rudolf ; Linder, Thomas ; Löwenheim, Hubert Martin ; Lustig, Lawrence ; Mandavia, Rishi ; Manrique, Manuel ; Jorge Humberto, Martins ; Mertens, Griet ; Mlynski, Robert Arndt ; Mojallal, Hamidreza ; Monini, Simonetta ; Monksfield, Peter ; Müller, Alexander ; Mylanus, Emmanuel ; Nakajima, Hideko Heidi ; Neudert, Marcus ; Offeciers, Erwin ; Pfiffner, Flurin ; Pietsch, Markus ; Plontke, Stefan K.-R. ; Prenzler, Nils Kristian ; Profant, Milan ; Rahne, Torsten ; Rajan, Gunesh ; Ratuszniak, Anna ; Raufer, Stefan ; Ray, Jaydip ; Reinfeldt, Sabine ; Röösli, Christof ; Rosenbom, Tove ; Salcher, Rolf Benedikt ; Schönermark, Matthias ; Schwab, Burkard ; Skarżyński, Henryk ; Skarżyński, Piotr H. ; Snapp, Hillary ; Sprinzl, Georg ; Spearman, Michael ; Stenfelt, Stefan ; Stieger, Christof ; Tringali, Stephane ; Truy, Eric ; Tysome, James ; Van de Heyning, Paul ; Verhaert, Nicolas ; Wesarg, Thomas ; Westerkull, Patrik ; Wollenberg, Barbara ; Zahnert, Thomas ; Zarowski, Andrzej ; Snik, Ad
Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
Wang, Mingyi ; Kong, Weimeng ; Marten, Ruby ; He, Xu-Cheng ; Chen, Dexian ; Pfeifer, Joschka ; Heitto, Arto ; Kontkanen, Jenni ; Dada, Lubna ; Kürten, Christoph Andreas ; Yli-Juuti, Taina ; Manninen, Hanna Elina ; Amanatidis, Stavros ; Amorim, Antonio ; Baalbaki, Rima ; Baccarini, Andrea ; Bell, David M. ; Bertozzi, Barbara ; Bräkling, Steffen ; Brilke, Sophia ; Murillo, Lucía Caudillo ; Chiu, Randall ; Chu, Biwu ; De Menezes, Louis-Philippe ; Duplissy, Jonathan ; Finkenzeller, Henning ; Gonzalez Carracedo, Loic ; Granzin, Manuel ; Guida, Roberto ; Hansel, Armin ; Hofbauer, Victoria ; Krechmer, Jordan ; Lehtipalo, Katrianne ; Lamkaddam, Houssni ; Lampimäki, Marku ; Lee, Chuan Ping ; Makhmutov, Vladimir ; Marie, Guillaume ; Mathot, Serge ; Mauldin, Roy Lee ; Mentler, Bernhard ; Müller, Tatjana ; Onnela, Antti ; Partoll, Eva ; Petäjä, Tuukka ; Philippov, Maxim ; Pospisilova, Veronika ; Ranjithkumar, Ananth ; Rissanen, Matti P. ; Rörup, Birte ; Scholz, Wiebke ; Shen, Jiali ; Simon, Mario ; Sipilä, Mikko ; Steiner, Gerhard ; Stolzenburg, Dominik ; Tham, Yee Jun ; Tomé, António ; Wagner, Andrea Christine ; Wang, Dongyu S. ; Wang, Yonghong ; Weber, Stefan K. ; Winkler, Paul M. ; Wlasits, Peter J. ; Wu, Yusheng ; Xiao, Mao ; Ye, Qing ; Zauner-Wieczorek, Marcel ; Zhou, Xueqin ; Volkamer, Rainer ; Riipinen, Ilona ; Dommen, Josef ; Curtius, Joachim ; Baltensperger, Urs ; Kulmala, Markku ; Worsnop, Douglas R. ; Kirkby, Jasper ; Seinfeld, John H. ; El Haddad, Imad ; Flagan, Richard C. ; Donahue, Neil McPherson
A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog, but how it occurs in cities is often puzzling. If the growth rates of urban particles are similar to those found in cleaner environments (1–10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below −15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid–base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms.
Robinson, Alan D. ; Millard, Genevieve A. ; Danis, François ; Guirlet, Marielle ; Harris, Neil R. P. ; Lee, Adrian M. ; McIntyre, J. D. ; Pyle, John A. ; Arvelius, Johan ; Dagnesjo, Saga ; Kirkwood, Sheila ; Nilsson, Hampus ; Toohey, Darin W. ; Deshler, Terry ; Goutail, Florence ; Pommereau, Jean-Pierre ; Elkins, James William ; Moore, Fred L. ; Ray, Eric ; Schmidt, Ulrich ; Engel, Andreas ; Müller, Melanie
Balloon-borne measurements of CFC-11 (on flights of the DIRAC in situ gas chromatograph and the DESCARTES grab sampler), ClO and O3 were made during the 1999/2000 winter as part of the SOLVE-THESEO 2000 campaign. Here we present the CFC-11 data from nine flights and compare them first with data from other instruments which flew during the campaign and then with the vertical distributions calculated by the SLIMCAT 3-D CTM. We calculate ozone loss inside the Arctic vortex between late January and early March using the relation between CFC-11 and O3 measured on the flights, the peak ozone loss (1200 ppbv) occurs in the 440–470 K region in early March in reasonable agreement with other published empirical estimates. There is also a good agreement between ozone losses derived from three independent balloon tracer data sets used here. The magnitude and vertical distribution of the loss derived from the measurements is in good agreement with the loss calculated from SLIMCAT over Kiruna for the same days.
Severe traumatic injury induces phenotypic and functional changes of neutrophils and monocytes
(2021)
Janicová, Andrea ; Becker, Nils ; Xu, Baolin ; Simic, Marija ; Noack, Laurens ; Wagner, Nils ; Müller, Andreas J. ; Bertrand, Jessica ; Marzi, Ingo ; Relja, Borna
Background: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. Methods: Peripheral blood was withdrawn from severely injured trauma patients (TP; n = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; n = 15) and stimulated with fMLP and PMA. CD16dimCD62Lbright (immature), CD16brightCD62Lbright (mature) and CD16brightCD62Ldim (CD62Llow) neutrophil subsets and CD14brightCD16− (classical), CD14brightCD16+ (intermediate) and CD14dimCD16+ (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of E. coli bioparticle phagocytosis were evaluated. Results: In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62Ldim neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62Ldim neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. Conclusions: Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury.
Robinson, Alan D. ; Millard, Genevieve A. ; Danis, François ; Guirlet, Marielle ; Harris, Neil R. P. ; Lee, Adrian M. ; McIntyre, J. D. ; Pyle, John A. ; Arvelius, Johan ; Dagnesjo, Saga ; Kirkwood, Sheila ; Nilsson, Hampus ; Toohey, Darin W. ; Deshler, Terry ; Goutail, Florence ; Pommereau, Jean-Pierre ; Elkins, James William ; Moore, Fred L. ; Ray, Eric ; Schmidt, Ulrich ; Engel, Andreas ; Müller, Melanie
Balloon-borne measurements of CFC11 (from the DIRAC in situ gas chromatograph and the DESCARTES grab sampler), ClO and O3 were made during the 1999/2000 Arctic winter as part of the SOLVE-THESEO 2000 campaign, based in Kiruna (Sweden). Here we present the CFC11 data from nine flights and compare them first with data from other instruments which flew during the campaign and then with the vertical distributions calculated by the SLIMCAT 3D CTM. We calculate ozone loss inside the Arctic vortex between late January and early March using the relation between CFC11 and O3 measured on the flights. The peak ozone loss (~1200ppbv) occurs in the 440-470K region in early March in reasonable agreement with other published empirical estimates. There is also a good agreement between ozone losses derived from three balloon tracer data sets used here. The magnitude and vertical distribution of the loss derived from the measurements is in good agreement with the loss calculated from SLIMCAT over Kiruna for the same days.
Andlauer, Till ; Guzman-Parra, José ; Streit, Fabian ; Strohmaier, Jana ; González, Maria José ; Flores, Susana Gil ; Cabaleiro Fabeiro, Francisco J. ; Rı́o Noriega, Francisco del ; Perez, Fermin Perez ; González, Jesus Haro ; Orozco Diaz, Guillermo ; de Diego-Otero, Yolanda ; Moreno-Kuestner, Berta ; Auburger, Georg ; Degenhardt, Franziska ; Heilmann-Heimbach, Stefanie ; Herms, Stefan ; Hoffmann, Per ; Frank, Josef ; Foo, Jerome Clifford ; Treutlein, Jens ; Witt, Stephanie H. ; Cichon, Sven ; Kogevinas, Manolis ; Rivas, Fabio ; Mayoral, Fermı́n ; Müller-Myhsok, Bertram ; Forstner, Andreas Josef ; Nöthen, Markus Maria ; Rietschel, Marcella
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.
Andlauer, Till ; Guzman-Parra, José ; Streit, Fabian ; Strohmaier, Jana ; González, Maria José ; Flores, Susana Gil ; Cabaleiro Fabeiro, Francisco J. ; Rı́o Noriega, Francisco del ; Perez, Fermin Perez ; González, Jesus Haro ; Orozco Diaz, Guillermo ; de Diego-Otero, Yolanda ; Moreno-Kuestner, Berta ; Auburger, Georg ; Degenhardt, Franziska ; Heilmann-Heimbach, Stefanie ; Herms, Stefan ; Hoffmann, Per ; Frank, Josef ; Foo, Jerome Clifford ; Treutlein, Jens ; Witt, Stephanie H. ; Cichon, Sven ; Kogevinas, Manolis ; Rivas, Fabio ; Mayoral, Fermı́n ; Müller-Myhsok, Bertram ; Forstner, Andreas Josef ; Nöthen, Markus Maria ; Rietschel, Marcella
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.