Feasibility study of using high-throughput drug sensitivity testing to target recurrent glioblastoma stem cells for individualized treatment
Identifieur interne : 000818 ( Main/Exploration ); précédent : 000817; suivant : 000819Feasibility study of using high-throughput drug sensitivity testing to target recurrent glioblastoma stem cells for individualized treatment
Auteurs : Erlend Skaga [Norvège] ; Evgeny Kulesskiy [Finlande] ; Marit Brynjulvsen [Norvège] ; Cecilie J. Sandberg [Norvège] ; Swapnil Potdar [Finlande] ; Iver A. Langmoen [Norvège] ; Aki Laakso [Finlande] ; Emília Gaál-Paavola [Finlande] ; Markus Perola [Finlande] ; Krister Wennerberg [Finlande] ; Einar O. Vik-Mo [Norvège]Source :
- Clinical and Translational Medicine [ 2001-1326 ] ; 2019.
Abstract
Despite the well described heterogeneity in glioblastoma (GBM), treatment is standardized, and clinical trials investigate treatment effects at population level. Genomics-driven oncology for stratified treatments allow clinical decision making in only a small minority of screened patients. Addressing tumor heterogeneity, we aimed to establish a clinical translational protocol in recurrent GBM (recGBM) utilizing autologous glioblastoma stem cell (GSC) cultures and automated high-throughput drug sensitivity and resistance testing (DSRT) for individualized treatment within the time available for clinical application.
From ten patients undergoing surgery for recGBM, we established individual cell cultures and characterized the GSCs by functional assays. 7/10 GSC cultures could be serially expanded. The individual GSCs displayed intertumoral differences in their proliferative capacity, expression of stem cell markers and variation in their in vitro and in vivo morphology. We defined a time frame of 10 weeks from surgery to complete the entire pre-clinical work-up; establish individualized GSC cultures, evaluate drug sensitivity patterns of 525 anticancer drugs, and identify options for individualized treatment. Within the time frame for clinical translation 5/7 cultures reached sufficient cell yield for complete drug screening. The DSRT revealed significant intertumoral heterogeneity to anticancer drugs (p < 0.0001). Using curated reference databases of drug sensitivity in GBM and healthy bone marrow cells, we identified individualized treatment options in all patients. Individualized treatment options could be selected from FDA-approved drugs from a variety of different drug classes in all cases.
In recGBM, GSC cultures could successfully be established in the majority of patients. The individual cultures displayed intertumoral heterogeneity in their in vitro and in vivo behavior. Within a time frame for clinical application, we could perform DSRT in 50% of recGBM patients. The DSRT revealed a remarkable intertumoral heterogeneity in sensitivity to anticancer drugs in recGBM that could allow tailored therapeutic options for functional precision medicine.
Url:
DOI: 10.1186/s40169-019-0253-6
PubMed: 31889236
PubMed Central: 6937360
Affiliations:
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Box 4950, Nydalen, 0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 4950, Nydalen, 0424 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8921</institution-id><institution-id institution-id-type="GRID">grid.5510.1</institution-id><institution>Institute of Clinical Medicine, Faculty of Medicine,</institution><institution>University of Oslo,</institution></institution-wrap>P.O. Box 1112, Blindern, 0317 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 1112, Blindern, 0317 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author><author><name sortKey="Kulesskiy, Evgeny" sort="Kulesskiy, Evgeny" uniqKey="Kulesskiy E" first="Evgeny" last="Kulesskiy">Evgeny Kulesskiy</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0410 2071</institution-id><institution-id institution-id-type="GRID">grid.7737.4</institution-id><institution>Institute for Molecular Medicine Finland, FIMM,</institution><institution>University of Helsinki,</institution></institution-wrap>Tukholmankatu 8, 00290 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Tukholmankatu 8, 00290 Helsinki</wicri:regionArea><wicri:noRegion>00290 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Brynjulvsen, Marit" sort="Brynjulvsen, Marit" uniqKey="Brynjulvsen M" first="Marit" last="Brynjulvsen">Marit Brynjulvsen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0389 8485</institution-id><institution-id institution-id-type="GRID">grid.55325.34</institution-id><institution>Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery,</institution><institution>Oslo University Hospital,</institution></institution-wrap>P.O. Box 4950, Nydalen, 0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 4950, Nydalen, 0424 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8921</institution-id><institution-id institution-id-type="GRID">grid.5510.1</institution-id><institution>Institute of Clinical Medicine, Faculty of Medicine,</institution><institution>University of Oslo,</institution></institution-wrap>P.O. Box 1112, Blindern, 0317 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 1112, Blindern, 0317 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author><author><name sortKey="Sandberg, Cecilie J" sort="Sandberg, Cecilie J" uniqKey="Sandberg C" first="Cecilie J." last="Sandberg">Cecilie J. Sandberg</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0389 8485</institution-id><institution-id institution-id-type="GRID">grid.55325.34</institution-id><institution>Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery,</institution><institution>Oslo University Hospital,</institution></institution-wrap>P.O. Box 4950, Nydalen, 0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 4950, Nydalen, 0424 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author><author><name sortKey="Potdar, Swapnil" sort="Potdar, Swapnil" uniqKey="Potdar S" first="Swapnil" last="Potdar">Swapnil Potdar</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0410 2071</institution-id><institution-id institution-id-type="GRID">grid.7737.4</institution-id><institution>Institute for Molecular Medicine Finland, FIMM,</institution><institution>University of Helsinki,</institution></institution-wrap>Tukholmankatu 8, 00290 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Tukholmankatu 8, 00290 Helsinki</wicri:regionArea><wicri:noRegion>00290 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Langmoen, Iver A" sort="Langmoen, Iver A" uniqKey="Langmoen I" first="Iver A." last="Langmoen">Iver A. Langmoen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0389 8485</institution-id><institution-id institution-id-type="GRID">grid.55325.34</institution-id><institution>Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery,</institution><institution>Oslo University Hospital,</institution></institution-wrap>P.O. Box 4950, Nydalen, 0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 4950, Nydalen, 0424 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8921</institution-id><institution-id institution-id-type="GRID">grid.5510.1</institution-id><institution>Institute of Clinical Medicine, Faculty of Medicine,</institution><institution>University of Oslo,</institution></institution-wrap>P.O. Box 1112, Blindern, 0317 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 1112, Blindern, 0317 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author><author><name sortKey="Laakso, Aki" sort="Laakso, Aki" uniqKey="Laakso A" first="Aki" last="Laakso">Aki Laakso</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0410 2071</institution-id><institution-id institution-id-type="GRID">grid.7737.4</institution-id><institution>Department of Neurosurgery, Helsinki University Hospital and Clinical Neurosciences,</institution><institution>University of Helsinki,</institution></institution-wrap>Topeliuksenkatu 5, 00260 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Topeliuksenkatu 5, 00260 Helsinki</wicri:regionArea><wicri:noRegion>00260 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Gaal Paavola, Emilia" sort="Gaal Paavola, Emilia" uniqKey="Gaal Paavola E" first="Emília" last="Gaál-Paavola">Emília Gaál-Paavola</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0410 2071</institution-id><institution-id institution-id-type="GRID">grid.7737.4</institution-id><institution>Department of Neurosurgery, Helsinki University Hospital and Clinical Neurosciences,</institution><institution>University of Helsinki,</institution></institution-wrap>Topeliuksenkatu 5, 00260 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Topeliuksenkatu 5, 00260 Helsinki</wicri:regionArea><wicri:noRegion>00260 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Perola, Markus" sort="Perola, Markus" uniqKey="Perola M" first="Markus" last="Perola">Markus Perola</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0410 2071</institution-id><institution-id institution-id-type="GRID">grid.7737.4</institution-id><institution>Institute for Molecular Medicine Finland, FIMM,</institution><institution>University of Helsinki,</institution></institution-wrap>Tukholmankatu 8, 00290 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Tukholmankatu 8, 00290 Helsinki</wicri:regionArea><wicri:noRegion>00290 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Wennerberg, Krister" sort="Wennerberg, Krister" uniqKey="Wennerberg K" first="Krister" last="Wennerberg">Krister Wennerberg</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0410 2071</institution-id><institution-id institution-id-type="GRID">grid.7737.4</institution-id><institution>Institute for Molecular Medicine Finland, FIMM,</institution><institution>University of Helsinki,</institution></institution-wrap>Tukholmankatu 8, 00290 Helsinki, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Tukholmankatu 8, 00290 Helsinki</wicri:regionArea><wicri:noRegion>00290 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Vik Mo, Einar O" sort="Vik Mo, Einar O" uniqKey="Vik Mo E" first="Einar O." last="Vik-Mo">Einar O. Vik-Mo</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0389 8485</institution-id><institution-id institution-id-type="GRID">grid.55325.34</institution-id><institution>Vilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research and Department of Neurosurgery,</institution><institution>Oslo University Hospital,</institution></institution-wrap>P.O. Box 4950, Nydalen, 0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 4950, Nydalen, 0424 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8921</institution-id><institution-id institution-id-type="GRID">grid.5510.1</institution-id><institution>Institute of Clinical Medicine, Faculty of Medicine,</institution><institution>University of Oslo,</institution></institution-wrap>P.O. Box 1112, Blindern, 0317 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>P.O. Box 1112, Blindern, 0317 Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author></analytic><series><title level="j">Clinical and Translational Medicine</title><idno type="eISSN">2001-1326</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p id="Par1">Despite the well described heterogeneity in glioblastoma (GBM), treatment is standardized, and clinical trials investigate treatment effects at population level. Genomics-driven oncology for stratified treatments allow clinical decision making in only a small minority of screened patients. Addressing tumor heterogeneity, we aimed to establish a clinical translational protocol in recurrent GBM (recGBM) utilizing autologous glioblastoma stem cell (GSC) cultures and automated high-throughput drug sensitivity and resistance testing (DSRT) for individualized treatment within the time available for clinical application.</p></sec><sec><title>Results</title><p id="Par2">From ten patients undergoing surgery for recGBM, we established individual cell cultures and characterized the GSCs by functional assays. 7/10 GSC cultures could be serially expanded. The individual GSCs displayed intertumoral differences in their proliferative capacity, expression of stem cell markers and variation in their in vitro and in vivo morphology. We defined a time frame of 10 weeks from surgery to complete the entire pre-clinical work-up; establish individualized GSC cultures, evaluate drug sensitivity patterns of 525 anticancer drugs, and identify options for individualized treatment. Within the time frame for clinical translation 5/7 cultures reached sufficient cell yield for complete drug screening. The DSRT revealed significant intertumoral heterogeneity to anticancer drugs (p < 0.0001). Using curated reference databases of drug sensitivity in GBM and healthy bone marrow cells, we identified individualized treatment options in all patients. Individualized treatment options could be selected from FDA-approved drugs from a variety of different drug classes in all cases.</p></sec><sec><title>Conclusions</title><p id="Par3">In recGBM, GSC cultures could successfully be established in the majority of patients. The individual cultures displayed intertumoral heterogeneity in their in vitro and in vivo behavior. Within a time frame for clinical application, we could perform DSRT in 50% of recGBM patients. The DSRT revealed a remarkable intertumoral heterogeneity in sensitivity to anticancer drugs in recGBM that could allow tailored therapeutic options for functional precision medicine.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Stupp, R" uniqKey="Stupp R">R Stupp</name></author><author><name sortKey="Mason, Wp" uniqKey="Mason W">WP Mason</name></author><author><name sortKey="Van Den Bent, Mj" uniqKey="Van Den Bent M">MJ van den Bent</name></author><author><name sortKey="Michael, Wm" uniqKey="Michael W">WM Michael</name></author><author><name sortKey="Fisher, B" uniqKey="Fisher B">B Fisher</name></author><author><name sortKey="Taphoorn, Mj" uniqKey="Taphoorn M">MJ Taphoorn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ringel, F" uniqKey="Ringel F">F Ringel</name></author><author><name sortKey="Pape, H" uniqKey="Pape H">H Pape</name></author><author><name sortKey="Sabel, M" uniqKey="Sabel M">M Sabel</name></author><author><name sortKey="Krex, D" uniqKey="Krex D">D Krex</name></author><author><name sortKey="Bock, H" uniqKey="Bock H">H Bock</name></author><author><name sortKey="Misch, M" uniqKey="Misch M">M Misch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weller, M" uniqKey="Weller M">M Weller</name></author><author><name sortKey="Van Den Bent, M" uniqKey="Van Den Bent M">M van den Bent</name></author><author><name sortKey="Tonn, Jc" uniqKey="Tonn J">JC Tonn</name></author><author><name sortKey="Stupp, R" uniqKey="Stupp R">R Stupp</name></author><author><name sortKey="Preusser, M" uniqKey="Preusser M">M Preusser</name></author><author><name sortKey="Cohen Jonathan Moyal, E" uniqKey="Cohen Jonathan Moyal E">E Cohen-Jonathan-Moyal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nava, F" uniqKey="Nava F">F Nava</name></author><author><name sortKey="Tramacere, I" uniqKey="Tramacere I">I Tramacere</name></author><author><name sortKey="Fittipaldo, A" uniqKey="Fittipaldo A">A Fittipaldo</name></author><author><name sortKey="Bruzzone, M" uniqKey="Bruzzone M">M Bruzzone</name></author><author><name sortKey="Dimeco, F" uniqKey="Dimeco F">F Dimeco</name></author><author><name sortKey="Fariselli, L" uniqKey="Fariselli L">L Fariselli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suchorska, B" uniqKey="Suchorska B">B Suchorska</name></author><author><name sortKey="Weller, M" uniqKey="Weller M">M Weller</name></author><author><name sortKey="Tabatabai, G" uniqKey="Tabatabai G">G Tabatabai</name></author><author><name sortKey="Senft, C" uniqKey="Senft C">C Senft</name></author><author><name sortKey="Hau, P" uniqKey="Hau P">P Hau</name></author><author><name sortKey="Sabel, Mc" uniqKey="Sabel M">MC Sabel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vik Mo, E" uniqKey="Vik Mo E">E Vik-Mo</name></author><author><name sortKey="Sandberg, C" uniqKey="Sandberg C">C Sandberg</name></author><author><name sortKey="Olstorn, H" uniqKey="Olstorn H">H Olstorn</name></author><author><name sortKey="Varghese, M" uniqKey="Varghese M">M Varghese</name></author><author><name sortKey="Brandal, P" uniqKey="Brandal P">P Brandal</name></author><author><name sortKey="Ramm Pettersen, J" uniqKey="Ramm Pettersen J">J Ramm-Pettersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vik Mo, E" uniqKey="Vik Mo E">E Vik-Mo</name></author><author><name sortKey="Nyakas, M" uniqKey="Nyakas M">M Nyakas</name></author><author><name sortKey="Mikkelsen, B" uniqKey="Mikkelsen B">B Mikkelsen</name></author><author><name sortKey="Moe, M" uniqKey="Moe M">M Moe</name></author><author><name sortKey="Due T Nnesen, P" uniqKey="Due T Nnesen P">P Due-Tønnesen</name></author><author><name sortKey="Suso, E" uniqKey="Suso E">E Suso</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Joo, K" uniqKey="Joo K">K Joo</name></author><author><name sortKey="Kim, J" uniqKey="Kim J">J Kim</name></author><author><name sortKey="Jin, J" uniqKey="Jin J">J Jin</name></author><author><name sortKey="Kim, M" uniqKey="Kim M">M Kim</name></author><author><name sortKey="Seol, H" uniqKey="Seol H">H Seol</name></author><author><name sortKey="Muradov, J" uniqKey="Muradov J">J Muradov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lan, X" uniqKey="Lan X">X Lan</name></author><author><name sortKey="Jorg, Dj" uniqKey="Jorg D">DJ Jörg</name></author><author><name sortKey="Cavalli, Fm" uniqKey="Cavalli F">FM Cavalli</name></author><author><name sortKey="Richards, Lm" uniqKey="Richards L">LM Richards</name></author><author><name sortKey="Nguyen, Lv" uniqKey="Nguyen L">LV Nguyen</name></author><author><name sortKey="Vanner, Rj" uniqKey="Vanner R">RJ Vanner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Campos, B" uniqKey="Campos B">B Campos</name></author><author><name sortKey="Olsen, L" uniqKey="Olsen L">L Olsen</name></author><author><name sortKey="Urup, T" uniqKey="Urup T">T Urup</name></author><author><name sortKey="Poulsen, H" uniqKey="Poulsen H">H Poulsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sottoriva, A" uniqKey="Sottoriva A">A Sottoriva</name></author><author><name sortKey="Spiteri, I" uniqKey="Spiteri I">I Spiteri</name></author><author><name sortKey="Piccirillo, Sg" uniqKey="Piccirillo S">SG Piccirillo</name></author><author><name sortKey="Touloumis, A" uniqKey="Touloumis A">A Touloumis</name></author><author><name sortKey="Collins, Pv" uniqKey="Collins P">PV Collins</name></author><author><name sortKey="Marioni, Jc" uniqKey="Marioni J">JC Marioni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Patel, Ap" uniqKey="Patel A">AP Patel</name></author><author><name sortKey="Tirosh, I" uniqKey="Tirosh I">I Tirosh</name></author><author><name sortKey="Trombetta, Jj" uniqKey="Trombetta J">JJ Trombetta</name></author><author><name sortKey="Shalek, Ak" uniqKey="Shalek A">AK Shalek</name></author><author><name sortKey="Gillespie, Sm" uniqKey="Gillespie S">SM Gillespie</name></author><author><name sortKey="Wakimoto, H" uniqKey="Wakimoto H">H Wakimoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skaga, E" uniqKey="Skaga E">E Skaga</name></author><author><name sortKey="Kulesskiy, E" uniqKey="Kulesskiy E">E Kulesskiy</name></author><author><name sortKey="Fayzullin, A" uniqKey="Fayzullin A">A Fayzullin</name></author><author><name sortKey="Sandberg, Cj" uniqKey="Sandberg C">CJ Sandberg</name></author><author><name sortKey="Potdar, S" uniqKey="Potdar S">S Potdar</name></author><author><name sortKey="Kytt L, A" uniqKey="Kytt L A">A Kyttälä</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neftel, C" uniqKey="Neftel C">C Neftel</name></author><author><name sortKey="Laffy, J" uniqKey="Laffy J">J Laffy</name></author><author><name sortKey="Filbin, Mg" uniqKey="Filbin M">MG Filbin</name></author><author><name sortKey="Hara, T" uniqKey="Hara T">T Hara</name></author><author><name sortKey="Shore, Me" uniqKey="Shore M">ME Shore</name></author><author><name sortKey="Rahme, Gj" uniqKey="Rahme G">GJ Rahme</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author><author><name sortKey="Cazzato, E" uniqKey="Cazzato E">E Cazzato</name></author><author><name sortKey="Ladewig, E" uniqKey="Ladewig E">E Ladewig</name></author><author><name sortKey="Frattini, V" uniqKey="Frattini V">V Frattini</name></author><author><name sortKey="Rosenbloom, Di" uniqKey="Rosenbloom D">DI Rosenbloom</name></author><author><name sortKey="Zairis, S" uniqKey="Zairis S">S Zairis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, H" uniqKey="Kim H">H Kim</name></author><author><name sortKey="Zheng, S" uniqKey="Zheng S">S Zheng</name></author><author><name sortKey="Amini, Ss" uniqKey="Amini S">SS Amini</name></author><author><name sortKey="Virk, Sm" uniqKey="Virk S">SM Virk</name></author><author><name sortKey="Mikkelsen, T" uniqKey="Mikkelsen T">T Mikkelsen</name></author><author><name sortKey="Brat, Dj" uniqKey="Brat D">DJ Brat</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, J" uniqKey="Kim J">J Kim</name></author><author><name sortKey="Lee, I H" uniqKey="Lee I">I-H Lee</name></author><author><name sortKey="Cho, H" uniqKey="Cho H">H Cho</name></author><author><name sortKey="Park, C K" uniqKey="Park C">C-K Park</name></author><author><name sortKey="Jung, Y S" uniqKey="Jung Y">Y-S Jung</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sch Fer, N" uniqKey="Sch Fer N">N Schäfer</name></author><author><name sortKey="Gielen, Gh" uniqKey="Gielen G">GH Gielen</name></author><author><name sortKey="Rauschenbach, L" uniqKey="Rauschenbach L">L Rauschenbach</name></author><author><name sortKey="Kebir, S" uniqKey="Kebir S">S Kebir</name></author><author><name sortKey="Till, A" uniqKey="Till A">A Till</name></author><author><name sortKey="Reinartz, R" uniqKey="Reinartz R">R Reinartz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hunter, C" uniqKey="Hunter C">C Hunter</name></author><author><name sortKey="Smith, R" uniqKey="Smith R">R Smith</name></author><author><name sortKey="Cahill, Dp" uniqKey="Cahill D">DP Cahill</name></author><author><name sortKey="Stephens, P" uniqKey="Stephens P">P Stephens</name></author><author><name sortKey="Stevens, C" uniqKey="Stevens C">C Stevens</name></author><author><name sortKey="Teague, J" uniqKey="Teague J">J Teague</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Be" uniqKey="Johnson B">BE Johnson</name></author><author><name sortKey="Mazor, T" uniqKey="Mazor T">T Mazor</name></author><author><name sortKey="Hong, C" uniqKey="Hong C">C Hong</name></author><author><name sortKey="Barnes, M" uniqKey="Barnes M">M Barnes</name></author><author><name sortKey="Aihara, K" uniqKey="Aihara K">K Aihara</name></author><author><name sortKey="Mclean, Cy" uniqKey="Mclean C">CY McLean</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stupp, R" uniqKey="Stupp R">R Stupp</name></author><author><name sortKey="Taillibert, S" uniqKey="Taillibert S">S Taillibert</name></author><author><name sortKey="Kanner, A" uniqKey="Kanner A">A Kanner</name></author><author><name sortKey="Read, W" uniqKey="Read W">W Read</name></author><author><name sortKey="Einberg, D" uniqKey="Einberg D">D Einberg</name></author><author><name sortKey="Lhermitte, B" uniqKey="Lhermitte B">B Lhermitte</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weller, M" uniqKey="Weller M">M Weller</name></author><author><name sortKey="Butowski, N" uniqKey="Butowski N">N Butowski</name></author><author><name sortKey="Tran, Dd" uniqKey="Tran D">DD Tran</name></author><author><name sortKey="Recht, Ld" uniqKey="Recht L">LD Recht</name></author><author><name sortKey="Lim, M" uniqKey="Lim M">M Lim</name></author><author><name sortKey="Hirte, H" uniqKey="Hirte H">H Hirte</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stupp, R" uniqKey="Stupp R">R Stupp</name></author><author><name sortKey="Hegi, Me" uniqKey="Hegi M">ME Hegi</name></author><author><name sortKey="Gorlia, T" uniqKey="Gorlia T">T Gorlia</name></author><author><name sortKey="Erridge, Sc" uniqKey="Erridge S">SC Erridge</name></author><author><name sortKey="Perry, J" uniqKey="Perry J">J Perry</name></author><author><name sortKey="Hong, Y K" uniqKey="Hong Y">Y-K Hong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karajannis, Ma" uniqKey="Karajannis M">MA Karajannis</name></author><author><name sortKey="Legault, G" uniqKey="Legault G">G Legault</name></author><author><name sortKey="Fisher, Mj" uniqKey="Fisher M">MJ Fisher</name></author><author><name sortKey="Milla, Ss" uniqKey="Milla S">SS Milla</name></author><author><name sortKey="Cohen, Kj" uniqKey="Cohen K">KJ Cohen</name></author><author><name sortKey="Wisoff, Jh" uniqKey="Wisoff J">JH Wisoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tourneau, C" uniqKey="Tourneau C">C Tourneau</name></author><author><name sortKey="Delord, J P" uniqKey="Delord J">J-P Delord</name></author><author><name sortKey="Goncalves, A" uniqKey="Goncalves A">A Gonçalves</name></author><author><name sortKey="Gavoille, C" uniqKey="Gavoille C">C Gavoille</name></author><author><name sortKey="Dubot, C" uniqKey="Dubot C">C Dubot</name></author><author><name sortKey="Isambert, N" uniqKey="Isambert N">N Isambert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marquart, J" uniqKey="Marquart J">J Marquart</name></author><author><name sortKey="Chen, Ey" uniqKey="Chen E">EY Chen</name></author><author><name sortKey="Prasad, V" uniqKey="Prasad V">V Prasad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pemovska, T" uniqKey="Pemovska T">T Pemovska</name></author><author><name sortKey="Kontro, M" uniqKey="Kontro M">M Kontro</name></author><author><name sortKey="Yadav, B" uniqKey="Yadav B">B Yadav</name></author><author><name sortKey="Edgren, H" uniqKey="Edgren H">H Edgren</name></author><author><name sortKey="Eldfors, S" uniqKey="Eldfors S">S Eldfors</name></author><author><name sortKey="Szwajda, A" uniqKey="Szwajda A">A Szwajda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pauli, C" uniqKey="Pauli C">C Pauli</name></author><author><name sortKey="Hopkins, Bd" uniqKey="Hopkins B">BD Hopkins</name></author><author><name sortKey="Prandi, D" uniqKey="Prandi D">D Prandi</name></author><author><name sortKey="Shaw, R" uniqKey="Shaw R">R Shaw</name></author><author><name sortKey="Fedrizzi, T" uniqKey="Fedrizzi T">T Fedrizzi</name></author><author><name sortKey="Sboner, A" uniqKey="Sboner A">A Sboner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oppenlander, Me" uniqKey="Oppenlander M">ME Oppenlander</name></author><author><name sortKey="Wolf, Ab" uniqKey="Wolf A">AB Wolf</name></author><author><name sortKey="Snyder, La" uniqKey="Snyder L">LA Snyder</name></author><author><name sortKey="Bina, R" uniqKey="Bina R">R Bina</name></author><author><name sortKey="Wilson, Jr" uniqKey="Wilson J">JR Wilson</name></author><author><name sortKey="Coons, Sw" uniqKey="Coons S">SW Coons</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sughrue, Me" uniqKey="Sughrue M">ME Sughrue</name></author><author><name sortKey="Sheean, T" uniqKey="Sheean T">T Sheean</name></author><author><name sortKey="Bonney, Pa" uniqKey="Bonney P">PA Bonney</name></author><author><name sortKey="Maurer, Aj" uniqKey="Maurer A">AJ Maurer</name></author><author><name sortKey="Teo, C" uniqKey="Teo C">C Teo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yadav, B" uniqKey="Yadav B">B Yadav</name></author><author><name sortKey="Pemovska, T" uniqKey="Pemovska T">T Pemovska</name></author><author><name sortKey="Szwajda, A" uniqKey="Szwajda A">A Szwajda</name></author><author><name sortKey="Kulesskiy, E" uniqKey="Kulesskiy E">E Kulesskiy</name></author><author><name sortKey="Kontro, M" uniqKey="Kontro M">M Kontro</name></author><author><name sortKey="Karjalainen, R" uniqKey="Karjalainen R">R Karjalainen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brodin, Ba" uniqKey="Brodin B">BA Brodin</name></author><author><name sortKey="Wennerberg, K" uniqKey="Wennerberg K">K Wennerberg</name></author><author><name sortKey="Lidbrink, E" uniqKey="Lidbrink E">E Lidbrink</name></author><author><name sortKey="Brosjo, O" uniqKey="Brosjo O">O Brosjö</name></author><author><name sortKey="Potdar, S" uniqKey="Potdar S">S Potdar</name></author><author><name sortKey="Wilson, Jn" uniqKey="Wilson J">JN Wilson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ostermann, S" uniqKey="Ostermann S">S Ostermann</name></author><author><name sortKey="Csajka, C" uniqKey="Csajka C">C Csajka</name></author><author><name sortKey="Buclin, T" uniqKey="Buclin T">T Buclin</name></author><author><name sortKey="Leyvraz, S" uniqKey="Leyvraz S">S Leyvraz</name></author><author><name sortKey="Lejeune, F" uniqKey="Lejeune F">F Lejeune</name></author><author><name sortKey="Decosterd, La" uniqKey="Decosterd L">LA Decosterd</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skaga, E" uniqKey="Skaga E">E Skaga</name></author><author><name sortKey="Skaga, I" uniqKey="Skaga I">I Skaga</name></author><author><name sortKey="Grieg, Z" uniqKey="Grieg Z">Z Grieg</name></author><author><name sortKey="Sandberg, Cj" uniqKey="Sandberg C">CJ Sandberg</name></author><author><name sortKey="Langmoen, Ia" uniqKey="Langmoen I">IA Langmoen</name></author><author><name sortKey="Vik Mo, Eo" uniqKey="Vik Mo E">EO Vik-Mo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lun, X" uniqKey="Lun X">X Lun</name></author><author><name sortKey="Wells, Cj" uniqKey="Wells C">CJ Wells</name></author><author><name sortKey="Grinshtein, N" uniqKey="Grinshtein N">N Grinshtein</name></author><author><name sortKey="King, Jc" uniqKey="King J">JC King</name></author><author><name sortKey="Hao, X" uniqKey="Hao X">X Hao</name></author><author><name sortKey="Dang, N H" uniqKey="Dang N">N-H Dang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stensj En, A" uniqKey="Stensj En A">A Stensjøen</name></author><author><name sortKey="Solheim, O" uniqKey="Solheim O">O Solheim</name></author><author><name sortKey="Kvistad, K" uniqKey="Kvistad K">K Kvistad</name></author><author><name sortKey="H Berg, Ak" uniqKey="H Berg A">AK Håberg</name></author><author><name sortKey="Salvesen, " uniqKey="Salvesen ">Ø Salvesen</name></author><author><name sortKey="Berntsen, E" uniqKey="Berntsen E">E Berntsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hegi, Me" uniqKey="Hegi M">ME Hegi</name></author><author><name sortKey="Diserens, A C" uniqKey="Diserens A">A-C Diserens</name></author><author><name sortKey="Gorlia, T" uniqKey="Gorlia T">T Gorlia</name></author><author><name sortKey="Hamou, M F" uniqKey="Hamou M">M-F Hamou</name></author><author><name sortKey="De Tribolet, N" uniqKey="De Tribolet N">N de Tribolet</name></author><author><name sortKey="Weller, M" uniqKey="Weller M">M Weller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="D Lessandris, Q" uniqKey="D Lessandris Q">Q D’Alessandris</name></author><author><name sortKey="Biffoni, M" uniqKey="Biffoni M">M Biffoni</name></author><author><name sortKey="Martini, M" uniqKey="Martini M">M Martini</name></author><author><name sortKey="Runci, D" uniqKey="Runci D">D Runci</name></author><author><name sortKey="Buccarelli, M" uniqKey="Buccarelli M">M Buccarelli</name></author><author><name sortKey="Cenci, T" uniqKey="Cenci T">T Cenci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lamborn, Kr" uniqKey="Lamborn K">KR Lamborn</name></author><author><name sortKey="Yung, Aw" uniqKey="Yung A">AW Yung</name></author><author><name sortKey="Chang, Sm" uniqKey="Chang S">SM Chang</name></author><author><name sortKey="Wen, Py" uniqKey="Wen P">PY Wen</name></author><author><name sortKey="Cloughesy, Tf" uniqKey="Cloughesy T">TF Cloughesy</name></author><author><name sortKey="Angelis, L" uniqKey="Angelis L">L Angelis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vredenburgh, Jj" uniqKey="Vredenburgh J">JJ Vredenburgh</name></author><author><name sortKey="Desjardins, A" uniqKey="Desjardins A">A Desjardins</name></author><author><name sortKey="Reardon, Da" uniqKey="Reardon D">DA Reardon</name></author><author><name sortKey="Friedman, Hs" uniqKey="Friedman H">HS Friedman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bruce, Jn" uniqKey="Bruce J">JN Bruce</name></author><author><name sortKey="Fine, Rl" uniqKey="Fine R">RL Fine</name></author><author><name sortKey="Canoll, P" uniqKey="Canoll P">P Canoll</name></author><author><name sortKey="Yun, J" uniqKey="Yun J">J Yun</name></author><author><name sortKey="Kennedy, Bc" uniqKey="Kennedy B">BC Kennedy</name></author><author><name sortKey="Rosenfeld, Ss" uniqKey="Rosenfeld S">SS Rosenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamer, Pc" uniqKey="Hamer P">PC Hamer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alshami, J" uniqKey="Alshami J">J Alshami</name></author><author><name sortKey="Guiot, M C" uniqKey="Guiot M">M-C Guiot</name></author><author><name sortKey="Owen, S" uniqKey="Owen S">S Owen</name></author><author><name sortKey="Kavan, P" uniqKey="Kavan P">P Kavan</name></author><author><name sortKey="Gibson, N" uniqKey="Gibson N">N Gibson</name></author><author><name sortKey="Solca, F" uniqKey="Solca F">F Solca</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brandes, A" uniqKey="Brandes A">A Brandes</name></author><author><name sortKey="Ermani, M" uniqKey="Ermani M">M Ermani</name></author><author><name sortKey="Turazzi, S" uniqKey="Turazzi S">S Turazzi</name></author><author><name sortKey="Scelzi, E" uniqKey="Scelzi E">E Scelzi</name></author><author><name sortKey="Berti, F" uniqKey="Berti F">F Berti</name></author><author><name sortKey="Amista, P" uniqKey="Amista P">P Amistà</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, P" uniqKey="Tang P">P Tang</name></author><author><name sortKey="Roldan, G" uniqKey="Roldan G">G Roldan</name></author><author><name sortKey="Brasher, P" uniqKey="Brasher P">P Brasher</name></author><author><name sortKey="Fulton, D" uniqKey="Fulton D">D Fulton</name></author><author><name sortKey="Roa, W" uniqKey="Roa W">W Roa</name></author><author><name sortKey="Murtha, A" uniqKey="Murtha A">A Murtha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Touat, M" uniqKey="Touat M">M Touat</name></author><author><name sortKey="Idbaih, A" uniqKey="Idbaih A">A Idbaih</name></author><author><name sortKey="Sanson, M" uniqKey="Sanson M">M Sanson</name></author><author><name sortKey="Ligon, K" uniqKey="Ligon K">K Ligon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, P" uniqKey="Yang P">P Yang</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W Zhang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Peng, X" uniqKey="Peng X">X Peng</name></author><author><name sortKey="Chen, B" uniqKey="Chen B">B Chen</name></author><author><name sortKey="Qiu, X" uniqKey="Qiu X">X Qiu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stupp, R" uniqKey="Stupp R">R Stupp</name></author><author><name sortKey="Hegi, Me" uniqKey="Hegi M">ME Hegi</name></author><author><name sortKey="Mason, Wp" uniqKey="Mason W">WP Mason</name></author><author><name sortKey="Van Den Bent, Mj" uniqKey="Van Den Bent M">MJ van den Bent</name></author><author><name sortKey="Taphoorn, Mj" uniqKey="Taphoorn M">MJ Taphoorn</name></author><author><name sortKey="Janzer, Rc" uniqKey="Janzer R">RC Janzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pitz, Mw" uniqKey="Pitz M">MW Pitz</name></author><author><name sortKey="Desai, A" uniqKey="Desai A">A Desai</name></author><author><name sortKey="Grossman, Sa" uniqKey="Grossman S">SA Grossman</name></author><author><name sortKey="Blakeley, Jo" uniqKey="Blakeley J">JO Blakeley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacus, Mo" uniqKey="Jacus M">MO Jacus</name></author><author><name sortKey="Daryani, V" uniqKey="Daryani V">V Daryani</name></author><author><name sortKey="Harstead, Ek" uniqKey="Harstead E">EK Harstead</name></author><author><name sortKey="Patel, Yt" uniqKey="Patel Y">YT Patel</name></author><author><name sortKey="Throm, Sl" uniqKey="Throm S">SL Throm</name></author><author><name sortKey="Stewart, Cf" uniqKey="Stewart C">CF Stewart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levy, Jm" uniqKey="Levy J">JM Levy</name></author><author><name sortKey="Zahedi, S" uniqKey="Zahedi S">S Zahedi</name></author><author><name sortKey="Griesinger, Am" uniqKey="Griesinger A">AM Griesinger</name></author><author><name sortKey="Morin, A" uniqKey="Morin A">A Morin</name></author><author><name sortKey="Davies, Kd" uniqKey="Davies K">KD Davies</name></author><author><name sortKey="Aisner, Dl" uniqKey="Aisner D">DL Aisner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reungwetwattana, T" uniqKey="Reungwetwattana T">T Reungwetwattana</name></author><author><name sortKey="Nakagawa, K" uniqKey="Nakagawa K">K Nakagawa</name></author><author><name sortKey="Cho, B" uniqKey="Cho B">B Cho</name></author><author><name sortKey="Cobo, M" uniqKey="Cobo M">M Cobo</name></author><author><name sortKey="Cho, E" uniqKey="Cho E">E Cho</name></author><author><name sortKey="Bertolini, A" uniqKey="Bertolini A">A Bertolini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davies, Ma" uniqKey="Davies M">MA Davies</name></author><author><name sortKey="Philippe, Sm" uniqKey="Philippe S">SM Philippe</name></author><author><name sortKey="Caroline, Rm" uniqKey="Caroline R">RM Caroline</name></author><author><name sortKey="Jean Jacques, Gm" uniqKey="Jean Jacques G">GM Jean-Jacques</name></author><author><name sortKey="Keith, Ft" uniqKey="Keith F">FT Keith</name></author><author><name sortKey="Ana" uniqKey="Ana">Ana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bobillo, S" uniqKey="Bobillo S">S Bobillo</name></author><author><name sortKey="Abrisqueta, P" uniqKey="Abrisqueta P">P Abrisqueta</name></author><author><name sortKey="Carpio, C" uniqKey="Carpio C">C Carpio</name></author><author><name sortKey="Raheja, P" uniqKey="Raheja P">P Raheja</name></author><author><name sortKey="Castellvi, J" uniqKey="Castellvi J">J Castellví</name></author><author><name sortKey="Crespo, M" uniqKey="Crespo M">M Crespo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Warren, K" uniqKey="Warren K">K Warren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qazi, M" uniqKey="Qazi M">M Qazi</name></author><author><name sortKey="Vora, P" uniqKey="Vora P">P Vora</name></author><author><name sortKey="Venugopal, C" uniqKey="Venugopal C">C Venugopal</name></author><author><name sortKey="Sidhu, S" uniqKey="Sidhu S">S Sidhu</name></author><author><name sortKey="Moffat, J" uniqKey="Moffat J">J Moffat</name></author><author><name sortKey="Swanton, C" uniqKey="Swanton C">C Swanton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vivanco, I" uniqKey="Vivanco I">I Vivanco</name></author><author><name sortKey="Robins, Ih" uniqKey="Robins I">IH Robins</name></author><author><name sortKey="Rohle, D" uniqKey="Rohle D">D Rohle</name></author><author><name sortKey="Campos, C" uniqKey="Campos C">C Campos</name></author><author><name sortKey="Grommes, C" uniqKey="Grommes C">C Grommes</name></author><author><name sortKey="Nghiemphu, P" uniqKey="Nghiemphu P">P Nghiemphu</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Finlande</li><li>Norvège</li></country><region><li>Østlandet</li></region><settlement><li>Oslo</li></settlement></list><tree><country name="Norvège"><region name="Østlandet"><name sortKey="Skaga, Erlend" sort="Skaga, Erlend" uniqKey="Skaga E" first="Erlend" last="Skaga">Erlend Skaga</name></region><name sortKey="Brynjulvsen, Marit" sort="Brynjulvsen, Marit" uniqKey="Brynjulvsen M" first="Marit" last="Brynjulvsen">Marit Brynjulvsen</name><name sortKey="Brynjulvsen, Marit" sort="Brynjulvsen, Marit" uniqKey="Brynjulvsen M" first="Marit" last="Brynjulvsen">Marit Brynjulvsen</name><name sortKey="Langmoen, Iver A" sort="Langmoen, Iver A" uniqKey="Langmoen I" first="Iver A." last="Langmoen">Iver A. Langmoen</name><name sortKey="Langmoen, Iver A" sort="Langmoen, Iver A" uniqKey="Langmoen I" first="Iver A." last="Langmoen">Iver A. Langmoen</name><name sortKey="Sandberg, Cecilie J" sort="Sandberg, Cecilie J" uniqKey="Sandberg C" first="Cecilie J." last="Sandberg">Cecilie J. Sandberg</name><name sortKey="Skaga, Erlend" sort="Skaga, Erlend" uniqKey="Skaga E" first="Erlend" last="Skaga">Erlend Skaga</name><name sortKey="Vik Mo, Einar O" sort="Vik Mo, Einar O" uniqKey="Vik Mo E" first="Einar O." last="Vik-Mo">Einar O. Vik-Mo</name><name sortKey="Vik Mo, Einar O" sort="Vik Mo, Einar O" uniqKey="Vik Mo E" first="Einar O." last="Vik-Mo">Einar O. Vik-Mo</name></country><country name="Finlande"><noRegion><name sortKey="Kulesskiy, Evgeny" sort="Kulesskiy, Evgeny" uniqKey="Kulesskiy E" first="Evgeny" last="Kulesskiy">Evgeny Kulesskiy</name></noRegion><name sortKey="Gaal Paavola, Emilia" sort="Gaal Paavola, Emilia" uniqKey="Gaal Paavola E" first="Emília" last="Gaál-Paavola">Emília Gaál-Paavola</name><name sortKey="Laakso, Aki" sort="Laakso, Aki" uniqKey="Laakso A" first="Aki" last="Laakso">Aki Laakso</name><name sortKey="Perola, Markus" sort="Perola, Markus" uniqKey="Perola M" first="Markus" last="Perola">Markus Perola</name><name sortKey="Potdar, Swapnil" sort="Potdar, Swapnil" uniqKey="Potdar S" first="Swapnil" last="Potdar">Swapnil Potdar</name><name sortKey="Wennerberg, Krister" sort="Wennerberg, Krister" uniqKey="Wennerberg K" first="Krister" last="Wennerberg">Krister Wennerberg</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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