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101. MS FIRST-utilising a drug safety module for use in MS clinical practice to evaluate lymphocyte reduction in fingolimod treatment over time, demographic predictors of lymphopenia and association with reported safety events.

Author: Slee M., Butler E., Burke T., Rath L., Lechner-Scott J., Taylor B., Vucic S., Barnett M., Hodgkinson S., Spelman T., Butzkueven H., Tan I.L., Hardy T., Shaw C., Shuey N., Kermode A., Skibina O., Haartsen J., Agland S., Baker J., Slee M., Butler E., Burke T., Rath L., Lechner-Scott J., Taylor B., Vucic S., Barnett M., Hodgkinson S., Spelman T., Butzkueven H., Tan I.L., Hardy T., Shaw C., Shuey N., Kermode A., Skibina O., Haartsen J., Agland S., and Baker J.
Abstract: Introduction: MS FIRST, a sub-study of the MSBase registry, is an Australian multi-centre study to implement a user-friendly safety module to track incidence and characteristics of on treatment safety outcomes, including evaluation over time of lymphocyte counts on fingolimod treated patients. Objective(s): To track the incidence of lymphopenic events and safety outcomes in MS patients on fingolimod, we investigated demographic data, baseline disability, pre-baseline relapse activity and pre-fingolimod disease modifying drug exposure as correlates of fingolimod related lymphopenia. Method(s): Data was extracted from the MSBase Registry database in April 2015. There were 2703 patients enrolled in the study, 1920 contributed at least one post-baseline visit. Predictors of time to first lymphopenic event were investigated using a Cox proportional hazard regression, clustered for the patient. Result(s): 1042 patients contributed 1096 fingolimod commencements. 604, 119 and 28 lymphopenic events were observed with counts < 0.5, <= 49.3) and 8.5 (4.4, 15.2) respectively. Median (IQR) baseline EDSS was 2 (1.5, 4). Female sex was associated with an increased rate of both a < 0.5 lymphopenic event (adjusted HR: 1.44, 95% CI 1.14, 182) and <=0.2 lymphopenic event (aHR: 1.78, 95% CI 1.02, 3.10). Conversely a higher baseline lymphocyte count was associated with a 34% reduction in the rate of a < 0.5 lymphopenic event (aHR 0.66, 95% CI 0.59, 0.73) and a 41% reduction of a <=0.2 lymphopenic event (aHR 0.59, 95% CI 0.41, 0.83). Relapse activity in the 12 months prior to commencing fingolimod was correlated with < 0.2 lymphopenic events, with every relapse associated with a 55% reduction in event rate (aHR 0.45, 95% CI 0.22, 0.92). 28 prospectively-observed infective SAEs occurred, 26 Zoster events, 10 malignancies (excluding non melanoma skin cancer, NMSC) and 14 NMSC were recorded on fingolimod. Conclusion(s): The establishment of a prospective multi-drug safety module has been su
Published: 2015

102. A new era in the treatment of multiple sclerosis

Author: Broadley, S.A., Barnett, M.H., Boggild, M., Brew, B.J., Butzkueven, H., Heard, R., Hodgkinson, S., Kermode, A.G., Lechner-Scott, J., Macdonell, R.A.L., Marriott, M., Mason, D.F., Parratt, J., Reddel, S.W., Shaw, C.P., Slee, M., Spies, J.M., Taylor, B.V., Carroll, W.M., Kilpatrick, T.J., King, J., McCombe, P.A., Pollard, J.D., Willoughby, E., Broadley, S.A., Barnett, M.H., Boggild, M., Brew, B.J., Butzkueven, H., Heard, R., Hodgkinson, S., Kermode, A.G., Lechner-Scott, J., Macdonell, R.A.L., Marriott, M., Mason, D.F., Parratt, J., Reddel, S.W., Shaw, C.P., Slee, M., Spies, J.M., Taylor, B.V., Carroll, W.M., Kilpatrick, T.J., King, J., McCombe, P.A., Pollard, J.D., and Willoughby, E.
Abstract: • Multiple sclerosis (MS) is an autoimmune disease of the central nervous system with a multifactorial aetiology and highly variable natural history. • A growing understanding of the immunopathogenesis of the condition has led to an expanding array of therapies for this previously untreatable disease. • While a cure for MS remains elusive, the potential to reduce inflammatory disease activity by preventing relapses and minimising disease progression is achievable. • The importance of early treatment in minimising long-term disability is increasingly recognised. • Most of the newer, more effective therapies are associated with risks and practical problems that necessitate an active management strategy and continuous vigilance. • While the initiation of these therapies is likely to remain the responsibility of neurologists, other specialist physicians and general practitioners will be involved in the identification and management of adverse effects.
Published: 2015

103. Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

Author: Goris, A., Pauwels, I., Gustavsen, M.W., van Son, B., Hilven, K., Bos, S.D., Celius, E.G., Berg-Hansen, P., Aarseth, J., Myhr, K-M, D'Alfonso, S., Barizzone, N., Leone, M.A., Martinelli Boneschi, F., Sorosina, M., Liberatore, G., Kockum, I., Olsson, T., Hillert, J., Alfredsson, L., Bedri, S.K., Hemmer, B., Buck, D., Berthele, A., Knier, B., Biberacher, V., van Pesch, V., Sindic, C., Bang Oturai, A., Sondergaard, H.B., Sellebjerg, F., Jensen, P.E.H., Comabella, M., Montalban, X., Perez-Boza, J., Malhotra, S., Lechner-Scott, J., Broadley, S., Slee, M., Taylor, B., Kermode, A.G., Gourraud, P-A, Sawcer, S.J., Andreassen, B.K., Dubois, B., Harbo, H.F., Goris, A., Pauwels, I., Gustavsen, M.W., van Son, B., Hilven, K., Bos, S.D., Celius, E.G., Berg-Hansen, P., Aarseth, J., Myhr, K-M, D'Alfonso, S., Barizzone, N., Leone, M.A., Martinelli Boneschi, F., Sorosina, M., Liberatore, G., Kockum, I., Olsson, T., Hillert, J., Alfredsson, L., Bedri, S.K., Hemmer, B., Buck, D., Berthele, A., Knier, B., Biberacher, V., van Pesch, V., Sindic, C., Bang Oturai, A., Sondergaard, H.B., Sellebjerg, F., Jensen, P.E.H., Comabella, M., Montalban, X., Perez-Boza, J., Malhotra, S., Lechner-Scott, J., Broadley, S., Slee, M., Taylor, B., Kermode, A.G., Gourraud, P-A, Sawcer, S.J., Andreassen, B.K., Dubois, B., and Harbo, H.F.
Abstract: Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index—the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10−16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10−7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10−37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10−22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10−6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such as female gender
Published: 2015

104. Multiple sclerosis in Latin America: A different disease course severity? A collaborative study from the MSBase Registry

Author: Rojas, JI, Patrucco, L, Trojano, M, Lugaresi, A, Izquierdo, G, Butzkueven, H, Jokubaitis, V, Duquette, P, Girard, M, Grand’Maison, F, Grammond, P, Oreja-Guevara, C, Hupperts, R, Boz, C, Petersen, T, Bergamaschi, R, Giuliani, G, Lechner-Scott, J, Barnett, M, Rio, ME, Van Pesch, V, Amato, MP, Iuliano, G, Fiol, M, Slee, M, Verheul, F, Fernandez-Bolanos, R, Poehlau, D, Saladino, ML, Braber-Moerland, LD, Deri, N, Oleschko-Arruda, W, Cabrera-Gomez, JA, Paine, M, Vella, N, Kister, I, Skromne, E, Savino, A, Shaw, Cameron, Moore, F, Vucic, S, Petkovska-Boskova, T, Bacile, EAB, Santiago, V, Cristiano, E, Rojas, JI, Patrucco, L, Trojano, M, Lugaresi, A, Izquierdo, G, Butzkueven, H, Jokubaitis, V, Duquette, P, Girard, M, Grand’Maison, F, Grammond, P, Oreja-Guevara, C, Hupperts, R, Boz, C, Petersen, T, Bergamaschi, R, Giuliani, G, Lechner-Scott, J, Barnett, M, Rio, ME, Van Pesch, V, Amato, MP, Iuliano, G, Fiol, M, Slee, M, Verheul, F, Fernandez-Bolanos, R, Poehlau, D, Saladino, ML, Braber-Moerland, LD, Deri, N, Oleschko-Arruda, W, Cabrera-Gomez, JA, Paine, M, Vella, N, Kister, I, Skromne, E, Savino, A, Shaw, Cameron, Moore, F, Vucic, S, Petkovska-Boskova, T, Bacile, EAB, Santiago, V, and Cristiano, E
Abstract: Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions. Methods Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and <30 years at time of EDSS measurement were evaluated. The MS Severity Score (MSSS) was used as a measure of disease progression. Comparisons among regions (North America, Europe, Australia and LA), hemispheres and countries were performed. Results A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47 ± 2.8, 4.53 ± 2.8 in North America, 4.51 ± 2.8 in Europe and 4.49 ± 2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51 ± 1.6 compared to 4.48 ± 1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres ( p = 0.68), regions ( p = 0.96) or countries ( p = 0.50). Conclusions Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries.
Published: 2015

105. Effect of relapse phenotype on the accumulation of disability in relapsing-remitting multiple sclerosis

Author: Stewart, T, Jokubaitis, V, Spelman, T, Havrdova, E, Horakova, D, Trojano, M, Izquierdo, G, Girard, M, Duquette, P, Prat, A, Lugaresi, A, Grammond, P, Grand'Maison, F, Sola, P, Hupperts, R, Petersen, T, Pucci, E, Bergamaschi, R, Boz, C, Oreja-Guevara, C, Lechner-Scott, J, Alroughani, R, Ramo, C, Van Pesch, V, Fernandez-Bolanos, R, Iuliano, G, Rio, ME, Granella, F, Slee, M, Verheul, F, Spitaleri, DLA, Amato, MP, Hodgkinson, S, McCombe, P, Cabrera-Gomez, JA, Barnett, M, Flechter, S, Olascoaga, J, Vucic, S, Sanchez-Menoyo, JL, Cristiano, E, Saladino, ML, Moore, F, Gray, O, Shuey, N, Rozsa, C, Singhal, B, Shaw, C, Butzkueven, H, Kalincik, T, Stewart, T, Jokubaitis, V, Spelman, T, Havrdova, E, Horakova, D, Trojano, M, Izquierdo, G, Girard, M, Duquette, P, Prat, A, Lugaresi, A, Grammond, P, Grand'Maison, F, Sola, P, Hupperts, R, Petersen, T, Pucci, E, Bergamaschi, R, Boz, C, Oreja-Guevara, C, Lechner-Scott, J, Alroughani, R, Ramo, C, Van Pesch, V, Fernandez-Bolanos, R, Iuliano, G, Rio, ME, Granella, F, Slee, M, Verheul, F, Spitaleri, DLA, Amato, MP, Hodgkinson, S, McCombe, P, Cabrera-Gomez, JA, Barnett, M, Flechter, S, Olascoaga, J, Vucic, S, Sanchez-Menoyo, JL, Cristiano, E, Saladino, ML, Moore, F, Gray, O, Shuey, N, Rozsa, C, Singhal, B, Shaw, C, Butzkueven, H, and Kalincik, T
Published: 2015

106. Predictors of disability worsening in clinically isolated syndrome

Author: Jokubaitis, VG, Spelman, T, Kalincik, T, Izquierdo, G, Grand'Maison, F, Duquette, P, Girard, M, Lugaresi, A, Grammond, P, Hupperts, R, Cabrera-Gomez, J, Oreja-Guevara, C, Boz, C, Giuliani, G, Fernandez-Bolanos, R, Iuliano, G, Lechner-Scott, J, Verheul, F, van Pesch, V, Petkovska-Boskova, T, Fiol, M, Moore, F, Cristiano, E, Alroughani, R, Bergamaschi, R, Barnett, M, Slee, M, Vella, N, Herbert, J, Shaw, C, Saladino, ML, Amato, MP, Liew, D, Paolicelli, D, Butzkueven, H, Trojano, M, Jokubaitis, VG, Spelman, T, Kalincik, T, Izquierdo, G, Grand'Maison, F, Duquette, P, Girard, M, Lugaresi, A, Grammond, P, Hupperts, R, Cabrera-Gomez, J, Oreja-Guevara, C, Boz, C, Giuliani, G, Fernandez-Bolanos, R, Iuliano, G, Lechner-Scott, J, Verheul, F, van Pesch, V, Petkovska-Boskova, T, Fiol, M, Moore, F, Cristiano, E, Alroughani, R, Bergamaschi, R, Barnett, M, Slee, M, Vella, N, Herbert, J, Shaw, C, Saladino, ML, Amato, MP, Liew, D, Paolicelli, D, Butzkueven, H, and Trojano, M
Abstract: OBJECTIVE: To assess demographic, clinical, magnetic resonance imaging, and treatment exposure predictors of time to 3 or 12-month confirmed disability worsening in clinically isolated syndrome (CIS) and early multiple sclerosis (MS). METHODS: We utilized the MSBase Incident Study (MSBasis), a prospective cohort study of outcome after CIS. Predictors of time to first 3 and 12-month confirmed expanded disability status scale worsening were analyzed using Cox proportional hazards regression. RESULTS: About 1989 patients were analyzed, the largest seen-from-onset cohort reported to-date. A total of 391 patients had a first 3-month confirmed disability worsening event, of which 307 were sustained for 12 months. Older age at CIS onset (adjusted hazard ratio: aHR 1.17, 95% 1.06, 1.30), pyramidal (aHR 1.45, 95% CI 1.13, 1.89) and ambulation (HR 1.60, 95% CI 1.09, 2.34) system dysfunction, annualized relapse rate (aHR 1.20, 95% CI 1.18, 1.22), and lower proportion of observation time on treatment were associated with 3-month confirmed worsening. Predictors of time to 12-month sustained worsening included pyramidal system dysfunction (Hazard ratio: aHR 1.38, 95% CI 1.05, 1.83), and older age at CIS onset (aHR 1.17, 95% CI 1.04, 1.31). Greater proportion of follow-up time exposed to treatment was associated with greater reductions in the rate of worsening. INTERPRETATION: This study provides class IV evidence for a strong protective effect of disease-modifying treatment to reduce disability worsening events in patients with CIS and early MS, and confirms age and pyramidal dysfunction at onset as risk factors.
Published: 2015

107. Defining reliable disability outcomes in multiple sclerosis

Author: Kalincik, T, Cutter, G, Spelman, T, Jokubaitis, V, Havrdova, E, Horakova, D, Trojano, M, Izquierdo, G, Girard, M, Duquette, P, Prat, A, Lugaresi, A, Grand'Maison, F, Grammond, P, Hupperts, R, Oreja-Guevara, C, Boz, C, Pucci, E, Bergamaschi, R, Lechner-Scott, J, Alroughani, R, Van Pesch, V, Iuliano, G, Fernandez-Bolanos, R, Ramo, C, Terzi, M, Slee, M, Spitaleri, D, Verheul, F, Cristiano, E, Luis Sanchez-Menoyo, J, Fiol, M, Gray, O, Antonio Cabrera-Gomez, J, Barnett, M, Butzkueven, H, Kalincik, T, Cutter, G, Spelman, T, Jokubaitis, V, Havrdova, E, Horakova, D, Trojano, M, Izquierdo, G, Girard, M, Duquette, P, Prat, A, Lugaresi, A, Grand'Maison, F, Grammond, P, Hupperts, R, Oreja-Guevara, C, Boz, C, Pucci, E, Bergamaschi, R, Lechner-Scott, J, Alroughani, R, Van Pesch, V, Iuliano, G, Fernandez-Bolanos, R, Ramo, C, Terzi, M, Slee, M, Spitaleri, D, Verheul, F, Cristiano, E, Luis Sanchez-Menoyo, J, Fiol, M, Gray, O, Antonio Cabrera-Gomez, J, Barnett, M, and Butzkueven, H
Abstract: Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally, we evaluated the clinical and demographic determinants characterising progression events and, for those that regressed back to baseline, determinants of their subsequent regression. The study population consisted of 16 636 patients with the minimum of three recorded disability scores, totalling 112 584 patient-years. The progression rates varied between 0.41 and 1.14 events per 10 years, with the length of required confirmation interval as the most important determinant of the observed variance. The concordance among all tested progression criteria was only 17.3%. Regression of disability occurred in 11-34% of the progression events over the five subsequent years. The most important determinant of progression stability was the length of the confirmation period. For the most accurate set of the progression criteria, the proportions of 3-, 6-, 12- or 24-month confirmed events persistent over 5 years reached 70%, 74%, 80% and 89%, respectively. Regression post progression was more common in
Published: 2015

108. Male Sex Is Independently Associated with Faster Disability Accumulation in Relapse-Onset MS but Not in Primary Progressive MS

Author: Aktas, O, Ribbons, KA, McElduff, P, Boz, C, Trojano, M, Izquierdo, G, Duquette, P, Girard, M, Grand'Maison, F, Hupperts, R, Grammond, P, Oreja-Guevara, C, Petersen, T, Bergamaschi, R, Giuliani, G, Barnett, M, van Pesch, V, Amato, M-P, Iuliano, G, Fiol, M, Slee, M, Verheul, F, Cristiano, E, Fernandez-Bolanos, R, Saladino, M-L, Rio, ME, Cabrera-Gomez, J, Butzkueven, H, van Munster, E, Den Braber-Moerland, L, La Spitaleri, D, Lugaresi, A, Shaygannejad, V, Gray, O, Deri, N, Alroughani, R, Lechner-Scott, J, Aktas, O, Ribbons, KA, McElduff, P, Boz, C, Trojano, M, Izquierdo, G, Duquette, P, Girard, M, Grand'Maison, F, Hupperts, R, Grammond, P, Oreja-Guevara, C, Petersen, T, Bergamaschi, R, Giuliani, G, Barnett, M, van Pesch, V, Amato, M-P, Iuliano, G, Fiol, M, Slee, M, Verheul, F, Cristiano, E, Fernandez-Bolanos, R, Saladino, M-L, Rio, ME, Cabrera-Gomez, J, Butzkueven, H, van Munster, E, Den Braber-Moerland, L, La Spitaleri, D, Lugaresi, A, Shaygannejad, V, Gray, O, Deri, N, Alroughani, R, and Lechner-Scott, J
Abstract: BACKGROUND: Multiple Sclerosis is more common in women than men and females have more relapses than men. In a large international cohort we have evaluated the effect of gender on disability accumulation and disease progression to determine if male MS patients have a worse clinical outcome than females. METHODS: Using the MSBase Registry, data from 15,826 MS patients from 25 countries was analysed. Changes in the severity of MS (EDSS) were compared between sexes using a repeated measures analysis in generalised linear mixed models. Kaplan-Meier analysis was used to test for sex difference in the time to reach EDSS milestones 3 and 6 and the secondary progressive MS. RESULTS: In relapse onset MS patients (n = 14,453), males progressed significantly faster in their EDSS than females (0.133 vs 0.112 per year, P<0.001,). Females had a reduced risk of secondary progressive MS (HR (95% CI) = 0.77 (0.67 to 0.90) P = 0.001). In primary progressive MS (n = 1,373), there was a significant increase in EDSS over time in males and females (P<0.001) but there was no significant sex effect on the annualized rate of EDSS change. CONCLUSION: Among registrants of MSBase, male relapse-onset patients accumulate disability faster than female patients. In contrast, the rate of disability accumulation between male and female patients with primary progressive MS is similar.
Published: 2015

109. Growth patterns of Slash and Caribbean Pine and their hybrids in Queensland

Author: Slee, M. U.
Published: 1972
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110. Crossability values within the slash-caribbeanPinus species complex

Author: Slee, M. U.
Published: 1970
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111. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 2 New and emerging therapies and their efficacy

Author: Broadley, S.A., Barnett, M.H., Boggild, M., Brew, B.J., Butzkueven, H., Heard, R., Hodgkinson, S., Kermode, A.G., Lechner-Scott, J., Macdonell, R.A.L., Marriott, M., Mason, D.F., Parratt, J., Reddel, S.W., Shaw, C.P., Slee, M., Spies, J., Taylor, B.V., Carroll, W.M., Kilpatrick, T.J., King, J., McCombe, P.A., Pollard, J.D., Willoughby, E., Broadley, S.A., Barnett, M.H., Boggild, M., Brew, B.J., Butzkueven, H., Heard, R., Hodgkinson, S., Kermode, A.G., Lechner-Scott, J., Macdonell, R.A.L., Marriott, M., Mason, D.F., Parratt, J., Reddel, S.W., Shaw, C.P., Slee, M., Spies, J., Taylor, B.V., Carroll, W.M., Kilpatrick, T.J., King, J., McCombe, P.A., Pollard, J.D., and Willoughby, E.
Abstract: In Part 2 of this three part review of multiple sclerosis (MS) treatment with a particular focus on the Australian and New Zealand perspective, we review the newer therapies that have recently become available and emerging therapies that have now completed phase III clinical trial programs. We go on to compare the relative efficacies of these newer and emerging therapies alongside the existing therapies. The effectiveness of β-interferon in the treatment of different stages and the different disease courses of MS is critically reviewed with the conclusion that the absolute level of response in term of annualised relapse rates (where relapses occur) and MRI activity are similar, but are disappointing in terms of sustained disability progression for progressive forms of the disease. Finally we review the controversial area of combination therapy for MS. Whilst it remains the case that we have no cure or means of preventing MS, we do have a range of effective therapies that when used appropriately and early in the disease course can have a significant impact on short term and longer term outcomes.
Published: 2014

112. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 3 Treatment practicalities and recommendations

Author: Broadley, S.A., Barnett, M.H., Boggild, M., Brew, B.J., Butzkueven, H., Heard, R., Hodgkinson, S., Kermode, A.G., Lechner-Scott, J., Macdonell, R.A.L., Marriott, M., Mason, D.F., Parratt, J., Reddel, S.W., Shaw, C.P., Slee, M., Spies, J., Taylor, B.V., Carroll, W.M., Kilpatrick, T.J., King, J., McCombe, P.A., Pollard, J.D., Willoughby, E., Broadley, S.A., Barnett, M.H., Boggild, M., Brew, B.J., Butzkueven, H., Heard, R., Hodgkinson, S., Kermode, A.G., Lechner-Scott, J., Macdonell, R.A.L., Marriott, M., Mason, D.F., Parratt, J., Reddel, S.W., Shaw, C.P., Slee, M., Spies, J., Taylor, B.V., Carroll, W.M., Kilpatrick, T.J., King, J., McCombe, P.A., Pollard, J.D., and Willoughby, E.
Abstract: In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high.
Published: 2014

113. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 1 Historical and established therapies

Author: Broadley, S.A., Barnett, M.H., Boggild, M., Brew, B.J., Butzkueven, H., Heard, R., Hodgkinson, S., Kermode, A.G., Lechner-Scott, J., Macdonell, R.A.L., Marriott, M., Mason, D.F., Parratt, J., Reddel, S.W., Shaw, C.P., Slee, M., Spies, J., Taylor, B.V., Carroll, W.M., Kilpatrick, T.J., King, J., McCombe, P.A., Pollard, J.D., Willoughby, E., Broadley, S.A., Barnett, M.H., Boggild, M., Brew, B.J., Butzkueven, H., Heard, R., Hodgkinson, S., Kermode, A.G., Lechner-Scott, J., Macdonell, R.A.L., Marriott, M., Mason, D.F., Parratt, J., Reddel, S.W., Shaw, C.P., Slee, M., Spies, J., Taylor, B.V., Carroll, W.M., Kilpatrick, T.J., King, J., McCombe, P.A., Pollard, J.D., and Willoughby, E.
Abstract: Multiple sclerosis (MS) is a potentially life-changing immune mediated disease of the central nervous system. Until recently, treatment has been largely confined to acute treatment of relapses, symptomatic therapies and rehabilitation. Through persistent efforts of dedicated physicians and scientists around the globe for 160 years, a number of therapies that have an impact on the long term outcome of the disease have emerged over the past 20 years. In this three part series we review the practicalities, benefits and potential hazards of each of the currently available and emerging treatment options for MS. We pay particular attention to ways of abrogating the risks of these therapies and provide advice on the most appropriate indications for using individual therapies. In Part 1 we review the history of the development of MS therapies and its connection with the underlying immunobiology of the disease. The established therapies for MS are reviewed in detail and their current availability and indications in Australia and New Zealand are summarised. We examine the evidence to support their use in the treatment of MS.
Published: 2014

114. Risk of relapse phenotype recurrence in multiple sclerosis

Author: Kalincik, T, Buzzard, K, Jokubaitis, V, Trojano, M, Duquette, P, Izquierdo, G, Girard, M, Lugaresi, A, Grammond, P, Grand'Maison, F, Oreja-Guevara, C, Boz, C, Hupperts, R, Petersen, T, Giuliani, G, Iuliano, G, Lechner-Scott, J, Barnett, M, Bergamaschi, R, Van Pesch, V, Amato, MP, Van Munster, E, Fernandez-Bolanos, R, Verheul, F, Fiol, M, Cristiano, E, Slee, M, Rio, ME, Spitaleri, D, Alroughani, R, Gray, O, Saladino, ML, Flechter, S, Herbert, J, Cabrera-Gomez, JA, Vella, N, Paine, M, Shaw, C, Moore, F, Vucic, S, Savino, A, Singhal, B, Petkovska-Boskova, T, Parratt, J, Sirbu, C-A, Rozsa, C, Liew, D, Butzkueven, H, Kalincik, T, Buzzard, K, Jokubaitis, V, Trojano, M, Duquette, P, Izquierdo, G, Girard, M, Lugaresi, A, Grammond, P, Grand'Maison, F, Oreja-Guevara, C, Boz, C, Hupperts, R, Petersen, T, Giuliani, G, Iuliano, G, Lechner-Scott, J, Barnett, M, Bergamaschi, R, Van Pesch, V, Amato, MP, Van Munster, E, Fernandez-Bolanos, R, Verheul, F, Fiol, M, Cristiano, E, Slee, M, Rio, ME, Spitaleri, D, Alroughani, R, Gray, O, Saladino, ML, Flechter, S, Herbert, J, Cabrera-Gomez, JA, Vella, N, Paine, M, Shaw, C, Moore, F, Vucic, S, Savino, A, Singhal, B, Petkovska-Boskova, T, Parratt, J, Sirbu, C-A, Rozsa, C, Liew, D, and Butzkueven, H
Abstract: OBJECTIVES: The aim was to analyse risk of relapse phenotype recurrence in multiple sclerosis and to characterise the effect of demographic and clinical features on this phenotype. METHODS: Information about relapses was collected using MSBase, an international observational registry. Associations between relapse phenotypes and history of similar relapses or patient characteristics were tested with multivariable logistic regression models. Tendency of relapse phenotypes to recur sequentially was assessed with principal component analysis. RESULTS: Among 14,969 eligible patients (89,949 patient-years), 49,279 phenotypically characterised relapses were recorded. Visual and brainstem relapses occurred more frequently in early disease and in younger patients. Sensory relapses were more frequent in early or non-progressive disease. Pyramidal, sphincter and cerebellar relapses were more common in older patients and in progressive disease. Women presented more often with sensory or visual symptoms. Men were more prone to pyramidal, brainstem and cerebellar relapses. Importantly, relapse phenotype was predicted by the phenotypes of previous relapses. (OR = 1.8-5, p = 10(-14)). Sensory, visual and brainstem relapses showed better recovery than other relapse phenotypes. Relapse severity increased and the ability to recover decreased with age or more advanced disease. CONCLUSION: Relapse phenotype was associated with demographic and clinical characteristics, with phenotypic recurrence significantly more common than expected by chance.
Published: 2014

115. Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

Author: Derfuss, T., Kalincik, T., Spelman, T., Trojano, M., Duquette, P., Izquierdo, G., Grammond, P., Lugaresi, A., Hupperts, R., Cristiano, E., van Pesch, V., Grand’Maison, F., La Spitaleri, D., Rio, M.E., Flechter, S., Oreja-Guevara, C., Giuliani, G., Savino, A., Amato, M.P., Petersen, T., Fernandez-Bolanos, R., Bergamaschi, R., Iuliano, G., Boz, C., Lechner-Scott, J., Deri, N., Gray, O., Verheul, F., Fiol, M., Barnett, M., van Munster, E., Santiago, V., Moore, F., Slee, M., Saladino, M.L., Alroughani, R., Shaw, C., Kasa, K., Petkovska-Boskova, T., den Braber-Moerland, L., Chapman, J., Skromne, E., Herbert, J., Poehlau, D., Needham, M., Bacile, E.A.B., Arruda, W.O., Paine, M., Singhal, B., Vucic, S., Cabrera-Gomez, J.A., Butzkueven, H., Derfuss, T., Kalincik, T., Spelman, T., Trojano, M., Duquette, P., Izquierdo, G., Grammond, P., Lugaresi, A., Hupperts, R., Cristiano, E., van Pesch, V., Grand’Maison, F., La Spitaleri, D., Rio, M.E., Flechter, S., Oreja-Guevara, C., Giuliani, G., Savino, A., Amato, M.P., Petersen, T., Fernandez-Bolanos, R., Bergamaschi, R., Iuliano, G., Boz, C., Lechner-Scott, J., Deri, N., Gray, O., Verheul, F., Fiol, M., Barnett, M., van Munster, E., Santiago, V., Moore, F., Slee, M., Saladino, M.L., Alroughani, R., Shaw, C., Kasa, K., Petkovska-Boskova, T., den Braber-Moerland, L., Chapman, J., Skromne, E., Herbert, J., Poehlau, D., Needham, M., Bacile, E.A.B., Arruda, W.O., Paine, M., Singhal, B., Vucic, S., Cabrera-Gomez, J.A., and Butzkueven, H.
Abstract: OBJECTIVES: To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. METHODS: Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. RESULTS: Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. CONCLUSIONS: Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of t
Published: 2013

116. Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes

Author: Cortes, A., Field, J., Glazov, E.A., Hadler, J., Stankovich, J., Brown, M.A., Baxter, A., Kermode, A.G., Taylor, B., Booth, D.R., Mason, D., Stewart, G.J., Butzkueven, H., Charlesworth, J., Wiley, J., Lechner-Scott, J., Tajouri, L., Griffiths, L., Slee, M., Moscato, P., Scott, R.J., Broadley, S., Vucic, S., Kilpatrick, T.J., Carroll, W.M., Cortes, A., Field, J., Glazov, E.A., Hadler, J., Stankovich, J., Brown, M.A., Baxter, A., Kermode, A.G., Taylor, B., Booth, D.R., Mason, D., Stewart, G.J., Butzkueven, H., Charlesworth, J., Wiley, J., Lechner-Scott, J., Tajouri, L., Griffiths, L., Slee, M., Moscato, P., Scott, R.J., Broadley, S., Vucic, S., Kilpatrick, T.J., and Carroll, W.M.
Abstract: Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies [long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture] in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10(-11), OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.
Published: 2013

117. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis

Author: Kalincik, T., Vivek, V., Jokubaitis, V., Lechner-Scott, J., Trojano, M., Izquierdo, G., Lugaresi, A., Grand'Maison, F., Hupperts, R., Oreja-Guevara, C., Bergamaschi, R., Iuliano, G., Alroughani, R., van Pesch, V., Amato, M.P., Slee, M., Verheul, F., Fernandez-Bolanos, R., Fiol, M., Spitaleri, D.L., Cristiano, E., Gray, O., Cabrera-Gomez, J.A., Shaygannejad, V., Herbert, J., Vucic, S., Needham, M., Petkovska-Boskova, T., Sirbu, C-A, Duquette, P., Girard, M., Grammond, P., Boz, C., Giuliani, G., Rio, M.E., Barnett, M., Flechter, S., Moore, F., Singhal, B., Bacile, E.A., Saladino, M.L., Shaw, C., Skromne, E., Poehlau, D., Vella, N., Spelman, T., Liew, D., Kilpatrick, T.J., Butzkueven, H., Kalincik, T., Vivek, V., Jokubaitis, V., Lechner-Scott, J., Trojano, M., Izquierdo, G., Lugaresi, A., Grand'Maison, F., Hupperts, R., Oreja-Guevara, C., Bergamaschi, R., Iuliano, G., Alroughani, R., van Pesch, V., Amato, M.P., Slee, M., Verheul, F., Fernandez-Bolanos, R., Fiol, M., Spitaleri, D.L., Cristiano, E., Gray, O., Cabrera-Gomez, J.A., Shaygannejad, V., Herbert, J., Vucic, S., Needham, M., Petkovska-Boskova, T., Sirbu, C-A, Duquette, P., Girard, M., Grammond, P., Boz, C., Giuliani, G., Rio, M.E., Barnett, M., Flechter, S., Moore, F., Singhal, B., Bacile, E.A., Saladino, M.L., Shaw, C., Skromne, E., Poehlau, D., Vella, N., Spelman, T., Liew, D., Kilpatrick, T.J., and Butzkueven, H.
Abstract: The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10(-12)). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.
Published: 2013

118. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author: Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., Harbo, H.F., Kockum, I., Hillert, J., Olsson, T., Ban, M., Oksenberg, J.R., Hintzen, R., Barcellos, L.F., Agliardi, C., Alfredsson, L., Alizadeh, M., Anderson, C., Andrews, R., Søndergaard, H.B., Baker, A., Band, G., Baranzini, S.E., Barizzone, N., Barrett, J., Bellenguez, C., Bergamaschi, L., Bernardinelli, L., Berthele, A., Biberacher, V., Binder, T.M.C., Blackburn, H., Bomfim, I.L., Brambilla, P., Broadley, S., Brochet, B., Brundin, L., Buck, D., Butzkueven, H., Caillier, S.J., Camu, W., Carpentier, W., Cavalla, P., Celius, E.G., Coman, I., Comi, G., Corrado, L., Cosemans, L., Cournu-Rebeix, I., Cree, B.A.C., Cusi, D., Damotte, V., Defer, G., Delgado, S.R., Deloukas, P., di Sapio, A., Dilthey, A.T., Donnelly, P., Dubois, B., Duddy, M., Edkins, S., Elovaara, I., Esposito, F., Evangelou, N., Fiddes, B., Field, J., Franke, A., Freeman, C., Frohlich, I.Y., Galimberti, D., Gieger, C., Gourraud, P-A, Graetz, C., Graham, A., Grummel, V., Guaschino, C., Hadjixenofontos, A., Hakonarson, H., Halfpenny, C., Hall, G., Hall, P., Hamsten, A., Harley, J., Harrower, T., Hawkins, C., Hellenthal, G., Hillier, C., Hobart, J., Hoshi, M., Hunt, S.E., Jagodic, M., Jelčić, I., Jochim, A., Kendall, B., Kermode, A., Kilpatrick, T., Koivisto, K., Konidari, I., Korn, T., Kronsbein, H., Langford, C., Larsson, M., Lathrop, M., Lebrun-Frenay, C., Lechner-Scott, J., Lee, M.H., Leone, M.A., Leppä, V., Liberatore, G., Lie, B.A., Lill, C.M., Linden, M., Link, J., Luessi, F., Lycke, J., Macciardi, F., Männistö, S., Manrique, C.P., Martin, R., Martinelli, V., Mason, D., Mazibrada, G., McCabe, C., Mero, I-L, Mescheriakova, J., Moutsianas, L., Myhr, K-M, Nagels, G., Nicholas, R., Nilsson, P., Piehl, F., Pirinen, M., Price, S.E., Quach, H., Reunanen, M., Robberecht, W., Robertson, N.P., Rodegher, M., Rog, D., Salvetti, M., Schnetz-Boutaud, N.C., Sellebjerg, F., Selter, R.C., Schaefer, C., Shaunak, S., Shen, L., Shields, S., Siffrin, V., Slee, M., Sorensen, P.S., Sorosina, M., Sospedra, M., Spurkland, A., Strange, A., Sundqvist, E., Thijs, V., Thorpe, J., Ticca, A., Tienari, P., van Duijn, C., Visser, E.M., Vucic, S., Westerlind, H., Wiley, J.S., Wilkins, A., Wilson, J.F., Winkelmann, J., Zajicek, J., Zindler, E., Haines, J.L., Pericak-Vance, M.A., Ivinson, A.J., Stewart, G., Hafler, D., Hauser, S.L., Compston, A., McVean, G., De Jager, P., Sawcer, S.J., McCauley, J.L., Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., Harbo, H.F., Kockum, I., Hillert, J., Olsson, T., Ban, M., Oksenberg, J.R., Hintzen, R., Barcellos, L.F., Agliardi, C., Alfredsson, L., Alizadeh, M., Anderson, C., Andrews, R., Søndergaard, H.B., Baker, A., Band, G., Baranzini, S.E., Barizzone, N., Barrett, J., Bellenguez, C., Bergamaschi, L., Bernardinelli, L., Berthele, A., Biberacher, V., Binder, T.M.C., Blackburn, H., Bomfim, I.L., Brambilla, P., Broadley, S., Brochet, B., Brundin, L., Buck, D., Butzkueven, H., Caillier, S.J., Camu, W., Carpentier, W., Cavalla, P., Celius, E.G., Coman, I., Comi, G., Corrado, L., Cosemans, L., Cournu-Rebeix, I., Cree, B.A.C., Cusi, D., Damotte, V., Defer, G., Delgado, S.R., Deloukas, P., di Sapio, A., Dilthey, A.T., Donnelly, P., Dubois, B., Duddy, M., Edkins, S., Elovaara, I., Esposito, F., Evangelou, N., Fiddes, B., Field, J., Franke, A., Freeman, C., Frohlich, I.Y., Galimberti, D., Gieger, C., Gourraud, P-A, Graetz, C., Graham, A., Grummel, V., Guaschino, C., Hadjixenofontos, A., Hakonarson, H., Halfpenny, C., Hall, G., Hall, P., Hamsten, A., Harley, J., Harrower, T., Hawkins, C., Hellenthal, G., Hillier, C., Hobart, J., Hoshi, M., Hunt, S.E., Jagodic, M., Jelčić, I., Jochim, A., Kendall, B., Kermode, A., Kilpatrick, T., Koivisto, K., Konidari, I., Korn, T., Kronsbein, H., Langford, C., Larsson, M., Lathrop, M., Lebrun-Frenay, C., Lechner-Scott, J., Lee, M.H., Leone, M.A., Leppä, V., Liberatore, G., Lie, B.A., Lill, C.M., Linden, M., Link, J., Luessi, F., Lycke, J., Macciardi, F., Männistö, S., Manrique, C.P., Martin, R., Martinelli, V., Mason, D., Mazibrada, G., McCabe, C., Mero, I-L, Mescheriakova, J., Moutsianas, L., Myhr, K-M, Nagels, G., Nicholas, R., Nilsson, P., Piehl, F., Pirinen, M., Price, S.E., Quach, H., Reunanen, M., Robberecht, W., Robertson, N.P., Rodegher, M., Rog, D., Salvetti, M., Schnetz-Boutaud, N.C., Sellebjerg, F., Selter, R.C., Schaefer, C., Shaunak, S., Shen, L., Shields, S., Siffrin, V., Slee, M., Sorensen, P.S., Sorosina, M., Sospedra, M., Spurkland, A., Strange, A., Sundqvist, E., Thijs, V., Thorpe, J., Ticca, A., Tienari, P., van Duijn, C., Visser, E.M., Vucic, S., Westerlind, H., Wiley, J.S., Wilkins, A., Wilson, J.F., Winkelmann, J., Zajicek, J., Zindler, E., Haines, J.L., Pericak-Vance, M.A., Ivinson, A.J., Stewart, G., Hafler, D., Hauser, S.L., Compston, A., McVean, G., De Jager, P., Sawcer, S.J., and McCauley, J.L.
Abstract: Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
Published: 2013

119. Relapse incidence in women and men throughout the course of multiple sclerosis: An MSBase cohort study

Author: Kalincik, T., Vivek, V., Jokubaitis, V.G., Lechner-Scott, J., Trojano, M., Izquierdo, G., Lugaresi, A., Grand'Maison, F., Hupperts, R., Oreja-Guevara, C., Bergamaschi, R., Iuliano, G., Alroughani, R., van Pesch, V., Amato, M.P., Slee, M., Verheul, F., Fernandez-Bolanos, R., Fiol, M., Spitaleri, D., Cristiano, E., Gray, O., Cabrera-Gómez, J.A., Shaygannejad, V., Herbert, J., Vucic, S., Needham, M., Petkovska-Boskova, T., Adella Sirbu, C., Duquette, P., Girard, M., Grammond, P., Boz, C., Giuliani, G., Rio, M., Barnett, M.H., Flechter, S., Moore, F., Singhal, B., Bacie Bacile, E., Saladino, M., Shaw, C., Skromne, E., Vella, N., Spelman, T., Liew, D., Kilpatrick, T., Butzkueven, H., Kalincik, T., Vivek, V., Jokubaitis, V.G., Lechner-Scott, J., Trojano, M., Izquierdo, G., Lugaresi, A., Grand'Maison, F., Hupperts, R., Oreja-Guevara, C., Bergamaschi, R., Iuliano, G., Alroughani, R., van Pesch, V., Amato, M.P., Slee, M., Verheul, F., Fernandez-Bolanos, R., Fiol, M., Spitaleri, D., Cristiano, E., Gray, O., Cabrera-Gómez, J.A., Shaygannejad, V., Herbert, J., Vucic, S., Needham, M., Petkovska-Boskova, T., Adella Sirbu, C., Duquette, P., Girard, M., Grammond, P., Boz, C., Giuliani, G., Rio, M., Barnett, M.H., Flechter, S., Moore, F., Singhal, B., Bacie Bacile, E., Saladino, M., Shaw, C., Skromne, E., Vella, N., Spelman, T., Liew, D., Kilpatrick, T., and Butzkueven, H.
Abstract: Introduction: Only one large retrospective cohort study and several smaller analyses examined predictors of relapse incidence in MS. Sex, age and MS duration were suggested as determinants of relapse activity. While in relapsing-remitting MS women are overrepresented in the ratio of 3:1 to men, in primary progressive disease both sexes are represented equally. A lower probability of relapse in men could be the reason for this change, with primary progressive (PP) MS representing the “extreme” of low relapse activity. Aims: To evaluate effect of sex on the incidence of MS relapses. To assess the hypothesis that the female-to-male ratio increases gradually with relapse activity and that PPMS represents a non-relapsing extreme along this continuum. To directly compare effects of age and MS duration on relapse incidence. Methods: Annualised relapse rates were calculated using the MSBase registry. Patients with incomplete data or less than one year of follow-up were excluded. Patients with PPMS were only included in the sex ratio analysis. Relapse incidences over 40 years of MS duration or up to 70 years of age were compared between females and males using Andersen-Gill and Poisson models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and PPMS. All models were adjusted for therapy and pregnancy. Results: Among 11,570 eligible patients with relapse-onset MS (82,552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared to males. Within the initial five years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 to >=4 relapses per year, respectively. The magnitude of this sex effect increased at longer MS duration and older age. However, the female-to-male ratio in patients with relapse-onset MS and zero relapses in any given year was double that of the patients with PPMS. Patient age was a more important
Published: 2013

120. Symptomatology of multiple sclerosis relapses varies in relation to demographic and clinical factors

Author: Kalincik, T., Buzzard, K., Trojano, M., Duquette, P., Girard, M., Izquierdo, G., Grammond, P., Lugaresi, A., Petersen, T., Hupperts, R., Bergamaschi, R., Boz, C., Giuliani, G., Barnett, M.H., Lechner-Scott, J., Grand'Maison, F., Oreja-Guevara, C., Iuliano, G., Amato, M.P., Verheul, F., Cristiano, E., Fernandez-Bolanos, R., van Pesch, V., Fiol, M., Rio, M., Slee, M., Flechter, S., Gray, O., Saladino, M., Spitaleri, D., Cabrera-Gómez, J.A., Paine, M., Shaw, C., Alroughani, R., Vella, N., Rózsa, C., Vucic, S., Moore, F., Singhal, B., Deri, N., Needham, M., Santiago, V., Herbert, J., Savino, A., Adella Sirbu, C., Petkovska-Boskova, T., Bacile Bacile, E., Jokubaitis, V.G., Liew, D., Butzkueven, H., Kalincik, T., Buzzard, K., Trojano, M., Duquette, P., Girard, M., Izquierdo, G., Grammond, P., Lugaresi, A., Petersen, T., Hupperts, R., Bergamaschi, R., Boz, C., Giuliani, G., Barnett, M.H., Lechner-Scott, J., Grand'Maison, F., Oreja-Guevara, C., Iuliano, G., Amato, M.P., Verheul, F., Cristiano, E., Fernandez-Bolanos, R., van Pesch, V., Fiol, M., Rio, M., Slee, M., Flechter, S., Gray, O., Saladino, M., Spitaleri, D., Cabrera-Gómez, J.A., Paine, M., Shaw, C., Alroughani, R., Vella, N., Rózsa, C., Vucic, S., Moore, F., Singhal, B., Deri, N., Needham, M., Santiago, V., Herbert, J., Savino, A., Adella Sirbu, C., Petkovska-Boskova, T., Bacile Bacile, E., Jokubaitis, V.G., Liew, D., and Butzkueven, H.
Abstract: Introduction: Our knowledge of incidence and outcomes of MS relapses with specific symptomatology is limited. For example, optic neuritis is more common in early MS and the ability to recover deteriorates with longer disease duration. However, a comprehensive evaluation of multiple sclerosis relapse phenotypes, comprising clinical presentations, severity, impact and recovery, and capturing full spectrum of MS courses, duration and patient demography, has not yet been done. Aim: To identify patterns of clinical MS relapses, their impact on specific neuroanatomical locations and their associations with demographic and clinical parameters. Methods: Information about relapse symptomatology was collected prospectively in 17,555 eligible patients and 104,333 patient-years recorded in MSBase, an international observational MS registry. In a proportion of the relapses, information about relapse severity, impact on activities of daily living and recovery was available. Associations between relapse phenotype and patient characteristics were tested with a series of multivariable logistic regression models. Principal component analysis was conducted to assess the tendency of the specific relapse locations to be involved sequentially in individual patients. Results: Of 63,343 relapses, the majority affected pyramidal and sensory functions. Visual and brainstem relapses occurred more frequently in early disease and in younger patients. Sensory relapses were recorded mostly in earlier disease and less commonly in relapsing-progressive disease. Pyramidal, sphincter and cerebellar relapses were more common in older patients and in progressive disease. Women more commonly presented with sensory or visual symptoms, while men were more prone to pyramidal, brainstem and cerebellar relapses. Relapses were likely to recur within the previously affected locations (odd ratios 1.8 – 5, p = 10^-13), with pyramidal, sphincter and sensory relapses often converging within the same individuals (e
Published: 2013

121. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author: Beecham, AH, Patsopoulos, NA, Xifara, DK, Davis, MF, Kemppinen, A, Cotsapas, C, Shah, TS, Spencer, C, Booth, D, Goris, A, Oturai, A, Saarela, J, Fontaine, B, Hemmer, B, Martin, C, Zipp, F, D'Alfonso, S, Martinelli-Boneschi, F, Taylor, B, Harbo, HF, Kockum, I, Hillert, J, Olsson, T, Ban, M, Oksenberg, JR, Hintzen, R, Barcellos, LF, Agliardi, C, Alfredsson, L, Alizadeh, M, Anderson, C, Andrews, R, Sondergaard, HB, Baker, A, Band, G, Baranzini, SE, Barizzone, N, Barrett, J, Bellenguez, C, Bergamaschi, L, Bernardinelli, L, Berthele, A, Biberacher, V, Binder, TMC, Blackburn, H, Bomfim, IL, Brambilla, P, Broadley, S, Brochet, B, Brundin, L, Buck, D, Butzkueven, H, Caillier, SJ, Camu, W, Carpentier, W, Cavalla, P, Celius, EG, Coman, I, Comi, G, Corrado, L, Cosemans, L, Cournu-Rebeix, I, Cree, BAC, Cusi, D, Damotte, V, Defer, G, Delgado, SR, Deloukas, P, di Sapio, A, Dilthey, AT, Donnelly, P, Dubois, B, Duddy, M, Edkins, S, Elovaara, I, Esposito, F, Evangelou, N, Fiddes, B, Field, J, Franke, A, Freeman, C, Frohlich, IY, Galimberti, D, Gieger, C, Gourraud, P-A, Graetz, C, Graham, A, Grummel, V, Guaschino, C, Hadjixenofontos, A, Hakonarson, H, Halfpenny, C, Hall, G, Hall, P, Hamsten, A, Harley, J, Harrower, T, Hawkins, C, Hellenthal, G, Hillier, C, Hobart, J, Hoshi, M, Hunt, SE, Jagodic, M, Jelcic, I, Jochim, A, Kendall, B, Kermode, A, Kilpatrick, T, Koivisto, K, Konidari, I, Korn, T, Kronsbein, H, Langford, C, Larsson, M, Lathrop, M, Lebrun-Frenay, C, Lechner-Scott, J, Lee, MH, Leone, MA, Leppa, V, Liberatore, G, Lie, BA, Lill, CM, Linden, M, Link, J, Luessi, F, Lycke, J, Macciardi, F, Mannisto, S, Manrique, CP, Martin, R, Martinelli, V, Mason, D, Mazibrada, G, McCabe, C, Mero, I-L, Mescheriakova, J, Moutsianas, L, Myhr, K-M, Nagels, G, Nicholas, R, Nilsson, P, Piehl, F, Pirinen, M, Price, SE, Quach, H, Reunanen, M, Robberecht, W, Robertson, NP, Rodegher, M, Rog, D, Salvetti, M, Schnetz-Boutaud, NC, Sellebjerg, F, Selter, RC, Schaefer, C, Shaunak, S, Shen, L, Shields, S, Siffrin, V, Slee, M, Sorensen, PS, Sorosina, M, Sospedra, M, Spurkland, A, Strange, A, Sundqvist, E, Thijs, V, Thorpe, J, Ticca, A, Tienari, P, van Duijn, C, Visser, EM, Vucic, S, Westerlind, H, Wiley, JS, Wilkins, A, Wilson, JF, Winkelmann, J, Zajicek, J, Zindler, E, Haines, JL, Pericak-Vance, MA, Ivinson, AJ, Stewart, G, Hafler, D, Hauser, SL, Compston, A, McVean, G, De Jager, P, Sawcer, SJ, McCauley, JL, Beecham, AH, Patsopoulos, NA, Xifara, DK, Davis, MF, Kemppinen, A, Cotsapas, C, Shah, TS, Spencer, C, Booth, D, Goris, A, Oturai, A, Saarela, J, Fontaine, B, Hemmer, B, Martin, C, Zipp, F, D'Alfonso, S, Martinelli-Boneschi, F, Taylor, B, Harbo, HF, Kockum, I, Hillert, J, Olsson, T, Ban, M, Oksenberg, JR, Hintzen, R, Barcellos, LF, Agliardi, C, Alfredsson, L, Alizadeh, M, Anderson, C, Andrews, R, Sondergaard, HB, Baker, A, Band, G, Baranzini, SE, Barizzone, N, Barrett, J, Bellenguez, C, Bergamaschi, L, Bernardinelli, L, Berthele, A, Biberacher, V, Binder, TMC, Blackburn, H, Bomfim, IL, Brambilla, P, Broadley, S, Brochet, B, Brundin, L, Buck, D, Butzkueven, H, Caillier, SJ, Camu, W, Carpentier, W, Cavalla, P, Celius, EG, Coman, I, Comi, G, Corrado, L, Cosemans, L, Cournu-Rebeix, I, Cree, BAC, Cusi, D, Damotte, V, Defer, G, Delgado, SR, Deloukas, P, di Sapio, A, Dilthey, AT, Donnelly, P, Dubois, B, Duddy, M, Edkins, S, Elovaara, I, Esposito, F, Evangelou, N, Fiddes, B, Field, J, Franke, A, Freeman, C, Frohlich, IY, Galimberti, D, Gieger, C, Gourraud, P-A, Graetz, C, Graham, A, Grummel, V, Guaschino, C, Hadjixenofontos, A, Hakonarson, H, Halfpenny, C, Hall, G, Hall, P, Hamsten, A, Harley, J, Harrower, T, Hawkins, C, Hellenthal, G, Hillier, C, Hobart, J, Hoshi, M, Hunt, SE, Jagodic, M, Jelcic, I, Jochim, A, Kendall, B, Kermode, A, Kilpatrick, T, Koivisto, K, Konidari, I, Korn, T, Kronsbein, H, Langford, C, Larsson, M, Lathrop, M, Lebrun-Frenay, C, Lechner-Scott, J, Lee, MH, Leone, MA, Leppa, V, Liberatore, G, Lie, BA, Lill, CM, Linden, M, Link, J, Luessi, F, Lycke, J, Macciardi, F, Mannisto, S, Manrique, CP, Martin, R, Martinelli, V, Mason, D, Mazibrada, G, McCabe, C, Mero, I-L, Mescheriakova, J, Moutsianas, L, Myhr, K-M, Nagels, G, Nicholas, R, Nilsson, P, Piehl, F, Pirinen, M, Price, SE, Quach, H, Reunanen, M, Robberecht, W, Robertson, NP, Rodegher, M, Rog, D, Salvetti, M, Schnetz-Boutaud, NC, Sellebjerg, F, Selter, RC, Schaefer, C, Shaunak, S, Shen, L, Shields, S, Siffrin, V, Slee, M, Sorensen, PS, Sorosina, M, Sospedra, M, Spurkland, A, Strange, A, Sundqvist, E, Thijs, V, Thorpe, J, Ticca, A, Tienari, P, van Duijn, C, Visser, EM, Vucic, S, Westerlind, H, Wiley, JS, Wilkins, A, Wilson, JF, Winkelmann, J, Zajicek, J, Zindler, E, Haines, JL, Pericak-Vance, MA, Ivinson, AJ, Stewart, G, Hafler, D, Hauser, SL, Compston, A, McVean, G, De Jager, P, Sawcer, SJ, and McCauley, JL
Abstract: Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
Published: 2013

122. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis

Author: Kalincik, T, Vivek, V, Jokubaitis, V, Lechner-Scott, J, Trojano, M, Izquierdo, G, Lugaresi, A, Grand'Maison, F, Hupperts, R, Oreja-Guevara, C, Bergamaschi, R, Iuliano, G, Alroughani, R, Van Pesch, V, Amato, MP, Slee, M, Verheul, F, Fernandez-Bolanos, R, Fiol, M, La Spitaleri, D, Cristiano, E, Gray, O, Antonio Cabrera-Gomez, J, Shaygannejad, V, Herbert, J, Vucic, S, Needham, M, Petkovska-Boskova, T, Sirbu, C-A, Duquette, P, Girard, M, Grammond, P, Boz, C, Giuliani, G, Rio, ME, Barnett, M, Flechter, S, Moore, F, Singhal, B, Alejandra Bacile, E, Laura Saladino, M, Shaw, C, Skromne, E, Poehlau, D, Vella, N, Spelman, T, Liew, D, Kilpatrick, TJ, Butzkueven, H, Kalincik, T, Vivek, V, Jokubaitis, V, Lechner-Scott, J, Trojano, M, Izquierdo, G, Lugaresi, A, Grand'Maison, F, Hupperts, R, Oreja-Guevara, C, Bergamaschi, R, Iuliano, G, Alroughani, R, Van Pesch, V, Amato, MP, Slee, M, Verheul, F, Fernandez-Bolanos, R, Fiol, M, La Spitaleri, D, Cristiano, E, Gray, O, Antonio Cabrera-Gomez, J, Shaygannejad, V, Herbert, J, Vucic, S, Needham, M, Petkovska-Boskova, T, Sirbu, C-A, Duquette, P, Girard, M, Grammond, P, Boz, C, Giuliani, G, Rio, ME, Barnett, M, Flechter, S, Moore, F, Singhal, B, Alejandra Bacile, E, Laura Saladino, M, Shaw, C, Skromne, E, Poehlau, D, Vella, N, Spelman, T, Liew, D, Kilpatrick, TJ, and Butzkueven, H
Abstract: The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10(-12)). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.
Published: 2013

123. AGATA -Advanced GAmma Tracking Array

Author: Akkoyun, S., Algora, A., Alikhani, B., Ameil, F., Angelis, G. de, Arnold, L., Astier, A., Atac, Ayse, Aubert, Y., Aufranc, C., Austin, A., Aydin, S., Azaiez, F., Badoer, S., Balabanski, D. L., Barrientos, D., Baulieu, G., Baumann, R., Bazzacco, D., Beck, F. A., Beck, T., Bednarczyk, P., Bellato, M., Bentley, M. A., Benzoni, G., Berthier, R., Berti, L., Beunard, R., Bianco, G. Lo, Birkenbach, B., Bizzeti, P. G., Bizzeti-Sona, A. M., Blanc, F. Le, Blasco, J. M., Blasi, N., Bloor, D., Boiano, C., Borsato, M., Bortolato, D., Boston, A. J., Boston, H. C., Bourgault, P., Boutachkov, P., Bouty, A., Bracco, A., Brambilla, S., Brawn, I. P., Brondi, A., Broussard, S., Bruyneel, B., Bucurescu, D., Burrows, I., Burger, A., Cabaret, S., Cahan, B., Calore, E., Camera, F., Capsoni, A., Carrio, F., Casati, G., Castoldi, M., Cederwall, B., Cercus, J. -L, Chambert, V., Chambit, M. El, Chapman, R., Charles, L., Chavas, J., Clement, E., Cocconi, P., Coelli, S., Coleman-Smith, P. J., Colombo, A., Colosimo, S., Commeaux, C., Conventi, D., Cooper, R. J., Corsi, A., Cortesi, A., Costa, L., Crespi, F. C. L., Cresswell, J. R., Cullen, D. M., Curien, D., Czermak, A., Delbourg, D., Depalo, R., Descombes, T., Desesquelles, P., Detistov, P., Diarra, C., Didierjean, F., Dimmock, M. R., Doan, Q. T., Domingo-Pardo, C., Doncel, M., Dorangeville, F., Dosme, N., Drouen, Y., DuchÃªne, G., Dulny, B., Eberth, J., Edelbruck, P., Egea, J., Engert, T., Erduran, M. N., Erturk, S., Fanin, C., Fantinel, S., Farnea, E., Faul, T., Filliger, M., Filmer, F., Finck, Ch., France, G. de, Gadea, A., Gast, W., Geraci, A., Gerl, J., Gernhauser, R., Giannatiempo, A., Giaz, A., Gibelin, L., Givechev, A., Goel, N., Gonzalez, V., Gottardo, A., Grave, X., Grebosz, J., Griffiths, R., Grint, A. N., Gros, P., Guevara, L., Gulmini, M., Gorgen, A., Ha, H. T. M., Habermann, T., Harkness, L. J., Harroch, H., Hauschild, K., He, C., Hernandez-Prieto, A., Hervieu, B., Hess, H., Huyuk, T., Ince, E., Isocrate, R., Jaworski, G., Johnson, A., Jolie, J., Jones, P., Jonson, B., Joshi, P., Judson, D. S., Jungclaus, A., Kaci, M., Karkour, N., Karolak, M., Karkour, A., Kebbiri, M., Kempley, R. S., Khaplanov, A., Klupp, S., Kogimtzis, M., Kojouharov, I., Korichi, A., Korten, W., Kroll, Th., Krucken, R., Kurz, N., Ky, B. Y., Labiche, M., Lafay, X., Lavergne, L., Lazarus, I. H., Leboutelier, S., Lefebvre, F., Legay, E., Legeard, L., Lelli, F., Lenzi, S. M., Leoni, S., Lermitage, A., Lersch, D., Leske, J., Letts, S. C., Lhenoret, S., Lieder, R. M., Linget, D., Ljungvall, J., Lopez-Martens, A., Lotode, A., Lunardi, S., Maj, A., Marel, J. van der, Mariette, Y., Marginean, N., Marginean, R., Maron, G., Mather, A. R., Meczynski, W., Mendez, V., Medina, P., Melon, B., Menegazzo, R., Mengoni, D., Merchan, E., Mihailescu, L., Michelagnoli, C., Mierzejewski, J., Milechina, L., Million, B., Mitev, K., Molini, P., Montanari, D., Moon, S., Morbiducci, F., Moro, R., Morrall, P. S., Möller, O., Nannini, A., Napoli, D. R., Nelson, L., Nespolo, M., Ngo, V. L., Nicoletto, M., Nicolini, R., Noa, Y. Le, Nolan, P. J., Norman, M., Nyberg, Johan, Obertelli, A., Olariu, A., Orlandi, R., Oxley, D. C., Ozben, C., Ozille, M., Oziol, C., Pachoud, E., Palacz, M., Palin, J., Pancin, J., Parisel, C., Pariset, P., Pascovici, G., Peghin, R., Pellegri, L., Perego, A., Perrier, S., Petcu, M., Petkov, P., Petrache, C., Pierre, E., Pietralla, N., Pietri, S., Pignanelli, M., Piqueras, I., Podolyak, Z., Pouhalec, P. Le, Pouthas, J., Pugnere, D., Pucknell, V. F. E., Pullia, A., Quintana, B., Raine, R., Rainovski, G., Ramina, L., Rampazzo, G., Rana, G. La, Rebeschini, M., Recchia, F., Redon, N., Reese, M., Reiter, P., Regan, P. H., Riboldi, S., Richer, M., Rigato, M., Rigby, S., Ripamonti, G., Robinson, A. P., Robin, J., Roccaz, J., Ropert, J. -A, Rosse, B., Rossi Alvarez, C., Rosso, D., Rubio, B., Rudolph, D., Saillant, F., Sahin, E., Salomon, F., Salsac, M. -D, Salt, J., Salvato, G., Sampson, J., Sanchis, E., Santos, C., Schaffner, H., Schlarb, M., Scraggs, D. P., Seddon, D., Senyigit, M., Sigward, M. -H, Simpson, G., Simpson, J., Slee, M., Smith, J. F., Sona, P., Sowicki, B., Spolaore, P., Stahl, C., Stanios, T., Stefanova, E., Stezowski, O., Strachan, J., Suliman, G., Söderström, Pär-Anders, Tain, J. L., Tanguy, S., Tashenov, S., Theisen, Ch., Thornhill, J., Tomasi, F., Toniolo, N., Touzery, R., Travers, B., Triossi, A., Tripon, M., Tun-Lanoe, K. M. M., Turcato, M., Unsworth, C., Ur, C. A., Valiente-Dobon, J. J., Vandone, V., Vardaci, E., Venturelli, R., Veronese, F., Veyssiere, Ch., Viscione, E., Wadsworth, R., Walker, P. M., Warr, N., Weber, C., Weisshaar, D., Wells, D., Wieland, O., Wiens, A., Wittwer, G., Wollersheim, H. J., Zocca, F., Zamfir, N. V., Zieblinski, M., Zucchiatti, A., Akkoyun, S., Algora, A., Alikhani, B., Ameil, F., Angelis, G. de, Arnold, L., Astier, A., Atac, Ayse, Aubert, Y., Aufranc, C., Austin, A., Aydin, S., Azaiez, F., Badoer, S., Balabanski, D. L., Barrientos, D., Baulieu, G., Baumann, R., Bazzacco, D., Beck, F. A., Beck, T., Bednarczyk, P., Bellato, M., Bentley, M. A., Benzoni, G., Berthier, R., Berti, L., Beunard, R., Bianco, G. Lo, Birkenbach, B., Bizzeti, P. G., Bizzeti-Sona, A. M., Blanc, F. Le, Blasco, J. M., Blasi, N., Bloor, D., Boiano, C., Borsato, M., Bortolato, D., Boston, A. J., Boston, H. C., Bourgault, P., Boutachkov, P., Bouty, A., Bracco, A., Brambilla, S., Brawn, I. P., Brondi, A., Broussard, S., Bruyneel, B., Bucurescu, D., Burrows, I., Burger, A., Cabaret, S., Cahan, B., Calore, E., Camera, F., Capsoni, A., Carrio, F., Casati, G., Castoldi, M., Cederwall, B., Cercus, J. -L, Chambert, V., Chambit, M. El, Chapman, R., Charles, L., Chavas, J., Clement, E., Cocconi, P., Coelli, S., Coleman-Smith, P. J., Colombo, A., Colosimo, S., Commeaux, C., Conventi, D., Cooper, R. J., Corsi, A., Cortesi, A., Costa, L., Crespi, F. C. L., Cresswell, J. R., Cullen, D. M., Curien, D., Czermak, A., Delbourg, D., Depalo, R., Descombes, T., Desesquelles, P., Detistov, P., Diarra, C., Didierjean, F., Dimmock, M. R., Doan, Q. T., Domingo-Pardo, C., Doncel, M., Dorangeville, F., Dosme, N., Drouen, Y., DuchÃªne, G., Dulny, B., Eberth, J., Edelbruck, P., Egea, J., Engert, T., Erduran, M. N., Erturk, S., Fanin, C., Fantinel, S., Farnea, E., Faul, T., Filliger, M., Filmer, F., Finck, Ch., France, G. de, Gadea, A., Gast, W., Geraci, A., Gerl, J., Gernhauser, R., Giannatiempo, A., Giaz, A., Gibelin, L., Givechev, A., Goel, N., Gonzalez, V., Gottardo, A., Grave, X., Grebosz, J., Griffiths, R., Grint, A. N., Gros, P., Guevara, L., Gulmini, M., Gorgen, A., Ha, H. T. M., Habermann, T., Harkness, L. J., Harroch, H., Hauschild, K., He, C., Hernandez-Prieto, A., Hervieu, B., Hess, H., Huyuk, T., Ince, E., Isocrate, R., Jaworski, G., Johnson, A., Jolie, J., Jones, P., Jonson, B., Joshi, P., Judson, D. S., Jungclaus, A., Kaci, M., Karkour, N., Karolak, M., Karkour, A., Kebbiri, M., Kempley, R. S., Khaplanov, A., Klupp, S., Kogimtzis, M., Kojouharov, I., Korichi, A., Korten, W., Kroll, Th., Krucken, R., Kurz, N., Ky, B. Y., Labiche, M., Lafay, X., Lavergne, L., Lazarus, I. H., Leboutelier, S., Lefebvre, F., Legay, E., Legeard, L., Lelli, F., Lenzi, S. M., Leoni, S., Lermitage, A., Lersch, D., Leske, J., Letts, S. C., Lhenoret, S., Lieder, R. M., Linget, D., Ljungvall, J., Lopez-Martens, A., Lotode, A., Lunardi, S., Maj, A., Marel, J. van der, Mariette, Y., Marginean, N., Marginean, R., Maron, G., Mather, A. R., Meczynski, W., Mendez, V., Medina, P., Melon, B., Menegazzo, R., Mengoni, D., Merchan, E., Mihailescu, L., Michelagnoli, C., Mierzejewski, J., Milechina, L., Million, B., Mitev, K., Molini, P., Montanari, D., Moon, S., Morbiducci, F., Moro, R., Morrall, P. S., Möller, O., Nannini, A., Napoli, D. R., Nelson, L., Nespolo, M., Ngo, V. L., Nicoletto, M., Nicolini, R., Noa, Y. Le, Nolan, P. J., Norman, M., Nyberg, Johan, Obertelli, A., Olariu, A., Orlandi, R., Oxley, D. C., Ozben, C., Ozille, M., Oziol, C., Pachoud, E., Palacz, M., Palin, J., Pancin, J., Parisel, C., Pariset, P., Pascovici, G., Peghin, R., Pellegri, L., Perego, A., Perrier, S., Petcu, M., Petkov, P., Petrache, C., Pierre, E., Pietralla, N., Pietri, S., Pignanelli, M., Piqueras, I., Podolyak, Z., Pouhalec, P. Le, Pouthas, J., Pugnere, D., Pucknell, V. F. E., Pullia, A., Quintana, B., Raine, R., Rainovski, G., Ramina, L., Rampazzo, G., Rana, G. La, Rebeschini, M., Recchia, F., Redon, N., Reese, M., Reiter, P., Regan, P. H., Riboldi, S., Richer, M., Rigato, M., Rigby, S., Ripamonti, G., Robinson, A. P., Robin, J., Roccaz, J., Ropert, J. -A, Rosse, B., Rossi Alvarez, C., Rosso, D., Rubio, B., Rudolph, D., Saillant, F., Sahin, E., Salomon, F., Salsac, M. -D, Salt, J., Salvato, G., Sampson, J., Sanchis, E., Santos, C., Schaffner, H., Schlarb, M., Scraggs, D. P., Seddon, D., Senyigit, M., Sigward, M. -H, Simpson, G., Simpson, J., Slee, M., Smith, J. F., Sona, P., Sowicki, B., Spolaore, P., Stahl, C., Stanios, T., Stefanova, E., Stezowski, O., Strachan, J., Suliman, G., Söderström, Pär-Anders, Tain, J. L., Tanguy, S., Tashenov, S., Theisen, Ch., Thornhill, J., Tomasi, F., Toniolo, N., Touzery, R., Travers, B., Triossi, A., Tripon, M., Tun-Lanoe, K. M. M., Turcato, M., Unsworth, C., Ur, C. A., Valiente-Dobon, J. J., Vandone, V., Vardaci, E., Venturelli, R., Veronese, F., Veyssiere, Ch., Viscione, E., Wadsworth, R., Walker, P. M., Warr, N., Weber, C., Weisshaar, D., Wells, D., Wieland, O., Wiens, A., Wittwer, G., Wollersheim, H. J., Zocca, F., Zamfir, N. V., Zieblinski, M., and Zucchiatti, A.
Abstract: The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate the next generation gamma-ray spectrometer. AGATA is based on the technique of gamma-ray energy tracking in electrically segmented high-purity germanium crystals. This technique requires the accurate determination of the energy, time and position of every interaction as a gamma ray deposits its energy within the detector volume. Reconstruction of the full interaction path results in a detector with very high efficiency and excellent spectral response. The realisation of gamma-ray tracking and AGATA is a result of many technical advances. These include the development of encapsulated highly segmented germanium detectors assembled in a triple cluster detector cryostat, an electronics system with fast digital sampling and a data acquisition system to process the data at a high rate. The full characterisation of the crystals was measured and compared with detector-response simulations. This enabled pulse-shape analysis algorithms, to extract energy, time and position, to be employed. In addition, tracking algorithms for event reconstruction were developed. The first phase of AGATA is now complete and operational in its first physics campaign. In the future AGATA will be moved between laboratories in Europe and operated in a series of campaigns to take advantage of the different beams and facilities available to maximise its science output. The paper reviews all the achievements made in the AGATA project including all the necessary infrastructure to operate and support the spectrometer.
Published: 2012
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124. The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Lechner-Scott, J, Spencer, B, de Malmanche, T, Attia, J, Fitzgerald, M, Trojano, M, Grand'Maison, F, Gomez, J Antonio C, Izquierdo, G, Duquette, P, Girard, M, Grammond, P, Oreja-Guevara, C, Hupperts, R, Bergamaschi, R, Boz, C, Giuliani, G, Van Pesch, Vincent, Iuliano, G, Fiol, M, Cristiano, E, Verheul, F, Saladino, M Laura, Slee, M, Barnett, M, Deri, N, Flechter, S, Vella, N, Shaw, C, Herbert, J, Moore, F, Petkovska-Boskova, T, Jokubaitis, V, Butzkueven, H, MSBase study group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Lechner-Scott, J, Spencer, B, de Malmanche, T, Attia, J, Fitzgerald, M, Trojano, M, Grand'Maison, F, Gomez, J Antonio C, Izquierdo, G, Duquette, P, Girard, M, Grammond, P, Oreja-Guevara, C, Hupperts, R, Bergamaschi, R, Boz, C, Giuliani, G, Van Pesch, Vincent, Iuliano, G, Fiol, M, Cristiano, E, Verheul, F, Saladino, M Laura, Slee, M, Barnett, M, Deri, N, Flechter, S, Vella, N, Shaw, C, Herbert, J, Moore, F, Petkovska-Boskova, T, Jokubaitis, V, Butzkueven, H, and MSBase study group
Abstract: Background: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) statusfor the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. Methods: In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. Results: A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). Conclusions: The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis
Published: 2012

125. Geographical Variations in Sex Ratio Trends over Time in Multiple Sclerosis

Author: Paul, F, Trojano, M, Lucchese, G, Graziano, G, Taylor, BV, Simpson, S, Lepore, V, Grand'Maison, F, Duquette, P, Izquierdo, G, Grammond, P, Amato, MP, Bergamaschi, R, Giuliani, G, Boz, C, Hupperts, R, Van Pesch, V, Lechner-Scott, J, Cristiano, E, Fiol, M, Oreja-Guevara, C, Laura Saladino, M, Verheul, F, Slee, M, Paolicelli, D, Tortorella, C, D'Onghia, M, Iaffaldano, P, Direnzo, V, Butzkueven, H, Paul, F, Trojano, M, Lucchese, G, Graziano, G, Taylor, BV, Simpson, S, Lepore, V, Grand'Maison, F, Duquette, P, Izquierdo, G, Grammond, P, Amato, MP, Bergamaschi, R, Giuliani, G, Boz, C, Hupperts, R, Van Pesch, V, Lechner-Scott, J, Cristiano, E, Fiol, M, Oreja-Guevara, C, Laura Saladino, M, Verheul, F, Slee, M, Paolicelli, D, Tortorella, C, D'Onghia, M, Iaffaldano, P, Direnzo, V, and Butzkueven, H
Abstract: BACKGROUND: A female/male (F/M) ratio increase over time in multiple sclerosis (MS) patients was demonstrated in many countries around the world. So far, a direct comparison of sex ratio time-trends among MS populations from different geographical areas was not carried out. OBJECTIVE: In this paper we assessed and compared sex ratio trends, over a 60-year span, in MS populations belonging to different latitudinal areas. METHODS: Data of a cohort of 15,996 (F = 11,290; M = 4,706) definite MS with birth years ranging from 1930 to 1989 were extracted from the international MSBase registry and the New Zealand MS database. Gender ratios were calculated by six decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the respective national registries of births. RESULTS: Adjusted sex ratios showed a significant increase from the first to the last decade in the whole MS sample (from 2.35 to 2.73; p = 0.03) and in the subgroups belonging to the areas between 83° N and 45° N (from 1.93 to 4.55; p<0.0001) and between 45° N to 35° N (from 1.46 to 2.30; p<0.05) latitude, while a sex ratio stability over time was found in the subgroup from areas between 12° S and 55° S latitude. The sex ratio increase mainly affected relapsing-remitting (RR) MS. CONCLUSIONS: Our results confirm a general sex ratio increase over time in RRMS and also demonstrate a latitudinal gradient of this increase. These findings add useful information for planning case-control studies aimed to explore sex-related factors responsible for MS development.
Published: 2012

126. Frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude

Author: Lechner-Scott, J., Spencer, B., de Malmanche, T., Attia, J., Fitzgerald, M., Trojano, M., Grand'Maison, F., Gomez, J. Antonio C., Izquierdo, G., Duquette, P., Girard, M., Grammond, P., Oreja-Guevara, C., Hupperts, R., Bergamaschi, P., Boz, C., Giuliani, G., van Pesch, V., Iuliano, G., Fiol, M., Cristiano, E., Verheul, F., Laura Saladino, M., Slee, M., Barnett, M., Deri, N., Flechter, S., Vella, N., Shaw, C., Herbert, J., Moore, F., Petkovska-Boskova, T., Jokubaitis, V., Butzkueven, H., Lechner-Scott, J., Spencer, B., de Malmanche, T., Attia, J., Fitzgerald, M., Trojano, M., Grand'Maison, F., Gomez, J. Antonio C., Izquierdo, G., Duquette, P., Girard, M., Grammond, P., Oreja-Guevara, C., Hupperts, R., Bergamaschi, P., Boz, C., Giuliani, G., van Pesch, V., Iuliano, G., Fiol, M., Cristiano, E., Verheul, F., Laura Saladino, M., Slee, M., Barnett, M., Deri, N., Flechter, S., Vella, N., Shaw, C., Herbert, J., Moore, F., Petkovska-Boskova, T., Jokubaitis, V., and Butzkueven, H.
Abstract: With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.
Published: 2011

127. Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

Author: Bahlo, M., Booth, D.R., Broadley, S.A., Brown, M.A., Foote, S.J., Griffiths, L.R., Kilpatrick, T.J., Lechner-Scott, J., Moscato, P., Perreau, V.M., Rubio, J.P., Scott, R.J., Stankovich, J., Stewart, G.J., Taylor, B.V., Wiley, J., Clarke, G., Cox, M.B., Csurhes, P.A., Danoy, P., Drysdale, K., Field, J., Greer, J.M., Guru, P., Hadler, J., McMorran, B.J., Jensen, C.J., Johnson, L.J., McCallum, R., Merriman, M., Merriman, T., Pryce, K., Tajouri, L., Wilkins, E.J., Browning, B.L., Browning, S.R., Perera, D., Broadley, S., Butzkueven, H., Carroll, W.M., Chapman, C., Kermode, A.G., Marriott, M., Mason, D., Heard, R.N., Pender, M.P., Slee, M., Tubridy, N., Willoughby, E., Bahlo, M., Booth, D.R., Broadley, S.A., Brown, M.A., Foote, S.J., Griffiths, L.R., Kilpatrick, T.J., Lechner-Scott, J., Moscato, P., Perreau, V.M., Rubio, J.P., Scott, R.J., Stankovich, J., Stewart, G.J., Taylor, B.V., Wiley, J., Clarke, G., Cox, M.B., Csurhes, P.A., Danoy, P., Drysdale, K., Field, J., Greer, J.M., Guru, P., Hadler, J., McMorran, B.J., Jensen, C.J., Johnson, L.J., McCallum, R., Merriman, M., Merriman, T., Pryce, K., Tajouri, L., Wilkins, E.J., Browning, B.L., Browning, S.R., Perera, D., Broadley, S., Butzkueven, H., Carroll, W.M., Chapman, C., Kermode, A.G., Marriott, M., Mason, D., Heard, R.N., Pender, M.P., Slee, M., Tubridy, N., and Willoughby, E.
Abstract: To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13–14 (rs703842, P = 5.4 times 10-11; rs10876994, P = 2.7 times 10-10; rs12368653, P = 1.0 times 10-7) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 times 10-7; rs1569723, P = 2.9 times 10-7). Both loci are also associated with other autoimmune diseases1, 2, 3, 4, 5. We also replicated several known MS associations (HLA-DR15, P = 7.0 times 10-184; CD58, P = 9.6 times 10-8; EVI5-RPL5, P = 2.5 times 10-6; IL2RA, P = 7.4 times 10-6; CLEC16A, P = 1.1 times 10-4; IL7R, P = 1.3 times 10-3; TYK2, P = 3.5 times 10-3) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).
Published: 2009

128. Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

Author: Bahlo, M, Booth, DR, Broadley, SA, Brown, MA, Foote, SJ, Griffiths, LR, Kilpatrick, TJ, Lechner-Scott, J, Moscato, P, Perreau, VM, Rubio, JP, Scott, RJ, Stankovich, J, Stewart, GJ, Taylor, BV, Wiley, J, Clarke, G, Cox, MB, Csurhes, PA, Danoy, P, Drysdale, K, Field, J, Greer, JM, Guru, P, Hadler, J, McMorran, BJ, Jensen, CJ, Johnson, LJ, McCallum, R, Merriman, M, Merriman, T, Pryce, K, Tajouri, L, Wilkins, EJ, Browning, BL, Browning, SR, Perera, D, Butzkueven, H, Carroll, WM, Chapman, C, Kermode, AG, Marriott, M, Mason, D, Heard, RN, Pender, MP, Slee, M, Tubridy, N, Willoughby, E, Bahlo, M, Booth, DR, Broadley, SA, Brown, MA, Foote, SJ, Griffiths, LR, Kilpatrick, TJ, Lechner-Scott, J, Moscato, P, Perreau, VM, Rubio, JP, Scott, RJ, Stankovich, J, Stewart, GJ, Taylor, BV, Wiley, J, Clarke, G, Cox, MB, Csurhes, PA, Danoy, P, Drysdale, K, Field, J, Greer, JM, Guru, P, Hadler, J, McMorran, BJ, Jensen, CJ, Johnson, LJ, McCallum, R, Merriman, M, Merriman, T, Pryce, K, Tajouri, L, Wilkins, EJ, Browning, BL, Browning, SR, Perera, D, Butzkueven, H, Carroll, WM, Chapman, C, Kermode, AG, Marriott, M, Mason, D, Heard, RN, Pender, MP, Slee, M, Tubridy, N, and Willoughby, E
Abstract: To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).
Published: 2009

129. EXPOSURE TO INTERFERON-β THERAPY IN EARLY PREGNANCY: A LITERATURE REVIEW OF PREGNANCY OUTCOMES IN WOMEN WITH MULTIPLE SCLEROSIS

Author: Hughes, S, primary, Spelman, T, additional, Gray, O, additional, Boz, C, additional, Trojano, M, additional, Zwanikken, C, additional, Lugaresi, A, additional, Izquierdo, J, additional, Duquette, P, additional, Girard, M, additional, Grand'Maison, F, additional, Grammond, P, additional, Oreja-Guevara, C, additional, Hupperts, R, additional, Petersen, T, additional, Bergamaschi, R, additional, Giuliani, G, additional, Lechner-Scott, J, additional, Barnett, M, additional, Edite Rio, M, additional, van Pesch, V, additional, Pia Amato, M, additional, Iuliano, G, additional, Fiol, M, additional, Slee, M, additional, Verheul, F, additional, Cristiano, E, additional, Fernández Bolaños, R, additional, Saladino, D, additional, Poehlau, M, additional, Deri, N, additional, Oleschko Arruda, W, additional, Cabrera-Gomez, J, additional, Paine, M, additional, Vella, N, additional, Herbert, J, additional, Skromne, E, additional, Savino, A, additional, Shaw, C, additional, Moore, F, additional, Vucic, S, additional, Petkovska-Boskova, T, additional, Vetere, S, additional, McDonnell, G, additional, Hawkins, S, additional, Kee, F, additional, and Butzkueven, H, additional
Published: 2012
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130. Fluctuations of MS births and UV-light exposure

Author: Verheul, F., primary, Smolders, J., additional, Trojano, M., additional, Lepore, V., additional, Zwanikken, C., additional, Amato, M. P., additional, Grand'Maison, F., additional, Butzkueven, H., additional, Marrosu, M., additional, Duquette, P., additional, Comi, G., additional, Izquierdo, G., additional, Grammond, P., additional, Lus, G., additional, Petersen, T., additional, Bergamaschi, R., additional, Giuliani, G., additional, Boz, C., additional, Coniglio, G., additional, Van Pesch, V., additional, Lechner-Scott, J., additional, Cavalla, P., additional, Granella, F., additional, Avolio, C., additional, Fiol, M., additional, Poehlau, D., additional, Saladino, M. L., additional, Gallo, P., additional, Deri, N., additional, Oleschko Arruda, W., additional, Paine, M., additional, Ferro, M., additional, Barnett, M., additional, Cabrera-Gomez, J. A., additional, Slee, M., additional, Moore, F., additional, Shaw, C., additional, Petkovska-Boskova, T., additional, Rutherford, M., additional, Engelsen, O., additional, Damoiseaux, J., additional, and Hupperts, R., additional
Published: 2012
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131. AGATA—Advanced GAmma Tracking Array

Author: Akkoyun, S., primary, Algora, A., additional, Alikhani, B., additional, Ameil, F., additional, de Angelis, G., additional, Arnold, L., additional, Astier, A., additional, Ataç, A., additional, Aubert, Y., additional, Aufranc, C., additional, Austin, A., additional, Aydin, S., additional, Azaiez, F., additional, Badoer, S., additional, Balabanski, D.L., additional, Barrientos, D., additional, Baulieu, G., additional, Baumann, R., additional, Bazzacco, D., additional, Beck, F.A., additional, Beck, T., additional, Bednarczyk, P., additional, Bellato, M., additional, Bentley, M.A., additional, Benzoni, G., additional, Berthier, R., additional, Berti, L., additional, Beunard, R., additional, Lo Bianco, G., additional, Birkenbach, B., additional, Bizzeti, P.G., additional, Bizzeti-Sona, A.M., additional, Le Blanc, F., additional, Blasco, J.M., additional, Blasi, N., additional, Bloor, D., additional, Boiano, C., additional, Borsato, M., additional, Bortolato, D., additional, Boston, A.J., additional, Boston, H.C., additional, Bourgault, P., additional, Boutachkov, P., additional, Bouty, A., additional, Bracco, A., additional, Brambilla, S., additional, Brawn, I.P., additional, Brondi, A., additional, Broussard, S., additional, Bruyneel, B., additional, Bucurescu, D., additional, Burrows, I., additional, Bürger, A., additional, Cabaret, S., additional, Cahan, B., additional, Calore, E., additional, Camera, F., additional, Capsoni, A., additional, Carrió, F., additional, Casati, G., additional, Castoldi, M., additional, Cederwall, B., additional, Cercus, J.-L., additional, Chambert, V., additional, El Chambit, M., additional, Chapman, R., additional, Charles, L., additional, Chavas, J., additional, Clément, E., additional, Cocconi, P., additional, Coelli, S., additional, Coleman-Smith, P.J., additional, Colombo, A., additional, Colosimo, S., additional, Commeaux, C., additional, Conventi, D., additional, Cooper, R.J., additional, Corsi, A., additional, Cortesi, A., additional, Costa, L., additional, Crespi, F.C.L., additional, Cresswell, J.R., additional, Cullen, D.M., additional, Curien, D., additional, Czermak, A., additional, Delbourg, D., additional, Depalo, R., additional, Descombes, T., additional, Désesquelles, P., additional, Detistov, P., additional, Diarra, C., additional, Didierjean, F., additional, Dimmock, M.R., additional, Doan, Q.T., additional, Domingo-Pardo, C., additional, Doncel, M., additional, Dorangeville, F., additional, Dosme, N., additional, Drouen, Y., additional, Duchêne, G., additional, Dulny, B., additional, Eberth, J., additional, Edelbruck, P., additional, Egea, J., additional, Engert, T., additional, Erduran, M.N., additional, Ertürk, S., additional, Fanin, C., additional, Fantinel, S., additional, Farnea, E., additional, Faul, T., additional, Filliger, M., additional, Filmer, F., additional, Finck, Ch., additional, de France, G., additional, Gadea, A., additional, Gast, W., additional, Geraci, A., additional, Gerl, J., additional, Gernhäuser, R., additional, Giannatiempo, A., additional, Giaz, A., additional, Gibelin, L., additional, Givechev, A., additional, Goel, N., additional, González, V., additional, Gottardo, A., additional, Grave, X., additional, Gre¸bosz, J., additional, Griffiths, R., additional, Grint, A.N., additional, Gros, P., additional, Guevara, L., additional, Gulmini, M., additional, Görgen, A., additional, Ha, H.T.M., additional, Habermann, T., additional, Harkness, L.J., additional, Harroch, H., additional, Hauschild, K., additional, He, C., additional, Hernández-Prieto, A., additional, Hervieu, B., additional, Hess, H., additional, Hüyük, T., additional, Ince, E., additional, Isocrate, R., additional, Jaworski, G., additional, Johnson, A., additional, Jolie, J., additional, Jones, P., additional, Jonson, B., additional, Joshi, P., additional, Judson, D.S., additional, Jungclaus, A., additional, Kaci, M., additional, Karkour, N., additional, Karolak, M., additional, Kaşkaş, A., additional, Kebbiri, M., additional, Kempley, R.S., additional, Khaplanov, A., additional, Klupp, S., additional, Kogimtzis, M., additional, Kojouharov, I., additional, Korichi, A., additional, Korten, W., additional, Kröll, Th., additional, Krücken, R., additional, Kurz, N., additional, Ky, B.Y., additional, Labiche, M., additional, Lafay, X., additional, Lavergne, L., additional, Lazarus, I.H., additional, Leboutelier, S., additional, Lefebvre, F., additional, Legay, E., additional, Legeard, L., additional, Lelli, F., additional, Lenzi, S.M., additional, Leoni, S., additional, Lermitage, A., additional, Lersch, D., additional, Leske, J., additional, Letts, S.C., additional, Lhenoret, S., additional, Lieder, R.M., additional, Linget, D., additional, Ljungvall, J., additional, Lopez-Martens, A., additional, Lotodé, A., additional, Lunardi, S., additional, Maj, A., additional, van der Marel, J., additional, Mariette, Y., additional, Marginean, N., additional, Marginean, R., additional, Maron, G., additional, Mather, A.R., additional, Me¸czyński, W., additional, Mendéz, V., additional, Medina, P., additional, Melon, B., additional, Menegazzo, R., additional, Mengoni, D., additional, Merchan, E., additional, Mihailescu, L., additional, Michelagnoli, C., additional, Mierzejewski, J., additional, Milechina, L., additional, Million, B., additional, Mitev, K., additional, Molini, P., additional, Montanari, D., additional, Moon, S., additional, Morbiducci, F., additional, Moro, R., additional, Morrall, P.S., additional, Möller, O., additional, Nannini, A., additional, Napoli, D.R., additional, Nelson, L., additional, Nespolo, M., additional, Ngo, V.L., additional, Nicoletto, M., additional, Nicolini, R., additional, Le Noa, Y., additional, Nolan, P.J., additional, Norman, M., additional, Nyberg, J., additional, Obertelli, A., additional, Olariu, A., additional, Orlandi, R., additional, Oxley, D.C., additional, Özben, C., additional, Ozille, M., additional, Oziol, C., additional, Pachoud, E., additional, Palacz, M., additional, Palin, J., additional, Pancin, J., additional, Parisel, C., additional, Pariset, P., additional, Pascovici, G., additional, Peghin, R., additional, Pellegri, L., additional, Perego, A., additional, Perrier, S., additional, Petcu, M., additional, Petkov, P., additional, Petrache, C., additional, Pierre, E., additional, Pietralla, N., additional, Pietri, S., additional, Pignanelli, M., additional, Piqueras, I., additional, Podolyak, Z., additional, Le Pouhalec, P., additional, Pouthas, J., additional, Pugnére, D., additional, Pucknell, V.F.E., additional, Pullia, A., additional, Quintana, B., additional, Raine, R., additional, Rainovski, G., additional, Ramina, L., additional, Rampazzo, G., additional, La Rana, G., additional, Rebeschini, M., additional, Recchia, F., additional, Redon, N., additional, Reese, M., additional, Reiter, P., additional, Regan, P.H., additional, Riboldi, S., additional, Richer, M., additional, Rigato, M., additional, Rigby, S., additional, Ripamonti, G., additional, Robinson, A.P., additional, Robin, J., additional, Roccaz, J., additional, Ropert, J.-A., additional, Rossé, B., additional, Rossi Alvarez, C., additional, Rosso, D., additional, Rubio, B., additional, Rudolph, D., additional, Saillant, F., additional, Şahin, E., additional, Salomon, F., additional, Salsac, M.-D., additional, Salt, J., additional, Salvato, G., additional, Sampson, J., additional, Sanchis, E., additional, Santos, C., additional, Schaffner, H., additional, Schlarb, M., additional, Scraggs, D.P., additional, Seddon, D., additional, Şenyiğit, M., additional, Sigward, M.-H., additional, Simpson, G., additional, Simpson, J., additional, Slee, M., additional, Smith, J.F., additional, Sona, P., additional, Sowicki, B., additional, Spolaore, P., additional, Stahl, C., additional, Stanios, T., additional, Stefanova, E., additional, Stézowski, O., additional, Strachan, J., additional, Suliman, G., additional, Söderström, P.-A., additional, Tain, J.L., additional, Tanguy, S., additional, Tashenov, S., additional, Theisen, Ch., additional, Thornhill, J., additional, Tomasi, F., additional, Toniolo, N., additional, Touzery, R., additional, Travers, B., additional, Triossi, A., additional, Tripon, M., additional, Tun-Lanoë, K.M.M., additional, Turcato, M., additional, Unsworth, C., additional, Ur, C.A., additional, Valiente-Dobon, J.J., additional, Vandone, V., additional, Vardaci, E., additional, Venturelli, R., additional, Veronese, F., additional, Veyssiere, Ch., additional, Viscione, E., additional, Wadsworth, R., additional, Walker, P.M., additional, Warr, N., additional, Weber, C., additional, Weisshaar, D., additional, Wells, D., additional, Wieland, O., additional, Wiens, A., additional, Wittwer, G., additional, Wollersheim, H.J., additional, Zocca, F., additional, Zamfir, N.V., additional, Zie¸bliński, M., additional, and Zucchiatti, A., additional
Published: 2012
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132. The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude

Author: Lechner-Scott, J, primary, Spencer, B, additional, de Malmanche, T, additional, Attia, J, additional, Fitzgerald, M, additional, Trojano, M, additional, Grand’Maison, F, additional, Gomez, J Antonio C, additional, Izquierdo, G, additional, Duquette, P, additional, Girard, M, additional, Grammond, P, additional, Oreja-Guevara, C, additional, Hupperts, R, additional, Bergamaschi, R, additional, Boz, C, additional, Giuliani, G, additional, van Pesch, V, additional, Iuliano, G, additional, Fiol, M, additional, Cristiano, E, additional, Verheul, F, additional, Saladino, M Laura, additional, Slee, M, additional, Barnett, M, additional, Deri, N, additional, Flechter, S, additional, Vella, N, additional, Shaw, C, additional, Herbert, J, additional, Moore, F, additional, Petkovska-Boskova, T, additional, Jokubaitis, V, additional, and Butzkueven, H, additional
Published: 2011
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133. A novel mitochondrial DNA deletion producing progressive external ophthalmoplegia associated with multiple sclerosis

Author: Slee, M., primary, Finkemeyer, J., additional, Krupa, M., additional, Raghupathi, R., additional, Gardner, J., additional, Blumbergs, P., additional, Agzarian, M., additional, and Thyagarajan, D., additional
Published: 2011
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134. Characterisation of an asymmetric AGATA detector

Author: Unsworth, C., primary, Boston, A. J., additional, Boston, H. C., additional, Colosimo, S., additional, Cresswell, J., additional, Dimmock, M. R., additional, Filmer, F., additional, Judson, D., additional, Moon, S., additional, Nolan, P. J., additional, Norman, M. J., additional, and Slee, M., additional
Published: 2009
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135. A Semiconductor-Based Positron Emission Tomography System

Author: Oxley, D. C., primary, Boston, A. J., additional, Boston, H. C., additional, Cresswell, J. R., additional, Grint, A. N., additional, Harkness, L. J., additional, Jones, M., additional, Judson, D. S., additional, Nolan, P. J., additional, Slee, M., additional, Unsworth, C., additional, Lazarus, I. H., additional, and Baharuth-Ram, K., additional
Published: 2009
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136. Multifocal motor neuropathy: The diagnostic spectrum and response to treatment

Author: Slee, M., primary, Selvan, A., additional, and Donaghy, M., additional
Published: 2007
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137. Relapsing encephalopathy with headache: an unusual presentation of isolated intracranial neurosarcoidosis

Author: Rudkin, A. K, primary, Wilcox, R. A, additional, Slee, M., additional, Kupa, A., additional, and Thyagarajan, D., additional
Published: 2006
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138. Status and Performance of an AGATA asymmetric detector.

Author: Boston, A. J., Dimmock, M. R., Unsworth, C., Boston, H. C., Cooper, R. J., Grint, A. N., Harkness, L. J., Lazarus, I. H., Jones, M., Nolan, P. J., Oxley, D. C., Simpson, J., and Slee, M.
Subjects: DETECTORS, SECURITY systems, SENSOR networks, PHYSICS instruments, GERMANIUM crystals
Abstract: High-resolution gamma-ray detectors based on high-purity germanium crystals (HPGe) are one of the key workhorses of experimental nuclear science. The technical development of such detector technology has been dramatic in recent years. Large volume, high-granularity, electrically segmented HPGe detectors have been realised and a methodology to improve position sensitivity using pulse-shape analysis coupled with the novel technique of gamma-ray tracking has been developed. Collaborations have been established in Europe (AGATA) [1] and the USA (GRETA/GRETINA) [2] to build gamma-ray tracking spectrometers. This paper discusses the performance of the first AGATA (Advanced GAmma Tracking Array) asymmetric detector that has been tested at the University of Liverpool. The use of a fully digital data acquisition system has allowed detector charge pulse shapes from a selection of well defined photon interaction positions to be analysed, yielding important information on the position sensitivity of the detector. [ABSTRACT FROM AUTHOR]
Published: 2009
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139. Performance of an AGATA asymmetric detector.

Author: Boston, A. J., Dimmock, M. R., Unsworth, C., Boston, H. C., Cooper, R. J., Grint, A. N., Harkness, L. J., Lazarus, I. H., Jones, M., Nolan, P. J., Oxley, D. C., Simpson, J., and Slee, M.
Subjects: GAMMA rays, SPECTRUM analysis, GERMANIUM crystals, PHOTONS, ELECTROMAGNETIC waves
Abstract: Each major technical advance in gamma-ray detection devices has resulted in significant new insights into the structure of atomic nuclei. The next major step in gamma-ray spectroscopy involves achieving the goal of a 4π ball of germanium detectors by using the technique of gamma-ray energy tracking in electrically segmented germanium crystals. The resulting spectrometer will have an unparalleled level of detection power for nuclear electromagnetic radiation. Collaborations have been established in Europe (AGATA) [1] and the USA (GRETA/GRETINA) [2] to build gamma-ray tracking spectrometers. This paper discusses the performance of the first AGATA (Advanced GAmma Tracking Array) asymmetric detector that has been tested at the University of Liverpool. The use of a fully digital data acquisition system has allowed detector charge pulse shapes from a selection of well defined photon interaction positions to be analysed, yielding important information on the position sensitivity of the detector. [ABSTRACT FROM AUTHOR]
Published: 2008
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140. Pollination and fruit-set of Grevillea robusta in western Kenya

Author: Kalinganire, A., primary, Harwood, C. E., additional, Slee, M. U., additional, and Simons, A. J., additional
Published: 2001
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141. Factors influencing adherence in adolescents with asthma

Author: Van Es, S. M., primary, Bouter, L. M., additional, Kaptein, A. A., additional, Roorda, R. J., additional, Slee, M. A. C., additional, and Verweij, H., additional
Published: 1995
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142. Pollination Investigations for Production of the Hybrid between Slash and Caribbean Pines

Author: Slee, M. U., primary and Abbott, D. C., additional
Published: 1990
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143. Utilisation of disease modifying treatment and diversity of treatment pathways in Relapsing Remitting Multiple Sclerosis

Author: Hillen, J, Ward, M, Slee, M, Stanford, T, Roughead, E, Kalisch Ellett, L, and Pratt, N
Abstract: •Utilisation studies inform safe and effective medicines use.•The Australian market was responsive to 13 new medicines over 14 years.•Incidence and prevalence use increased by 20% and 88% respectively.•Diverse treatment pathways were found with exposure to multiple medicines over time.•Findings can contribute to developing post market surveillance studies.
Published: 2021
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144. Pregnancy incidence and therapy exposure in relapsing forms of MS: a 12-year retrospective multicentre analysis

Author: Jokubaitis, V. G., Havrdova, E., Horakova, D., Izquierdo, G., Kalincik, T., Walt, A., Nguyen, A. -L, Terzi, M., Alroughani, R., Duquette, P., Girard, M., Prat, A., Boz, C., Sola, P., Lugaresi, A., Lechner-Scott, J., Barnett, M., Grand Maison, F., Grammond, P., Ramo, C., Turkoglu, R., Mccombe, P., Hupperts, R., Bolanos, R. Fernandez, Pucci, E., Trojano, M., Granella, F., Spitaleri, D., Pesch, V., Soysal, A., Eva Kubala Havrdova, Verheul, F., Vucic, S., Hodgkinson, S., Slee, M., Ampapa, R., Prevost, J., Menoyo, J. L. Sanchez, Skibina, O., Iuliano, G., Solaro, C., Olascoaga, J., Shaw, C., Madsen, K., Naidoo, K., Hyde, R., and Butzkueven, H.

145. The risk of relapse following on-treatment clinically silent lesions in patients with relapsing-remitting multiple sclerosis

Author: Brown, J. W. L., Lugaresi, A., Horakova, D., Havrdova, E., Jokubaitis, V., Lechner-Scott, J., Trojano, M., Min, M., Shaw, C., Shuey, N., Slee, M., Mccombe, P., Pesch, V., Wijmeersch, B., Prevost, J., Moore, F., Prat, A., Girard, M., Duquette, P., Ayrignac, X., Sempere, A. Perez, Sanchez-Menoyo, J. L., Cristina Ramo-Tello, Csepany, T., Hutchinson, M., Luca, G., Bergamaschi, R., Granella, F., Curti, E., Tsantes, E., Sola, P., Ferraro, D., Alroughani, R., Hupperts, R., Al-Harbi, T., Sidhom, Y., Boz, C., Terzi, M., Ozakbas, S., Soysal, A., Pucci, E., Izquierdo, G., Iuliano, G., Rio, M. Edite, Spitaleri, D., Grammond, P., Grand Maison, F., Butzkueven, H., and Kalincik, T.

146. Determinants of MS re-activation after discontinuing therapies

Author: Husin, H., Wallace, J., Malpas, C., Sharmin, S., Horakova, D., Havrdova, E. Kubala, Izquierdo, G., Eichau, S., Prat, A., Girard, M., Duquette, P., Trojano, M., Grammond, P., Lugaresi, A., Onofrj, M., Ozakbas, S., Butzkueven, H., Sola, P., Ferraro, D., Alroughani, R., Grand Maison, F., Terzi, M., Lechner-Scott, J., Boz, C., Hupperts, R., Shaygannejad, V., Bergamaschi, R., Pucci, E., Pesch, V., Hodgkinson, S., Mccombe, P., Granella, F., Slee, M., Wijmeersch, B., Karabudak, R., Prevost, J., Petersen, T., Spitaleri, D., Barnett, M., Solaro, C., Iuliano, G., Verheul, F., Ramo-Tello, C., Recai Turkoglu, Fernandez Bolanos, R., Butler, E., Macdonell, R., Soysal, A., Betancur, M. Moreno, and Kalincik, T.

147. Comparison of efficacy and persistence of first line fingolimod vs interferon-beta/glatiramer in the presence of prior disease activity

Author: Spelman, T., Izquierdo, G., Alroughani, R., Bolaos, R. F., Havrdova, E., Horaova, D., Eva Kubala Havrdova, Lechner-Scott, J., Slee, M., Barnett, M., Boz, C., Terzi, M., Grand Maison, F., Lugaresi, A., Trojano, M., Butzkueven, H., and Sbase Study Grp, M.

148. Aggressive form of multiple sclerosis can be predicted early after disease onset

Author: Malpas, C. B., Manouchehrinia, A., Sharmin, S., Izanne Roos, Horakova, D., Havrdova, E. K., Trojano, M., Izquierdo, G., Eichau, S., Bergamaschi, R., Sola, P., Ferraro, D., Lugaresi, A., Prat, A., Girard, M., Duquette, P., Grammond, P., Grand Maison, F., Ozakbas, S., Pesch, V., Granella, F., Hupperts, R., Pucci, E., Boz, C., Iuliano, G., Sidhom, Y., Gouider, R., Spitaleri, D., Butzkueven, H., Soysal, A., Petersen, T., Verheul, F., Karabudak, R., Turkoglu, R., Ramo-Tello, C., Terzi, M., Cristiano, E., Slee, M., Mccombe, P., Macdonell, R., Fragoso, Y., Olascoaga, J., Altintas, A., Olsson, T., Hillert, J., and Kalincik, T.

149. Determinants of therapeutic lag in relapsing multiple sclerosis

Author: Izanne Roos, Frascoli, F., Horakova, D., Havrdova, E. K., Trojano, M., Izquierdo, G., Eichau, S., Patti, F., Prat, A., Girard, M., Duquette, P., Onofr, M., Lugaresi, A., Grammond, P., Ozakbas, S., Sola, P., Ferraro, D., Bergamaschi, R., Cartechini, E., Sa, M. J., Boz, C., Grand Maison, F., Lechner-Scott, J., Terzi, M., Granella, F., Alroughani, R., Iuliano, G., Hupperts, R., Spitaleri, D., Pesch, V., Soysal, A., Prevost, J., Olascoaga, J., Aguera-Morales, E., Turkoglu, R., Slee, M., Ramo-Tello, C., Sidhom, Y., Gouider, R., Mccombe, P., Butzkueven, H., Malpas, C., and Kalincik, T.

150. Risk of secondary progressive multiple sclerosis: a longitudinal study

Author: Fambiatos, A., Jokubaitis, V., Spelman, T., Horakova, D., Havrdova, E., Trojano, M., Prat, A., Girard, M., Duquette, P., Lugaresi, A., Izquierdo, G., Grand Maison, F., Grammond, P., Sola, P., Ferraro, D., Alroughani, R., Terzi, M., Hupperts, R., Boz, C., Lechner-Scott, J., Pucci, E., Bergamaschi, R., Pesch, V., Ozakbas, S., Granella, F., Ramo, C., Recai Turkoglu, Iuliano, G., Spitaleri, D., Mccombe, P., Solaro, C., Slee, M., Fernandez-Bolanos, R., Ampapa, R., Soysal, A., Petersen, T., Sanchez-Menoyo, J. L., Verheul, F., Prevost, J., Sidhom, Y., Gouider, R., Wijmeersch, B., Vucic, S., Cristiano, E., Saladino, M. L., Deri, N., Barnett, M., Walt, A., Butzkueven, H., and Kalincik, T.

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