Artificial intelligence extension of the OSCAR-IB criteria

Artificial intelligence (AI)-based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human-led validated consensus quality control criteria (OSCAR-IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI-based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five-point expansion of the OSCAR-IB criteria to embrace AI (OSCAR-AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Artificial intelligence extension of the OSCAR-IB criteria

Artificial intelligence (AI)-based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human-led validated consensus quality control criteria (OSCAR-IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI-based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five-point expansion of the OSCAR-IB criteria to embrace AI (OSCAR-AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines

Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. / Methods: SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18–65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5–6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29). / Findings: From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15–27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81–2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (<1%) person died in the MD1003 group and there were no deaths in the placebo group. Despite use of mitigation strategies, MD1003 led to inaccurate laboratory results for tests using biotinylated antibodies. / Interpretation: This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis. / Funding: MedDay Pharmaceuticals

Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. Methods: SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18–65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5–6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29). Findings: From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15–27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81–2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (&lt;1%) person died in the MD1003 group and there were no deaths in the placebo group. Despite use of mitigation strategies, MD1003 led to inaccurate laboratory results for tests using biotinylated antibodies. Interpretation: This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis. Funding: MedDay Pharmaceuticals

Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial

Background There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. Methods SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18–65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5–6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov ( NCT02936037) and the EudraCT database (2016-000700-29). Findings From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15–27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81–2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (<1%) person died in the MD1003 group and there were no deaths in the placebo group. Despite use of mitigation strategies, MD1003 led to inaccurate laboratory results for tests using biotinylated antibodies. Interpretation This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis

Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

reserved328Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS.Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18-60 years) with SPMS and an Expanded Disability Status Scale score of 3.0-6.5 were randomly assigned (2: 1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials. gov, number NCT01665144.Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16.8 years (SD 8.3), and the mean time since conversion to SPMS was 3.8 years (SD 3.5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0.79, 95% CI 0.65-0.95; relative risk reduction 21%; p=0.013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups.Interpretation Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS.mixedKappos L.; Bar-Or A.; Cree B.A.C.; Fox R.J.; Giovannoni G.; Gold R.; Vermersch P.; Arnold D.L.; Arnould S.; Scherz T.; Wolf C.; Wallstrom E.; Dahlke F.; Achiron A.; Achtnichts L.; Agan K.; Akman-Demir G.; Allen A.B.; Antel J.P.; Antiguedad A.R.; Apperson M.; Applebee A.M.; Ayuso G.I.; Baba M.; Bajenaru O.; Balasa R.; Balci B.P.; Barnett M.; Bass A.; Becker V.U.; Bejinariu M.; Bergh F.T.; Bergmann A.; Bernitsas E.; Berthele A.; Bhan V.; Bischof F.; Bjork R.J.; Blevins G.; Boehringer M.; Boerner T.; Bonek R.; Bowen J.D.; Bowling A.; Boyko A.N.; Boz C.; Bracknies V.; Braune S.; Brescia Morra V.; Brochet B.; Brola W.; Brownstone P.K.; Brozman M.; Brunet D.; Buraga I.; Burnett M.; Buttmann M.; Butzkueven H.; Cahill J.; Calkwood J.C.; Camu W.; Cascione M.; Castelnovo G.; Centonze D.; Cerqueira J.; Chan A.; Cimprichova A.; Cohan S.; Comi G.; Conway J.; Cooper J.A.; Corboy J.; Correale J.; Costell B.; Cottrell D.A.; Coyle P.K.; Craner M.; Cui L.; Cunha L.; Czlonkowska A.; da Silva A.M.; de Sa J.; de Seze J.; Debouverie M.; Debruyne J.; Decoo D.; Defer G.; Derfuss T.; Deri N.H.; Dihenia B.; Dioszeghy P.; Donath V.; Dubois B.; Duddy M.; Duquette P.; Edan G.; Efendi H.; Elias S.; Emrich P.J.; Estruch B.C.; Evdoshenko E.P.; Faiss J.; Fedyanin A.S.; Feneberg W.; Fermont J.; Fernandez O.F.; Ferrer F.C.; Fink K.; Ford H.; Ford C.; Francia A.; Freedman M.; Frishberg B.; Galgani S.; Garmany G.P.; Gehring K.; Gitt J.; Gobbi C.; Goldstick L.P.; Gonzalez R.A.; Grandmaison F.; Grigoriadis N.; Grigorova O.; Grimaldi L.M.E.; Gross J.; Gross-Paju K.; Gudesblatt M.; Guillaume D.; Haas J.; Hancinova V.; Hancu A.; Hardiman O.; Harmjanz A.; Heidenreich F.R.; Hengstman G.J.D.; Herbert J.; Herring M.; Hodgkinson S.; Hoffmann O.M.; Hofmann W.E.; Honeycutt W.D.; Hua L.H.; Huang D.; Huang Y.; Huang D.; Hupperts R.; Imre P.; Jacobs A.K.; Jakab G.; Jasinska E.; Kaida K.; Kalnina J.; Kaprelyan A.; Karelis G.; Karussis D.; Katz A.; Khabirov F.A.; Khatri B.; Kimura T.; Kister I.; Kizlaitiene R.; Klimova E.; Koehler J.; Komatineni A.; Kornhuber A.; Kovacs K.; Koves A.; Kozubski W.; Krastev G.; Krupp L.B.; Kurca E.; Lassek C.; Laureys G.; Lee L.; Lensch E.; Leutmezer F.; Li H.; Linker R.A.; Linnebank M.; Liskova P.; Llanera C.; Lu J.; Lutterotti A.; Lycke J.; Macdonell R.; Maciejowski M.; Maeurer M.; Magzhanov R.V.; Maida E.-M.; Malciene L.; Mao-Draayer Y.; Marfia G.A.; Markowitz C.; Mastorodimos V.; Matyas K.; Meca-Lallana J.; Merino J.A.G.; Mihetiu I.G.; Milanov I.; Miller A.E.; Millers A.; Mirabella M.; Mizuno M.; Montalban X.; Montoya L.; Mori M.; Mueller S.; Nakahara J.; Nakatsuji Y.; Newsome S.; Nicholas R.; Nielsen A.S.; Nikfekr E.; Nocentini U.; Nohara C.; Nomura K.; Odinak M.M.; Olsson T.; van Oosten B.W.; Oreja-Guevara C.; Oschmann P.; Overell J.; Pachner A.; Panczel G.; Pandolfo M.; Papeix C.; Patrucco L.; Pelletier J.; Piedrabuena R.; Pless M.; Polzer U.; Pozsegovits K.; Rastenyte D.; Rauer S.; Reifschneider G.; Rey R.; Rizvi S.A.; Robertson D.; Rodriguez J.M.; Rog D.; Roshanisefat H.; Rowe V.; Rozsa C.; Rubin S.; Rusek S.; Sacca F.; Saida T.; Salgado A.V.; Sanchez V.E.F.; Sanders K.; Satori M.; Sazonov D.V.; Scarpini E.A.; Schlegel E.; Schluep M.; Schmidt S.; Scholz E.; Schrijver H.M.; Schwab M.; Schwartz R.; Scott J.; Selmaj K.; Shafer S.; Sharrack B.; Shchukin I.A.; Shimizu Y.; Shotekov P.; Siever A.; Sigel K.-O.; Silliman S.; Simo M.; Simu M.; Sinay V.; Siquier A.E.; Siva A.; Skoda O.; Solomon A.; Stangel M.; Stefoski D.; Steingo B.; Stolyarov I.D.; Stourac P.; Strassburger-Krogias K.; Strauss E.; Stuve O.; Tarnev I.; Tavernarakis A.; Tello C.R.; Terzi M.; Ticha V.; Ticmeanu M.; Tiel-Wilck K.; Toomsoo T.; Tubridy N.; Tullman M.J.; Tumani H.; Turcani P.; Turner B.; Uccelli A.; Urtaza F.J.O.; Vachova M.; Valikovics A.; Walter S.; Van Wijmeersch B.; Vanopdenbosch L.; Weber J.R.; Weiss S.; Weissert R.; Vermersch P.; West T.; Wiendl H.; Wiertlewski S.; Wildemann B.; Willekens B.; Visser L.H.; Vorobeychik G.; Xu X.; Yamamura T.; Yang Y.N.; Yelamos S.M.; Yeung M.; Zacharias A.; Zelkowitz M.; Zettl U.; Zhang M.; Zhou H.; Zieman U.; Ziemssen T.Kappos, L.; Bar-Or, A.; Cree, B. A. C.; Fox, R. J.; Giovannoni, G.; Gold, R.; Vermersch, P.; Arnold, D. L.; Arnould, S.; Scherz, T.; Wolf, C.; Wallstrom, E.; Dahlke, F.; Achiron, A.; Achtnichts, L.; Agan, K.; Akman-Demir, G.; Allen, A. B.; Antel, J. P.; Antiguedad, A. R.; Apperson, M.; Applebee, A. M.; Ayuso, G. I.; Baba, M.; Bajenaru, O.; Balasa, R.; Balci, B. P.; Barnett, M.; Bass, A.; Becker, V. U.; Bejinariu, M.; Bergh, F. T.; Bergmann, A.; Bernitsas, E.; Berthele, A.; Bhan, V.; Bischof, F.; Bjork, R. J.; Blevins, G.; Boehringer, M.; Boerner, T.; Bonek, R.; Bowen, J. D.; Bowling, A.; Boyko, A. N.; Boz, C.; Bracknies, V.; Braune, S.; Brescia Morra, V.; Brochet, B.; Brola, W.; Brownstone, P. K.; Brozman, M.; Brunet, D.; Buraga, I.; Burnett, M.; Buttmann, M.; Butzkueven, H.; Cahill, J.; Calkwood, J. C.; Camu, W.; Cascione, M.; Castelnovo, G.; Centonze, D.; Cerqueira, J.; Chan, A.; Cimprichova, A.; Cohan, S.; Comi, G.; Conway, J.; Cooper, J. A.; Corboy, J.; Correale, J.; Costell, B.; Cottrell, D. A.; Coyle, P. K.; Craner, M.; Cui, L.; Cunha, L.; Czlonkowska, A.; da Silva, A. M.; de Sa, J.; de Seze, J.; Debouverie, M.; Debruyne, J.; Decoo, D.; Defer, G.; Derfuss, T.; Deri, N. H.; Dihenia, B.; Dioszeghy, P.; Donath, V.; Dubois, B.; Duddy, M.; Duquette, P.; Edan, G.; Efendi, H.; Elias, S.; Emrich, P. J.; Estruch, B. C.; Evdoshenko, E. P.; Faiss, J.; Fedyanin, A. S.; Feneberg, W.; Fermont, J.; Fernandez, O. F.; Ferrer, F. C.; Fink, K.; Ford, H.; Ford, C.; Francia, A.; Freedman, M.; Frishberg, B.; Galgani, S.; Garmany, G. P.; Gehring, K.; Gitt, J.; Gobbi, C.; Goldstick, L. P.; Gonzalez, R. A.; Grandmaison, F.; Grigoriadis, N.; Grigorova, O.; Grimaldi, L. M. E.; Gross, J.; Gross-Paju, K.; Gudesblatt, M.; Guillaume, D.; Haas, J.; Hancinova, V.; Hancu, A.; Hardiman, O.; Harmjanz, A.; Heidenreich, F. R.; Hengstman, G. J. D.; Herbert, J.; Herring, M.; Hodgkinson, S.; Hoffmann, O. M.; Hofmann, W. E.; Honeycutt, W. D.; Hua, L. H.; Huang, D.; Huang, Y.; Huang, D.; Hupperts, R.; Imre, P.; Jacobs, A. K.; Jakab, G.; Jasinska, E.; Kaida, K.; Kalnina, J.; Kaprelyan, A.; Karelis, G.; Karussis, D.; Katz, A.; Khabirov, F. A.; Khatri, B.; Kimura, T.; Kister, I.; Kizlaitiene, R.; Klimova, E.; Koehler, J.; Komatineni, A.; Kornhuber, A.; Kovacs, K.; Koves, A.; Kozubski, W.; Krastev, G.; Krupp, L. B.; Kurca, E.; Lassek, C.; Laureys, G.; Lee, L.; Lensch, E.; Leutmezer, F.; Li, H.; Linker, R. A.; Linnebank, M.; Liskova, P.; Llanera, C.; Lu, J.; Lutterotti, A.; Lycke, J.; Macdonell, R.; Maciejowski, M.; Maeurer, M.; Magzhanov, R. V.; Maida, E. -M.; Malciene, L.; Mao-Draayer, Y.; Marfia, G. A.; Markowitz, C.; Mastorodimos, V.; Matyas, K.; Meca-Lallana, J.; Merino, J. A. G.; Mihetiu, I. G.; Milanov, I.; Miller, A. E.; Millers, A.; Mirabella, M.; Mizuno, M.; Montalban, X.; Montoya, L.; Mori, M.; Mueller, S.; Nakahara, J.; Nakatsuji, Y.; Newsome, S.; Nicholas, R.; Nielsen, A. S.; Nikfekr, E.; Nocentini, U.; Nohara, C.; Nomura, K.; Odinak, M. M.; Olsson, T.; van Oosten, B. W.; Oreja-Guevara, C.; Oschmann, P.; Overell, J.; Pachner, A.; Panczel, G.; Pandolfo, M.; Papeix, C.; Patrucco, L.; Pelletier, J.; Piedrabuena, R.; Pless, M.; Polzer, U.; Pozsegovits, K.; Rastenyte, D.; Rauer, S.; Reifschneider, G.; Rey, R.; Rizvi, S. A.; Robertson, D.; Rodriguez, J. M.; Rog, D.; Roshanisefat, H.; Rowe, V.; Rozsa, C.; Rubin, S.; Rusek, S.; Sacca, F.; Saida, T.; Salgado, A. V.; Sanchez, V. E. F.; Sanders, K.; Satori, M.; Sazonov, D. V.; Scarpini, E. A.; Schlegel, E.; Schluep, M.; Schmidt, S.; Scholz, E.; Schrijver, H. M.; Schwab, M.; Schwartz, R.; Scott, J.; Selmaj, K.; Shafer, S.; Sharrack, B.; Shchukin, I. A.; Shimizu, Y.; Shotekov, P.; Siever, A.; Sigel, K. -O.; Silliman, S.; Simo, M.; Simu, M.; Sinay, V.; Siquier, A. E.; Siva, A.; Skoda, O.; Solomon, A.; Stangel, M.; Stefoski, D.; Steingo, B.; Stolyarov, I. D.; Stourac, P.; Strassburger-Krogias, K.; Strauss, E.; Stuve, O.; Tarnev, I.; Tavernarakis, A.; Tello, C. R.; Terzi, M.; Ticha, V.; Ticmeanu, M.; Tiel-Wilck, K.; Toomsoo, T.; Tubridy, N.; Tullman, M. J.; Tumani, H.; Turcani, P.; Turner, B.; Uccelli, A.; Urtaza, F. J. O.; Vachova, M.; Valikovics, A.; Walter, S.; Van Wijmeersch, B.; Vanopdenbosch, L.; Weber, J. R.; Weiss, S.; Weissert, R.; Vermersch, P.; West, T.; Wiendl, H.; Wiertlewski, S.; Wildemann, B.; Willekens, B.; Visser, L. H.; Vorobeychik, G.; Xu, X.; Yamamura, T.; Yang, Y. N.; Yelamos, S. M.; Yeung, M.; Zacharias, A.; Zelkowitz, M.; Zettl, U.; Zhang, M.; Zhou, H.; Zieman, U.; Ziemssen, T