TY - JOUR A1 - Hudson, Lawrence N. A1 - Newbold, Tim A1 - Contu, Sara A1 - Hill, Samantha L. L. A1 - Lysenko, Igor A1 - De Palma, Adriana A1 - Phillips, Helen R. P. A1 - Senior, Rebecca A. A1 - Bennett, Dominic J. A1 - Booth, Hollie A1 - Choimes, Argyrios A1 - Correia, David L. P. A1 - Day, Julie A1 - Echeverria-Londono, Susy A1 - Garon, Morgan A1 - Harrison, Michelle L. K. A1 - Ingram, Daniel J. A1 - Jung, Martin A1 - Kemp, Victoria A1 - Kirkpatrick, Lucinda A1 - Martin, Callum D. A1 - Pan, Yuan A1 - White, Hannah J. A1 - Aben, Job A1 - Abrahamczyk, Stefan A1 - Adum, Gilbert B. A1 - Aguilar-Barquero, Virginia A1 - Aizen, Marcelo A1 - Ancrenaz, Marc A1 - Arbelaez-Cortes, Enrique A1 - Armbrecht, Inge A1 - Azhar, Badrul A1 - Azpiroz, Adrian B. A1 - Baeten, Lander A1 - Báldi, András A1 - Banks, John E. A1 - Barlow, Jos A1 - Batáry, Péter A1 - Bates, Adam J. A1 - Bayne, Erin M. A1 - Beja, Pedro A1 - Berg, Ake A1 - Berry, Nicholas J. A1 - Bicknell, Jake E. A1 - Bihn, Jochen H. A1 - Böhning-Gaese, Katrin A1 - Boekhout, Teun A1 - Boutin, Celine A1 - Bouyer, Jeremy A1 - Brearley, Francis Q. A1 - Brito, Isabel A1 - Brunet, Jörg A1 - Buczkowski, Grzegorz A1 - Buscardo, Erika A1 - Cabra-Garcia, Jimmy A1 - Calvino-Cancela, Maria A1 - Cameron, Sydney A. A1 - Cancello, Eliana M. A1 - Carrijo, Tiago F. A1 - Carvalho, Anelena L. A1 - Castro, Helena A1 - Castro-Luna, Alejandro A. A1 - Cerda, Rolando A1 - Cerezo, Alexis A1 - Chauvat, Matthieu A1 - Clarke, Frank M. A1 - Cleary, Daniel F. R. A1 - Connop, Stuart P. A1 - D'Aniello, Biagio A1 - da Silva, Pedro Giovani A1 - Darvill, Ben A1 - Dauber, Jens A1 - Dejean, Alain A1 - Diekötter, Tim A1 - Dominguez-Haydar, Yamileth A1 - Dormann, Carsten F. A1 - Dumont, Bertrand A1 - Dures, Simon G. A1 - Dynesius, Mats A1 - Edenius, Lars A1 - Elek, Zoltán A1 - Entling, Martin H. A1 - Farwig, Nina A1 - Fayle, Tom M. A1 - Felicioli, Antonio A1 - Felton, Annika M. A1 - Ficetola, Gentile F. A1 - Filgueiras, Bruno K. C. A1 - Fonte, Steve J. A1 - Fraser, Lauchlan H. A1 - Fukuda, Daisuke A1 - Furlani, Dario A1 - Ganzhorn, Jörg U. A1 - Garden, Jenni G. A1 - Gheler-Costa, Carla A1 - Giordani, Paolo A1 - Giordano, Simonetta A1 - Gottschalk, Marco S. A1 - Goulson, Dave A1 - Gove, Aaron D. A1 - Grogan, James A1 - Hanley, Mick E. A1 - Hanson, Thor A1 - Hashim, Nor R. A1 - Hawes, Joseph E. A1 - Hébert, Christian A1 - Helden, Alvin J. A1 - Henden, John-André A1 - Hernández, Lionel A1 - Herzog, Felix A1 - Higuera-Diaz, Diego A1 - Hilje, Branko A1 - Horgan, Finbarr G. A1 - Horváth, Roland A1 - Hylander, Kristoffer A1 - Horváth, Roland A1 - Isaacs-Cubides, Paola A1 - Ishitani, Mashiro A1 - Jacobs, Carmen T. A1 - Jaramillo, Victor J. A1 - Jauker, Birgit A1 - Jonsell, Matts A1 - Jung, Thomas S. A1 - Kapoor, Vena A1 - Kati, Vassiliki A1 - Katovai, Eric A1 - Kessler, Michael A1 - Knop, Eva A1 - Kolb, Annette A1 - Körösi, Àdám A1 - Lachat, Thibault A1 - Lantschner, Victoria A1 - Le Féon, Violette A1 - LeBuhn, Gretchen A1 - Légaré, Jean-Philippe A1 - Letcher, Susan G. A1 - Littlewood, Nick A. A1 - López-Quintero, Carlos A. A1 - Louhaichi, Mounir A1 - Lövei, Gabor L. A1 - Lucas-Borja, Manuel Esteban A1 - Luja, Victor H. A1 - Maeto, Kaoru A1 - Magura, Tibor A1 - Mallari, Neil Aldrin A1 - Marin-Spiotta, Erika A1 - Marhall, E. J. P. A1 - Martínez, Eliana A1 - Mayfield, Margaret M. A1 - Mikusinski, Gregorz A1 - Milder, Jeffery C. A1 - Miller, James R. A1 - Morales, Carolina L. A1 - Muchane, Mary N. A1 - Muchane, Muchai A1 - Naidoo, Robin A1 - Nakamura, Akihiro A1 - Naoe, Shoji A1 - Nates-Parra, Guiomar A1 - Navarerete Gutierrez, Dario A. A1 - Neuschulz, Eike L. A1 - Noreika, Norbertas A1 - Norfolk, Olivia A1 - Noriega, Jorge Ari A1 - Nöske, Nicole M. A1 - O'Dea, Niall A1 - Oduro, William A1 - Ofori-Boateng, Caleb A1 - Oke, Chris O. A1 - Osgathorpe, Lynne M. A1 - Paritsis, Juan A1 - Parrah, Alejandro A1 - Pelegrin, Nicolás A1 - Peres, Carlos A. A1 - Persson, Anna S. A1 - Petanidou, Theodora A1 - Phalan, Ben A1 - Philips, T. Keith A1 - Poveda, Katja A1 - Power, Eileen F. A1 - Presley, Steven J. A1 - Proença, Vânia A1 - Quaranta, Marino A1 - Quintero, Carolina A1 - Redpath-Downing, Nicola A. A1 - Reid, J. Leighton A1 - Reis, Yana T. A1 - Ribeiro, Danilo B. A1 - Richardson, Barbara A. A1 - Richardson, Michael J. A1 - Robles, Carolina A. A1 - Römbke, Jörg A1 - Romero-Duque, Luz Piedad A1 - Rosselli, Loreta A1 - Rossiter, Stephen J. A1 - Roulston, T'ai H. A1 - Rousseau, Laurent A1 - Sadler, Jonathan P. A1 - Sáfián, Szbolcs A1 - Saldaña-Vásquez, Romeo A. A1 - Samnegård, Ulrika A1 - Schüepp, Christof A1 - Schweiger, Oliver A1 - Sedlock, Jodi L. A1 - Shahabuddin, Ghazala A1 - Sheil, Douglas A1 - Silva, Fernando A. B. A1 - Slade, Eleanor A1 - Smith-Pardo, Allan H. A1 - Sodhi, Navjot S. A1 - Somarriba, Eduardo J. A1 - Sosa, Ramón A. A1 - Stout, Jane C. A1 - Struebig, Matthew J. A1 - Sung, Yik-Hei A1 - Threlfall, Caragh G. A1 - Tonietto, Rebecca A1 - Tóthmérész, Béla A1 - Tscharntke, Teja A1 - Turner, Edgar C. A1 - Tylianakis, Jason M. A1 - Vanbergen, Adam J. A1 - Vassilev, Kiril A1 - Verboven, Hans A. F. A1 - Vergara, Carlos H. A1 - Vergara, Pablo M. A1 - Verhulst, Jort A1 - Walker, Tony R. A1 - Wang, Yanping A1 - Watling, James I. A1 - Wells, Konstans A1 - Williams, Christopher D. A1 - Willig, Michael R. A1 - Woinarski, John C. Z. A1 - Wolf, Jan H. D. A1 - Woodcock, Ben A. A1 - Yu, Douglas W. A1 - Zailsev, Andreys A1 - Collen, Ben A1 - Ewers, Rob M. A1 - Mace, Georgina M. A1 - Purves, Drew W. A1 - Scharlemann, Jörn P. W. A1 - Pervis, Andy T1 - The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts JF - Ecology and Evolution N2 - Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015. KW - urban-rural gradient KW - instensively managed farmland KW - Mexican coffee plantations KW - Bombus Spp. Hymenoptera KW - bumblebee nest density KW - data sharing KW - land use KW - habitat destruction KW - global change KW - land-use change KW - plant community composition KW - Northeastern Costa Rica KW - dung beetle coleoptera KW - bird species richness Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114425 VL - 4 IS - 24 ER - TY - JOUR A1 - Gröbner, Susanne N. A1 - Worst, Barbara C. A1 - Weischenfeldt, Joachim A1 - Buchhalter, Ivo A1 - Kleinheinz, Kortine A1 - Rudneva, Vasilisa A. A1 - Johann, Pascal D. A1 - Balasubramanian, Gnana Prakash A1 - Segura-Wang, Maia A1 - Brabetz, Sebastian A1 - Bender, Sebastian A1 - Hutter, Barbara A1 - Sturm, Dominik A1 - Pfaff, Elke A1 - Hübschmann, Daniel A1 - Zipprich, Gideon A1 - Heinold, Michael A1 - Eils, Jürgen A1 - Lawerenz, Christian A1 - Erkek, Serap A1 - Lambo, Sander A1 - Waszak, Sebastian A1 - Blattmann, Claudia A1 - Borkhardt, Arndt A1 - Kuhlen, Michaela A1 - Eggert, Angelika A1 - Fulda, Simone A1 - Gessler, Manfred A1 - Wegert, Jenny A1 - Kappler, Roland A1 - Baumhoer, Daniel A1 - Stefan, Burdach A1 - Kirschner-Schwabe, Renate A1 - Kontny, Udo A1 - Kulozik, Andreas E. A1 - Lohmann, Dietmar A1 - Hettmer, Simone A1 - Eckert, Cornelia A1 - Bielack, Stefan A1 - Nathrath, Michaela A1 - Niemeyer, Charlotte A1 - Richter, Günther H. A1 - Schulte, Johannes A1 - Siebert, Reiner A1 - Westermann, Frank A1 - Molenaar, Jan J. A1 - Vassal, Gilles A1 - Witt, Hendrik A1 - Burkhardt, Birgit A1 - Kratz, Christian P. A1 - Witt, Olaf A1 - van Tilburg, Cornelis M. A1 - Kramm, Christof M. A1 - Fleischhack, Gudrun A1 - Dirksen, Uta A1 - Rutkowski, Stefan A1 - Frühwald, Michael A1 - Hoff, Katja von A1 - Wolf, Stephan A1 - Klingebeil, Thomas A1 - Koscielniak, Ewa A1 - Landgraf, Pablo A1 - Koster, Jan A1 - Resnick, Adam C. A1 - Zhang, Jinghui A1 - Liu, Yanling A1 - Zhou, Xin A1 - Waanders, Angela J. A1 - Zwijnenburg, Danny A. A1 - Raman, Pichai A1 - Brors, Benedikt A1 - Weber, Ursula D. A1 - Northcott, Paul A. A1 - Pajtler, Kristian W. A1 - Kool, Marcel A1 - Piro, Rosario M. A1 - Korbel, Jan O. A1 - Schlesner, Matthias A1 - Eils, Roland A1 - Jones, David T. W. A1 - Lichter, Peter A1 - Chavez, Lukas A1 - Zapatka, Marc A1 - Pfister, Stefan M. T1 - The landscape of genomic alterations across childhood cancers JF - Nature N2 - Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials. KW - cancer genomics KW - oncogenesis KW - paediatric cancer KW - predictive markers KW - translational research Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229579 VL - 555 ER - TY - JOUR A1 - Rodríguez-Mari, Adriana A1 - Wilson, Catherine A1 - Titus, Tom A. A1 - Canestro, Cristian A1 - BreMiller, Ruth A. A1 - Yan, Yi-Lin A1 - Nanda, Indrajit A1 - Johnston, Adam A1 - Kanki, John P. A1 - Gray, Erin M. A1 - He, Xinjun A1 - Spitsbergen, Jan A1 - Schindler, Detlev A1 - Postlethwait, John H. T1 - Roles of brca2 (fancd1) in Oocyte Nuclear Architecture, Gametogenesis, Gonad Tumors, and Genome Stability in Zebrafish JF - PLoS Genetics N2 - Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: (25.0 +/- 2.8) years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes (V(gray)) traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of (23.6 +/- 0.7) mm considering the deepest 5% of light. Of the detected photon packages scalp and bone absorbed (96.4 +/- 9: 7)% and V(gray) absorbed (3.1 +/- 1.8)% of the energy. The mean V(gray) volume (1.1 +/- 0.4)cm(3) was negatively correlated (r = - .76) with the SCD and frontal sinus volume (r = - .57) and was reduced by 41.5% in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD (r = .46) and the traversed frontal sinus volume (r = .43). Sulcal morphology had no significant impact on V(gray). Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance. KW - oocytes KW - zebrafish KW - genetic causes of cancer KW - testes KW - apoptosis KW - gonads KW - sperm KW - embryos Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142285 VL - 7 IS - 3 ER - TY - JOUR A1 - Blanco, Ignacio A1 - Kuchenbaecker, Karoline A1 - Cuadras, Daniel A1 - Wang, Xianshu A1 - Barrowdale, Daniel A1 - Ruiz de Garibay, Gorka A1 - Librado, Pablo A1 - Sanchez-Gracia, Alejandro A1 - Rozas, Julio A1 - Bonifaci, Núria A1 - McGuffog, Lesley A1 - Pankratz, Vernon S. A1 - Islam, Abul A1 - Mateo, Francesca A1 - Berenguer, Antoni A1 - Petit, Anna A1 - Català, Isabel A1 - Brunet, Joan A1 - Feliubadaló, Lidia A1 - Tornero, Eva A1 - Benítez, Javier A1 - Osorio, Ana A1 - Ramón y Cajal, Teresa A1 - Nevanlinna, Heli A1 - Aittomäki, Kristina A1 - Arun, Banu K. A1 - Toland, Amanda E. A1 - Karlan, Beth Y. A1 - Walsh, Christine A1 - Lester, Jenny A1 - Greene, Mark H. A1 - Mai, Phuong L. A1 - Nussbaum, Robert L. A1 - Andrulis, Irene L. A1 - Domchek, Susan M. A1 - Nathanson, Katherine L. A1 - Rebbeck, Timothy R. A1 - Barkardottir, Rosa B. A1 - Jakubowska, Anna A1 - Lubinski, Jan A1 - Durda, Katarzyna A1 - Jaworska-Bieniek, Katarzyna A1 - Claes, Kathleen A1 - Van Maerken, Tom A1 - Díez, Orland A1 - Hansen, Thomas V. A1 - Jønson, Lars A1 - Gerdes, Anne-Marie A1 - Ejlertsen, Bent A1 - De la Hoya, Miguel A1 - Caldés, Trinidad A1 - Dunning, Alison M. A1 - Oliver, Clare A1 - Fineberg, Elena A1 - Cook, Margaret A1 - Peock, Susan A1 - McCann, Emma A1 - Murray, Alex A1 - Jacobs, Chris A1 - Pichert, Gabriella A1 - Lalloo, Fiona A1 - Chu, Carol A1 - Dorkins, Huw A1 - Paterson, Joan A1 - Ong, Kai-Ren A1 - Teixeira, Manuel R. A1 - Hogervorst, Frans B. L. A1 - Van der Hout, Annemarie H. A1 - Seynaeve, Caroline A1 - Van der Luijt, Rob B. A1 - Ligtenberg, Marjolijn J. L. A1 - Devilee, Peter A1 - Wijnen, Juul T. A1 - Rookus, Matti A. A1 - Meijers-Heijboer, Hanne E. J. A1 - Blok, Marinus J. A1 - Van den Ouweland, Ans M. W. A1 - Aalfs, Cora M. A1 - Rodriguez, Gustavo C. A1 - Phillips, Kelly-Anne A. A1 - Piedmonte, Marion A1 - Nerenstone, Stacy R. A1 - Bae-Jump, Victoria L. A1 - O'Malley, David M. A1 - Schmutzler, Rita K. A1 - Wappenschmidt, Barbara A1 - Rhiem, Kerstin A1 - Engel, Christoph A1 - Meindl, Alfons A1 - Ditsch, Nina A1 - Arnold, Norbert A1 - Plendl, Hansjoerg J. A1 - Niederacher, Dieter A1 - Sutter, Christian A1 - Wang-Gohrke, Shan A1 - Steinemann, Doris A1 - Preisler-Adams, Sabine A1 - Kast, Karin A1 - Varon-Mateeva, Raymonda A1 - Gehrig, Andrea A1 - Bojesen, Anders A1 - Pedersen, Inge Sokilde A1 - Sunde, Lone A1 - Birk Jensen, Uffe A1 - Thomassen, Mads A1 - Kruse, Torben A. A1 - Foretova, Lenka A1 - Peterlongo, Paolo A1 - Bernard, Loris A1 - Peissel, Bernard A1 - Scuvera, Giulietta A1 - Manoukian, Siranoush A1 - Radice, Paolo A1 - Ottini, Laura A1 - Montagna, Marco A1 - Agata, Simona A1 - Maugard, Christine A1 - Simard, Jacques A1 - Soucy, Penny A1 - Berger, Andreas A1 - Fink-Retter, Anneliese A1 - Singer, Christian F. A1 - Rappaport, Christine A1 - Geschwantler-Kaulich, Daphne A1 - Tea, Muy-Kheng A1 - Pfeiler, Georg A1 - John, Esther M. A1 - Miron, Alex A1 - Neuhausen, Susan L. A1 - Terry, Mary Beth A1 - Chung, Wendy K. A1 - Daly, Mary B. A1 - Goldgar, David E. A1 - Janavicius, Ramunas A1 - Dorfling, Cecilia M. A1 - Van Rensburg, Elisabeth J. A1 - Fostira, Florentia A1 - Konstantopoulou, Irene A1 - Garber, Judy A1 - Godwin, Andrew K. A1 - Olah, Edith A1 - Narod, Steven A. A1 - Rennert, Gad A1 - Paluch, Shani Shimon A1 - Laitman, Yael A1 - Friedman, Eitan A1 - Liljegren, Annelie A1 - Rantala, Johanna A1 - Stenmark-Askmalm, Marie A1 - Loman, Niklas A1 - Imyanitov, Evgeny N. A1 - Hamann, Ute A1 - Spurdle, Amanda B. A1 - Healey, Sue A1 - Weitzel, Jeffrey N. A1 - Herzog, Josef A1 - Margileth, David A1 - Gorrini, Chiara A1 - Esteller, Manel A1 - Gómez, Antonio A1 - Sayols, Sergi A1 - Vidal, Enrique A1 - Heyn, Holger A1 - Stoppa-Lyonnet, Dominique A1 - Léoné, Melanie A1 - Barjhoux, Laure A1 - Fassy-Colcombet, Marion A1 - Pauw, Antoine de A1 - Lasset, Christine A1 - Fert Ferrer, Sandra A1 - Castera, Laurent A1 - Berthet, Pascaline A1 - Cornelis, François A1 - Bignon, Yves-Jean A1 - Damiola, Francesca A1 - Mazoyer, Sylvie A1 - Sinilnikova, Olga M. A1 - Maxwell, Christopher A. A1 - Vijai, Joseph A1 - Robson, Mark A1 - Kauff, Noah A1 - Corines, Marina J. A1 - Villano, Danylko A1 - Cunningham, Julie A1 - Lee, Adam A1 - Lindor, Noralane A1 - Lázaro, Conxi A1 - Easton, Douglas F. A1 - Offit, Kenneth A1 - Chenevix-Trench, Georgia A1 - Couch, Fergus J. A1 - Antoniou, Antonis C. A1 - Pujana, Miguel Angel T1 - Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers JF - PLoS ONE N2 - While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10\(^{-4}\) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p\(_{interaction}\) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. KW - genetic interaction networks KW - genome-wide association KW - expression signature KW - susceptibility loci KW - survival KW - modifiers KW - polymorphism KW - cell KW - chip-seq KW - elements Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143469 VL - 10 IS - 4 ER - TY - JOUR A1 - Couch, Fergus J. A1 - Wang, Xianshu A1 - McGuffog, Lesley A1 - Lee, Andrew A1 - Olswold, Curtis A1 - Kuchenbaecker, Karoline B. A1 - Soucy, Penny A1 - Fredericksen, Zachary A1 - Barrowdale, Daniel A1 - Dennis, Joe A1 - Gaudet, Mia M. A1 - Dicks, Ed A1 - Kosel, Matthew A1 - Healey, Sue A1 - Sinilnikova, Olga M. A1 - Lee, Adam A1 - Bacot, Françios A1 - Vincent, Daniel A1 - Hogervorst, Frans B. L. A1 - Peock, Susan A1 - Stoppa-Lyonnet, Dominique A1 - Jakubowska, Anna A1 - Radice, Paolo A1 - Schmutzler, Rita Katharina A1 - Domchek, Susan M. A1 - Piedmonte, Marion A1 - Singer, Christian F. A1 - Friedman, Eitan A1 - Thomassen, Mads A1 - Hansen, Thomas V. O. A1 - Neuhausen, Susan L. A1 - Szabo, Csilla I. A1 - Blanco, Ingnacio A1 - Greene, Mark H. A1 - Karlan, Beth Y. A1 - Garber, Judy A1 - Phelan, Catherine M. A1 - Weitzel, Jeffrey N. A1 - Montagna, Marco A1 - Olah, Edith A1 - Andrulis, Irene L. A1 - Godwin, Andrew K. A1 - Yannoukakos, Drakoulis A1 - Goldgar, David E. A1 - Caldes, Trinidad A1 - Nevanlinna, Heli A1 - Osorio, Ana A1 - Terry, Mary Beth A1 - Daly, Mary B. A1 - van Rensburg, Elisabeth J. A1 - Hamann, Ute A1 - Ramus, Susan J. A1 - Toland, Amanda Ewart A1 - Caligo, Maria A. A1 - Olopade, Olufunmilayo I. A1 - Tung, Nadine A1 - Claes, Kathleen A1 - Beattie, Mary S. A1 - Southey, Melissa C. A1 - Imyanitov, Evgeny N. A1 - Tischkowitz, Marc A1 - Janavicius, Ramunas A1 - John, Esther M. A1 - Kwong, Ava A1 - Diez, Orland A1 - Kwong, Ava A1 - Balmaña, Judith A1 - Barkardottir, Rosa B. A1 - Arun, Banu K. A1 - Rennert, Gad A1 - Teo, Soo-Hwang A1 - Ganz, Patricia A. A1 - Campbell, Ian A1 - van der Hout, Annemarie H. A1 - van Deurzen, Carolien H. M. A1 - Seynaeve, Caroline A1 - Garcia, Encarna B. Gómez A1 - van Leeuwen, Flora E. A1 - Meijers-Heijboer, Hanne E. J. A1 - Gille, Johannes J. P. A1 - Ausems, Magreet G. E. M. A1 - Blok, Marinus J. A1 - Ligtenberg, Marjolinjin J. L. A1 - Rookus, Matti A. A1 - Devilee, Peter A1 - Verhoef, Senno A1 - van Os, Theo A. M. A1 - Wijnen, Juul T. A1 - Frost, Debra A1 - Ellis, Steve A1 - Fineberg, Elena A1 - Platte, Radke A1 - Evans, D. Gareth A1 - Izatt, Luise A1 - Eeles, Rosalind A. A1 - Adlard, Julian A1 - Eccles, Diana M. A1 - Cook, Jackie A1 - Brewer, Carole A1 - Douglas, Fiona A1 - Hodgson, Shirley A1 - Morrison, Patrick J. A1 - Side, Lucy E. A1 - Donaldson, Alan A1 - Houghton, Catherine A1 - Rogers, Mark T. A1 - Dorkins, Huw A1 - Eason, Jacqueline A1 - Gregory, Helen A1 - McCann, Emma A1 - Murray, Alex A1 - Calender, Alain A1 - Hardouin, Agnès A1 - Berthet, Pascaline A1 - Delnatte, Capucine A1 - Nogues, Catherine A1 - Lasset, Christine A1 - Houdayer, Claude A1 - Leroux,, Dominique A1 - Rouleau, Etienne A1 - Prieur, Fabienne A1 - Damiola, Francesca A1 - Sobol, Hagay A1 - Coupier, Isabelle A1 - Venat-Bouvet, Laurence A1 - Castera, Laurent A1 - Gauthier-Villars, Marion A1 - Léoné, Mélanie A1 - Pujol, Pascal A1 - Mazoyer, Sylvie A1 - Bignon, Yves-Jean A1 - Zlowocka-Perlowska, Elzbieta A1 - Gronwald, Jacek A1 - Lubinski,, Jan A1 - Durda, Katarzyna A1 - Jaworska, Katarzyna A1 - Huzarski, Tomasz A1 - Spurdle, Amanda B. A1 - Viel, Alessandra A1 - Peissel, Bernhard A1 - Bonanni, Bernardo A1 - Melloni, Guilia A1 - Ottini, Laura A1 - Papi, Laura A1 - Varesco, Liliana A1 - Tibiletti, Maria Grazia A1 - Peterlongo, Paolo A1 - Volorio, Sara A1 - Manoukian, Siranoush A1 - Pensotti, Valeria A1 - Arnold, Norbert A1 - Engel, Christoph A1 - Deissler, Helmut A1 - Gadzicki, Dorothea A1 - Gehrig, Andrea A1 - Kast, Karin A1 - Rhiem, Kerstin A1 - Meindl, Alfons A1 - Niederacher, Dieter A1 - Ditsch, Nina A1 - Plendl, Hansjoerg A1 - Preisler-Adams, Sabine A1 - Engert, Stefanie A1 - Sutter, Christian A1 - Varon-Mateeva, Raymenda A1 - Wappenschmidt, Barbara A1 - Weber, Bernhard H. F. A1 - Arver, Brita A1 - Stenmark-Askmalm, Marie A1 - Loman, Niklas A1 - Rosenquist, Richard A1 - Einbeigi, Zakaria A1 - Nathanson, Katherine L. A1 - Rebbeck, Timothy R. A1 - Blank, Stephanie V. A1 - Cohn, David E. A1 - Rodriguez, Gustavo C. A1 - Small, Laurie A1 - Friedlander, Michael A1 - Bae-Jump, Victoria L. A1 - Fink-Retter, Anneliese A1 - Rappaport, Christine A1 - Gschwantler-Kaulich, Daphne A1 - Pfeiler, Georg A1 - Tea, Muy-Kheng A1 - Lindor, Noralane M. A1 - Kaufman, Bella A1 - Paluch, Shani Shimon A1 - Laitman, Yael A1 - Skytte, Anne-Bine A1 - Gerdes, Anne-Marie A1 - Pedersen, Inge Sokilde A1 - Moeller, Sanne Traasdahl A1 - Kruse, Torben A. A1 - Jensen, Uffe Birk A1 - Vijai, Joseph A1 - Sarrel, Kara A1 - Robson, Mark A1 - Kauff, Noah A1 - Mulligan, Anna Marie A1 - Glendon, Gord A1 - Ozcelik, Hilmi A1 - Ejlertsen, Bent A1 - Nielsen, Finn C. A1 - Jønson, Lars A1 - Andersen, Mette K. A1 - Ding, Yuan Chun A1 - Steele, Linda A1 - Foretova, Lenka A1 - Teulé, Alex A1 - Lazaro, Conxi A1 - Brunet, Joan A1 - Pujana, Miquel Angel A1 - Mai, Phuong L. A1 - Loud, Jennifer T. A1 - Walsh, Christine A1 - Lester, Jenny A1 - Orsulic, Sandra A1 - Narod, Steven A. A1 - Herzog, Josef A1 - Sand, Sharon R. A1 - Tognazzo, Silvia A1 - Agata, Simona A1 - Vaszko, Tibor A1 - Weaver, Joellen A1 - Stravropoulou, Alexandra V. A1 - Buys, Saundra S. A1 - Romero, Atocha A1 - de la Hoya, Miguel A1 - Aittomäki, Kristiina A1 - Muranen, Taru A. A1 - Duran, Mercedes A1 - Chung, Wendy K. A1 - Lasa, Adriana A1 - Dorfling, Cecilia M. A1 - Miron, Alexander A1 - Benitez, Javier A1 - Senter, Leigha A1 - Huo, Dezheng A1 - Chan, Salina B. A1 - Sokolenko, Anna P. A1 - Chiquette, Jocelyne A1 - Tihomirova, Laima A1 - Friebel, Tara M. A1 - Agnarsson, Bjarne A. A1 - Lu, Karen H. A1 - Lejbkowicz, Flavio A1 - James, Paul A. A1 - Hall, Per A1 - Dunning, Alison M. A1 - Tessier, Daniel A1 - Cunningham, Julie A1 - Slager, Susan L. A1 - Chen, Wang A1 - Hart, Steven A1 - Stevens, Kristen A1 - Simard, Jacques A1 - Pastinen, Tomi A1 - Pankratz, Vernon S. A1 - Offit, Kenneth A1 - Easton, Douglas F. A1 - Chenevix-Trench, Georgia A1 - Antoniou, Antonis C. T1 - Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk JF - PLOS Genetics N2 - BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. KW - common variants KW - susceptibility alleles KW - genetic variants KW - modifiers KW - ZNF365 KW - investigators KW - population KW - consortium KW - selection KW - subtypes Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127947 SN - 1553-7404 VL - 9 IS - 3 ER - TY - JOUR A1 - Manchia, Mirko A1 - Adli, Mazda A1 - Akula, Nirmala A1 - Arda, Raffaella A1 - Aubry, Jean-Michel A1 - Backlund, Lena A1 - Banzato, Claudio E. M. A1 - Baune, Bernhard T. A1 - Bellivier, Frank A1 - Bengesser, Susanne A1 - Biernacka, Joanna M. A1 - Brichant-Petitjean, Clara A1 - Bui, Elise A1 - Calkin, Cynthia V. A1 - Cheng, Andrew Tai Ann A1 - Chillotti, Caterina A1 - Cichon, Sven A1 - Clark, Scott A1 - Czerski, Piotr M. A1 - Dantas, Clarissa A1 - Del Zompo, Maria A1 - DePaulo, J. Raymond A1 - Detera-Wadleigh, Sevilla D. A1 - Etain, Bruno A1 - Falkai, Peter A1 - Frisén, Louise A1 - Frye, Mark A. A1 - Fullerton, Jan A1 - Gard, Sébastien A1 - Garnham, Julie A1 - Goes, Fernando S. A1 - Grof, Paul A1 - Gruber, Oliver A1 - Hashimoto, Ryota A1 - Hauser, Joanna A1 - Heilbronner, Urs A1 - Hoban, Rebecca A1 - Hou, Liping A1 - Jamain, Stéphane A1 - Kahn, Jean-Pierre A1 - Kassem, Layla A1 - Kato, Tadafumi A1 - Kelsoe, John R. A1 - Kittel-Schneider, Sarah A1 - Kliwicki, Sebastian A1 - Kuo, Po-Hsiu A1 - Kusumi, Ichiro A1 - Laje, Gonzalo A1 - Lavebratt, Catharina A1 - Leboyer, Marion A1 - Leckband, Susan G. A1 - López Jaramillo, Carlos A. A1 - Maj, Mario A1 - Malafosse, Alain A1 - Martinsson, Lina A1 - Masui, Takuya A1 - Mitchell, Philip B. A1 - Mondimore, Frank A1 - Monteleone, Palmiero A1 - Nallet, Audrey A1 - Neuner, Maria A1 - Novák, Tomás A1 - O'Donovan, Claire A1 - Ösby, Urban A1 - Ozaki, Norio A1 - Perlis, Roy H. A1 - Pfennig, Andrea A1 - Potash, James B. A1 - Reich-Erkelenz, Daniela A1 - Reif, Andreas A1 - Reininghaus, Eva A1 - Richardson, Sara A1 - Rouleau, Guy A. A1 - Rybakowski, Janusz K. A1 - Schalling, Martin A1 - Schofield, Peter R. A1 - Schubert, Oliver K. A1 - Schweizer, Barbara A1 - Seemüller, Florian A1 - Grigoroiu-Serbanescu, Maria A1 - Severino, Giovanni A1 - Seymour, Lisa R. A1 - Slaney, Claire A1 - Smoller, Jordan W. A1 - Squassina, Alessio A1 - Stamm, Thomas A1 - Steele, Jo A1 - Stopkova, Pavla A1 - Tighe, Sarah K. A1 - Tortorella, Alfonso A1 - Turecki, Gustavo A1 - Wray, Naomi R. A1 - Wright, Adam A1 - Zandi, Peter P. A1 - Zilles, David A1 - Bauer, Michael A1 - Rietschel, Marcella A1 - McMahon, Francis J. A1 - Schulze, Thomas G. A1 - Alda, Martin T1 - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report JF - PLoS ONE N2 - Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. KW - age KW - observer agreement KW - prophylactic lithium KW - mapping susceptibility genes KW - mood disorders KW - onset KW - association KW - reliability KW - morality KW - illness Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130938 VL - 8 IS - 6 ER - TY - JOUR A1 - Temme, Fabian A1 - Adam, Jan A1 - Ahnen, Max L. A1 - Baack, Dominik A1 - Balbo, Matteo A1 - Bergmann, Matthias A1 - Biland, Adrian A1 - Blank, Michael A1 - Bretz, Thomas A1 - Brügge, Kai A. A1 - Buss, Jens A1 - Dmytriiev, Anton A1 - Dorner, Daniela A1 - Einecke, Sabrina A1 - Hempfling, Christina A1 - Hildebrand, Dorothee A1 - Hughes, Gareth A1 - Linhoff, Lena A1 - Mannheim, Karl A1 - Müller, Sebastian A1 - Neise, Dominik A1 - Neronov, Andrii A1 - Nöthe, Max A1 - Paravac, Aleksander A1 - Pauss, Felicitas A1 - Rhode, Wolfgang A1 - Shukla, Amit A1 - Thaele, Julia A1 - Walter, Roland T1 - Long-Term monitoring of bright blazars in the multi-GeV to TeV range with FACT JF - Galaxies N2 - Blazars like Markarian 421 or Markarian 501 are active galactic nuclei (AGN), with their jets orientated towards the observer. They are among the brightest objects in the very high energy (VHE) gamma ray regime (>100 GeV). Their emitted gamma-ray fluxes are extremely variable, with changing activity levels on timescales between minutes, months, and even years. Several questions are part of the current research, such as the question of the emission regions or the engine of the AGN and the particle acceleration. A dedicated longterm monitoring program is necessary to investigate the properties of blazars in detail. A densely sampled and unbiased light curve allows for observation of both high and low states of the sources, and the combination with multi-wavelength observation could contribute to the answer of several questions mentioned above. FACT (First G-APD Cherenkov Telescope) is the first operational telescope using silicon photomultiplier (SiPM, also known as Geigermode—Avalanche Photo Diode, G-APD) as photon detectors. SiPM have a very homogenous and stable longterm performance, and allow operation even during full moon without any filter, leading to a maximal duty cycle for an Imaging Air Cherenkov Telescope (IACT). Hence, FACT is an ideal device for such a longterm monitoring of bright blazars. A small set of sources (e.g., Markarian 421, Markarian 501, 1ES 1959+650, and 1ES 2344+51.4) is currently being monitored. In this contribution, the FACT telescope and the concept of longterm monitoring of bright blazars will be introduced. The results of the monitoring program will be shown, and the advantages of densely sampled and unbiased light curves will be discussed. KW - Imaging Air Cherenkov Telescope KW - First G-APD Cherenkov Telescope KW - very high energy gamma rays KW - long-term monitoring KW - silicon photo multiplier Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198088 SN - 2075-4434 VL - 5 IS - 1 PB - MDPI ER - TY - JOUR A1 - Herrmann, Johannes A1 - Adam, Elisabeth Hannah A1 - Notz, Quirin A1 - Helmer, Philipp A1 - Sonntagbauer, Michael A1 - Ungemach-Papenberg, Peter A1 - Sanns, Andreas A1 - Zausig, York A1 - Steinfeldt, Thorsten A1 - Torje, Iuliu A1 - Schmid, Benedikt A1 - Schlesinger, Tobias A1 - Rolfes, Caroline A1 - Reyher, Christian A1 - Kredel, Markus A1 - Stumpner, Jan A1 - Brack, Alexander A1 - Wurmb, Thomas A1 - Gill-Schuster, Daniel A1 - Kranke, Peter A1 - Weismann, Dirk A1 - Klinker, Hartwig A1 - Heuschmann, Peter A1 - Rücker, Viktoria A1 - Frantz, Stefan A1 - Ertl, Georg A1 - Muellenbach, Ralf Michael A1 - Mutlak, Haitham A1 - Meybohm, Patrick A1 - Zacharowski, Kai A1 - Lotz, Christopher T1 - COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study JF - Frontiers in Medicine N2 - Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients. KW - COVID-19 KW - ARDS (acute respiratory distress syndrome) KW - intensive care medicine KW - pandemia KW - Germany Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219834 SN - 2296-858X VL - 7 ER -