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133 results on '"Pottier, C"'

1. Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis

Author

Lefort, M., Sharmin, S., Andersen, J. B., Vukusic, S., Casey, R., Debouverie, M., Edan, G., Ciron, J., Ruet, A., De Sèze, J., Maillart, E., Zephir, H., Labauge, P., Defer, G., Lebrun-Frenay, C., Moreau, T., Berger, E., Clavelou, P., Pelletier, J., Stankoff, B., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Wahab, A., Camdessanché, J. P., Maurousset, A., Ben Nasr, H., Hankiewicz, K., Pottier, C., Maubeuge, N., Dimitri-Boulos, D., Nifle, C., Laplaud, D. A., Horakova, D., Havrdova, E. K., Alroughani, R., Izquierdo, G., Eichau, S., Ozakbas, S., Patti, F., Onofrj, M., Lugaresi, A., Terzi, M., Grammond, P., Grand’Maison, F., Yamout, B., Prat, A., Girard, M., Duquette, P., Boz, C., Trojano, M., McCombe, P., Slee, M., Lechner-Scott, J., Turkoglu, R., Sola, P., Ferraro, D., Granella, F., Shaygannejad, V., Prevost, J., Maimone, D., Skibina, O., Buzzard, K., Van der Walt, A., Karabudak, R., Van Wijmeersch, B., Csepany, T., Spitaleri, D., Vucic, S., Koch-Henriksen, N., Sellebjerg, F., Soerensen, P. S., Hilt Christensen, C. C., Rasmussen, P. V., Jensen, M. B., Frederiksen, J. L., Bramow, S., Mathiesen, H. K., Schreiber, K. I., Butzkueven, H., Magyari, M., Kalincik, T., and Leray, E.

Published
2022
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2. Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI

Author

Brochet, B., Casey, R., Cotton, F., De Sèze, J., Douek, P., Guillemin, F., Laplaud, D., Lebrun-Frenay, C., Mansuy, L., Moreau, T., Olaiz, J., Pelletier, J., Rigaud-Bully, C., Stankoff, B., Vukusic, S., Marignier, R., Debouverie, M., Edan, G., Ciron, J., Ruet, A., Collongues, N., Lubetzki, C., Vermersch, P., Labauge, P., Defer, G., Cohen, M., Fromont, A., Wiertlewsky, S., Berger, E., Clavelou, P., Audoin, B., Giannesini, C., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Créange, A., Camdessanché, J.-P., Faure, J., Maurousset, A., Patry, I., Hankiewicz, K., Pottier, C., Maubeuge, N., Labeyrie, C., Nifle, C., Ameli, R., Anxionnat, R., Attye, A., Bannier, E., Barillot, C., Ben Salem, D., Boncoeur-Martel, M.-P., Bonneville, F., Boutet, C., Brisset, J.-C., Cervenanski, F., Claise, B., Commowick, O., Constans, J.-M., Dardel, P., Desal, H., Dousset, Vincent, Durand-Dubief, F., Ferre, J.-C., Gerardin, E., Glattard, T., Grand, S., Grenier, T., Guillevin, R., Guttmann, C., Krainik, A., Kremer, S., Lion, S., Menjot de Champfleur, N., Mondot, L., Outteryck, O., Pyatigorskaya, N., Pruvo, J.-P., Rabaste, S., Ranjeva, J.-P., Roch, J.-A., Sadik, J.C., Sappey-Marinier, D., Savatovsky, J., Tanguy, J.-Y., Tourbah, A., Tourdias, T., Roca, P., Colas, L., Tucholka, A., Rubini, P., Cackowski, S., Ding, J., Budzik, J.-F., Renard, F., Doyle, S., Barbier, E.L., Bousaid, I., Lassau, N., and Verclytte, S.

Published
2020
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3. New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions

Author

Ameli, R., Anxionnat, R., Audoin, B., Attye, A., Bannier, E., Barillot, C., Ben Salem, D., Boncoeur-Martel, M.-P., Bonhomme, G., Bonneville, F., Boutet, C., Brisset, J.C., Cervenanski, F., Claise, B., Commowick, O., Constans, J.-M., Cotton, F., Dardel, P., Desal, H., Dousset, V., Durand-Dubief, F., Ferre, J.-C., Gaultier, A., Gerardin, E., Glattard, T., Grand, S., Grenier, T., Guillevin, R., Guttmann, C., Krainik, A., Kremer, S., Lion, S., Champfleur, N. Menjot De, Mondot, L., Outteryck, O., Pyatigorskaya, N., Pruvo, J.-P., Rabaste, S., Ranjeva, J.-P., Roch, J.-A., Sadik, J.-C., Sappey-Marinier, D., Savatovsky, J., Stankoff, B., Tanguy, J.-Y., Tourbah, A., Tourdias, T., Brochet, B., Casey, R., De Sèze, J., Douek, P., Guillemin, F., Laplaud, D., Lebrun-Frenay, C., Mansuy, L., Moreau, T., Olaiz, J., Pelletier, J., Rigaud-Bully, C., Vukusic, S., Debouverie, M., Edan, G., Ciron, J., Lubetzki, C., Vermersch, P., Labauge, P., Defer, G., Berger, E., Clavelou, P., Gout, O., Thouvenot, E., Heinzlef, O., Al-Khedr, A., Bourre, B., Casez, O., Cabre, P., Montcuquet, A., Créange, A., Camdessanché, J.-P., Bakchine, S., Maurousset, A., Patry, I., De Broucker, T., Pottier, C., Neau, J.-P., Labeyrie, C., Nifle, C., Brisset, Jean-Christophe, Kremer, Stephane, Hannoun, Salem, Bonneville, Fabrice, Durand-Dubief, Francoise, Tourdias, Thomas, Barillot, Christian, Guttmann, Charles, Vukusic, Sandra, Dousset, Vincent, and Cotton, Francois

Published
2020
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6. Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis

Author

Laplaud, David-Axel, Casey, Romain, Barbin, Laetitia, Debouverie, Marc, De Sèze, Jérôme, Brassat, David, Wiertlewski, Sandrine, Brochet, Bruno, Pelletier, Jean, Vermersch, Patrick, Edan, Gilles, Lebrun-Frenay, Christine, Clavelou, Pierre, Thouvenot, Eric, Camdessanché, Jean-Philippe, Tourbah, Ayman, Stankoff, Bruno, Al Khedr, Abdullatif, Cabre, Philippe, Lubetzki, Catherine, Papeix, Caroline, Berger, Eric, Heinzlef, Olivier, Debroucker, Thomas, Moreau, Thibault, Gout, Olivier, Bourre, Bertrand, Wahab, Abir, Labauge, Pierre, Magy, Laurent, Defer, Gilles, Guennoc, Anne-Marie, Maubeuge, Nicolas, Labeyrie, Céline, Patry, Ivania, Nifle, Chantal, Casez, Olivier, Michel, Laure, Rollot, Fabien, Leray, Emmanuelle, Vukusic, Sandra, Foucher, Yohann, Fontaine, B., Marignier, R., Durand-Dubief, F., Mathey, G., Le Page, E., Peaureaux-Averseng, D., Ouallet, J.C., Ruet, A., Collongues, N., Hautecoeur, P., Zephir, H., Maillard, E., Cohen, M., Derache, N., Branger, P., Ayrignac, X., Carra-Dalliere, C., Fromont, A., Chamard-Witkowski, L., Taithe, F., Moisset, X., Audoin, B., Rico-Lamy, A., Castelnovo, G., Giannesini, C., Fagniez, O., Bensa, C., Gueguen, A., Kasonde, I. Tabellah, De Vilmarest, A., Montcuquet, A., Vaillants, M., Beltran, S., Creange, A., Ayache, S., Abdellaoui, M., Pottier, C., Slesari, I., Deburghraeve, V., Neau, J.P., Servan, J., Pico, F., Henry, C., and Hankiewicz, K.

Published
2019
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8. Developing digital twins of multi-camera metrology systems in Blender.

Author

Pottier, C, Petzing, J, Eghtedari, F, Lohse, N, and Kinnell, P

Subjects
DIGITAL twins, METROLOGY, SURFACE texture, CAMERAS, DIGITAL cameras, 3-D animation
Abstract

Blender is an open-source three-dimensional animation software, which can be used as a simulation tool in metrology, to build numerical models that can be used in the design and optimisation of camera-based measurement systems. In this work, the relevance of using Blender to model camera-based measurement systems was explored. Two experiments were conducted in real-world and Blender modelled environments, one using individual cameras for a simple measurement task, the other considering multi-camera position optimisation. The objective was to verify whether the virtual cameras created in Blender can perceive and measure objects in the same manner as the real cameras in an equivalent environment. The results demonstrate that in its native modelling format Blender satisfies the optical metrology characteristics of measurement, but the correlation between Blender output and real-world results is highly sensitive to initial modelling parameters such as illumination intensity, camera definitions and object surface texture. [ABSTRACT FROM AUTHOR]

Published
2023
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12. LifeTime and improving European healthcare through cell-based interceptive medicine

Author

Rajewsky, N., Almouzni, G., Gorski, S., Aerts, S., Amit, I., Bertero, M., Bock, C., Bredenoord, A., Cavalli, G., Chiocca, S., Clevers, H., Strooper, B., Eggert, A., Ellenberg, J., Fernández, X., Figlerowicz, M., Gasser, S., Hubner, N., Kjems, J., Knoblich, J., Krabbe, G., Lichter, P., Linnarsson, S., Marine, J., Marioni, J., Marti-Renom, M., Netea, M., Nickel, D., Nollmann, M., Novak, H., Parkinson, H., Piccolo, S., Pinheiro, I., Pombo, A., Popp, C., Reik, W., Roman-Roman, S., Rosenstiel, P., Schultze, J., Stegle, O., Tanay, A., Testa, G., Thanos, D., Theis, F., Torres-Padilla, M., Valencia, A., Vallot, C., van Oudenaarden, A., Vidal, M., Voet, T., Alberi, L., Alexander, S., Alexandrov, T., Arenas, E., Bagni, C., Balderas, R., Bandelli, A., Becher, B., Becker, M., Beerenwinkel, N., Benkirame, M., Beyer, M., Bickmore, W., Biessen, E., Blomberg, N., Blumcke, I., Bodenmiller, B., Borroni, B., Boumpas, D., Bourgeron, T., Bowers, S., Braeken, D., Brooksbank, C., Brose, N., Bruining, H., Bury, J., Caporale, N., Cattoretti, G., Chabane, N., Chneiweiss, H., Cook, S., Curatolo, P., de Jonge, M., Deplancke, B., de Witte, P., Dimmeler, S., Draganski, B., Drews, A., Dumbrava, C., Engelhardt, S., Gasser, T., Giamarellos-Bourboulis, E., Graff, C., Grün, D., Gut, I., Hansson, O., Henshall, D., Herland, A., Heutink, P., Heymans, S., Heyn, H., Huch, M., Huitinga, I., Jackowiak, P., Jongsma, K., Journot, L., Junker, J., Katz, S., Kehren, J., Kempa, S., Kirchhof, P., Klein, C., Koralewska, N., Korbel, J., Kühnemund, M., Lamond, A., Lauwers, E., Le Ber, I., Leinonen, V., Tobon, A., Lundberg, E., Lunkes, A., Maatz, H., Mann, M., Marelli, L., Matser, V., Matthews, P., Mechta-Grigoriou, F., Menon, R., Nielsen, A., Pagani, M., Pasterkamp, R., Pitkänen, A., Popescu, V., Pottier, C., Puisieux, A., Rademakers, R., Reiling, D., Reiner, O., Remondini, D., Ritchie, C., Rohrer, J., Saliba, A., Sanchez-Valle, R., Santosuosso, A., Sauter, A., Scheltema, R., Scheltens, P., Schiller, H., Schneider, A., Seibler, P., Sheehan-Rooney, K., Shields, D., Sleegers, K., Smit, A., Smith, K., Smolders, I., Synofzik, M., Tam, W., Teichmann, S., Thom, M., Turco, M., van Beusekom, H., Vandenberghe, R., den Hoecke, S., de Poel, I., van der Ven, A., van der Zee, J., van Lunzen, J., van Minnebruggen, G., Paesschen, W., van Swieten, J., van Vught, R., Verhage, M., Verstreken, P., Villa, C., Vogel, J., von Kalle, C., Walter, J., Weckhuysen, S., Weichert, W., Wood, L., Ziegler, A., Zipp, F., HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., Medical Research Council (MRC), UK DRI Ltd, TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany., Barcelona Supercomputing Center, LifeTime Community Working Groups, Cardiology, Neurology, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, Rajewsky N., Almouzni G., Gorski S.A., Aerts S., Amit I., Bertero M.G., Bock C., Bredenoord A.L., Cavalli G., Chiocca S., Clevers H., De Strooper B., Eggert A., Ellenberg J., Fernandez X.M., Figlerowicz M., Gasser S.M., Hubner N., Kjems J., Knoblich J.A., Krabbe G., Lichter P., Linnarsson S., Marine J.-C., Marioni J.C., Marti-Renom M.A., Netea M.G., Nickel D., Nollmann M., Novak H.R., Parkinson H., Piccolo S., Pinheiro I., Pombo A., Popp C., Reik W., Roman-Roman S., Rosenstiel P., Schultze J.L., Stegle O., Tanay A., Testa G., Thanos D., Theis F.J., Torres-Padilla M.-E., Valencia A., Vallot C., van Oudenaarden A., Vidal M., Voet T., Alberi L., Alexander S., Alexandrov T., Arenas E., Bagni C., Balderas R., Bandelli A., Becher B., Becker M., Beerenwinkel N., Benkirame M., Beyer M., Bickmore W., Biessen E.E.A.L., Blomberg N., Blumcke I., Bodenmiller B., Borroni B., Boumpas D.T., Bourgeron T., Bowers S., Braeken D., Brooksbank C., Brose N., Bruining H., Bury J., Caporale N., Cattoretti G., Chabane N., Chneiweiss H., Cook S.A., Curatolo P., de Jonge M.I., Deplancke B., de Witte P., Dimmeler S., Draganski B., Drews A., Dumbrava C., Engelhardt S., Gasser T., Giamarellos-Bourboulis E.J., Graff C., Grun D., Gut I., Hansson O., Henshall D.C., Herland A., Heutink P., Heymans S.R.B., Heyn H., Huch M., Huitinga I., Jackowiak P., Jongsma K.R., Journot L., Junker J.P., Katz S., Kehren J., Kempa S., Kirchhof P., Klein C., Koralewska N., Korbel J.O., Kuhnemund M., Lamond A.I., Lauwers E., Le Ber I., Leinonen V., Tobon A.L., Lundberg E., Lunkes A., Maatz H., Mann M., Marelli L., Matser V., Matthews P.M., Mechta-Grigoriou F., Menon R., Nielsen A.F., Pagani M., Pasterkamp R.J., Pitkanen A., Popescu V., Pottier C., Puisieux A., Rademakers R., Reiling D., Reiner O., Remondini D., Ritchie C., Rohrer J.D., Saliba A.-E., Sanchez-Valle R., Santosuosso A., Sauter A., Scheltema R.A., Scheltens P., Schiller H.B., Schneider A., Seibler P., Sheehan-Rooney K., Shields D., Sleegers K., Smit A.B., Smith K.G.C., Smolders I., Synofzik M., Tam W.L., Teichmann S., Thom M., Turco M.Y., van Beusekom H.M.M., Vandenberghe R., Van den Hoecke S., Van de Poel I., van der Ven A., van der Zee J., van Lunzen J., van Minnebruggen G., Van Paesschen W., van Swieten J., van Vught R., Verhage M., Verstreken P., Villa C.E., Vogel J., von Kalle C., Walter J., Weckhuysen S., Weichert W., Wood L., Ziegler A.-G., Zipp F., Center for Neurogenomics and Cognitive Research, Functional Genomics, Rajewsky, N, Almouzni, G, Gorski, S, Aerts, S, Amit, I, Bertero, M, Bock, C, Bredenoord, A, Cavalli, G, Chiocca, S, Clevers, H, De Strooper, B, Eggert, A, Ellenberg, J, Fernández, X, Figlerowicz, M, Gasser, S, Hubner, N, Kjems, J, Knoblich, J, Krabbe, G, Lichter, P, Linnarsson, S, Marine, J, Marioni, J, Marti-Renom, M, Netea, M, Nickel, D, Nollmann, M, Novak, H, Parkinson, H, Piccolo, S, Pinheiro, I, Pombo, A, Popp, C, Reik, W, Roman-Roman, S, Rosenstiel, P, Schultze, J, Stegle, O, Tanay, A, Testa, G, Thanos, D, Theis, F, Torres-Padilla, M, Valencia, A, Vallot, C, van Oudenaarden, A, Vidal, M, Voet, T, Cattoretti, G, Alliance for Modulation in Epilepsy, Pharmaceutical and Pharmacological Sciences, Experimental Pharmacology, RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Spec Cardiologie (9), and Cardiologie

Subjects
0301 basic medicine, Male, Artificial intelligence, Legislation, Medical, [SDV]Life Sciences [q-bio], Molecular datasets, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Cell- and Tissue-Based Therapy, Diseases, LifeTime Community Working Groups, Disease, Biomarkers, Systems biology, Health data, Pharmacology, Toxicology and Pharmaceutics(all), 0302 clinical medicine, Conjunts de dades, ethics [Delivery of Health Care], Health care, Pathology, Medicine, European healthcare, BRAIN, Single-cell multi-omics, GENE-EXPRESSION, Multidisciplinary, methods [Medicine], Education, Medical, Settore BIO/13, Intel.ligència artificial, 3. Good health, ALZHEIMERS-DISEASE, Europe, Health, Management system, Perspective, Female, ddc:500, Single-Cell Analysis, Biomarkers, Diseases, Systems biology, Complex diseases, Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], medicine.medical_specialty, General Science & Technology, Cells, MEDLINE, cell-based interceptive medicine, LifeTime Initiative, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Clinical datasets, Artificial Intelligence, REVEALS, LifeTime Community, standards [Medicine], Humans, OMICS, RECONSTRUCTION, Intensive care medicine, trends [Medicine], trends [Delivery of Health Care], business.industry, Disease progression, standards [Delivery of Health Care], methods [Delivery of Health Care], 030104 developmental biology, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], single cell, personalized therapy, machine learning, bioinformatics, systems biology, disease, cell-based interceptive medicine, Early Diagnosis, Cardiovascular and Metabolic Diseases, Human medicine, business, Delivery of Health Care, 030217 neurology & neurosurgery, Cell based
Abstract

Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade., The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe.

Published
2020
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15. Publisher Correction: LifeTime and improving European healthcare through cell-based interceptive medicine (Nature, (2020), 587, 7834, (377-386), 10.1038/s41586-020-2715-9)

Author

Rajewsky, N. Almouzni, G. Gorski, S.A. Aerts, S. Amit, I. Bertero, M.G. Bock, C. Bredenoord, A.L. Cavalli, G. Chiocca, S. Clevers, H. De Strooper, B. Eggert, A. Ellenberg, J. Fernández, X.M. Figlerowicz, M. Gasser, S.M. Hubner, N. Kjems, J. Knoblich, J.A. Krabbe, G. Lichter, P. Linnarsson, S. Marine, J.-C. Marioni, J.C. Marti-Renom, M.A. Netea, M.G. Nickel, D. Nollmann, M. Novak, H.R. Parkinson, H. Piccolo, S. Pinheiro, I. Pombo, A. Popp, C. Reik, W. Roman-Roman, S. Rosenstiel, P. Schultze, J.L. Stegle, O. Tanay, A. Testa, G. Thanos, D. Theis, F.J. Torres-Padilla, M.-E. Valencia, A. Vallot, C. van Oudenaarden, A. Vidal, M. Voet, T. Alberi, L. Alexander, S. Alexandrov, T. Arenas, E. Bagni, C. Balderas, R. Bandelli, A. Becher, B. Becker, M. Beerenwinkel, N. Benkirane, M. Beyer, M. Bickmore, W.A. Biessen, E.E.A.L. Blomberg, N. Blumcke, I. Bodenmiller, B. Borroni, B. Boumpas, D.T. Bourgeron, T. Bowers, S. Braeken, D. Brooksbank, C. Brose, N. Bruining, H. Bury, J. Caporale, N. Cattoretti, G. Chabane, N. Chneiweiss, H. Cook, S.A. Curatolo, P. de Jonge, M.I. Deplancke, B. de Witte, P. Dimmeler, S. Draganski, B. Drews, A. Dumbrava, C. Engelhardt, S. Gasser, T. Giamarellos-Bourboulis, E.J. Graff, C. Grün, D. Gut, I.G. Hansson, O. Henshall, D.C. Herland, A. Heutink, P. Heymans, S.R.B. Heyn, H. Huch, M. Huitinga, I. Jackowiak, P. Jongsma, K.R. Journot, L. Junker, J.P. Katz, S. Kehren, J. Kempa, S. Kirchhof, P. Klein, C. Koralewska, N. Korbel, J.O. Kühnemund, M. Lamond, A.I. Lauwers, E. Le Ber, I. Leinonen, V. López-Tobón, A. Lundberg, E. Lunkes, A. Maatz, H. Mann, M. Marelli, L. Matser, V. Matthews, P.M. Mechta-Grigoriou, F. Menon, R. Nielsen, A.F. Pagani, M. Pasterkamp, R.J. Pitkänen, A. Popescu, V. Pottier, C. Puisieux, A. Rademakers, R. Reiling, D. Reiner, O. Remondini, D. Ritchie, C. Rohrer, J.D. Saliba, A.-E. Sanchez-Valle, R. Santosuosso, A. Sauter, A. Scheltema, R.A. Scheltens, P. Schiller, H.B. Schneider, A. Seibler, P. Sheehan-Rooney, K. Shields, D.J. Sleegers, K. Smit, A.B. Smith, K.G.C. Smolders, I. Synofzik, M. Tam, W.L. Teichmann, S.A. Thom, M. Turco, M.Y. van Beusekom, H.M.M. Vandenberghe, R. Van den Hoecke, S. van de Poel, I. van der Ven, A. van der Zee, J. van Lunzen, J. van Minnebruggen, G. van Oudenaarden, A. Van Paesschen, W. van Swieten, J.C. van Vught, R. Verhage, M. Verstreken, P. Villa, C.E. Vogel, J. von Kalle, C. Walter, J. Weckhuysen, S. Weichert, W. Wood, L. Ziegler, A.-G. Zipp, F. LifeTime Community Working Groups

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
Abstract

In this Perspective, owing to an error in the HTML, the surname of author Alejandro López-Tobón of the LifeTime Community Working Groups consortium was indexed as ‘Tobon’ rather than ‘López-Tobón’ and the accents were missing. The HTML version of the original Perspective has been corrected; the PDF and print versions were always correct. © 2021, The Author(s).

Published
2021

19. Chapter 10 Trajectories of Urbanism in the Angkorian World

Author

Evans, Damian, Fletcher, Roland, Klassen, Sarah, pottier, christophe, and Wijker, Pelle

Subjects
Angkorian, Asia, bic Book Industry Communication::H Humanities::HD Archaeology
Abstract

The Angkorian World explores the history of Southeast Asia’s largest ancient state from the first to mid-second millennium CE. Chapters by leading scholars combine evidence from archaeology, texts, and the natural sciences to introduce the Angkorian state, describe its structure, and explain its persistence over more than six centuries. Comprehensive and accessible, this book will be an indispensable resource for anyone studying premodern Asia. The volume’s first of six sections provides historical and environmental contexts and discusses data sources and the nature of knowledge production. The next three sections examine the anthropogenic landscapes of Angkor (agrarian, urban, and hydraulic), the state institutions that shaped the Angkorian state, and the economic foundations on which Angkor operated. Part V explores Angkorian ideologies and realities, from religion and nation to identity. The volume’s last part reviews political and aesthetic Angkorian legacies in an effort to explain why the idea of Angkor remains central to its Cambodian descendants. Maps, graphics, and photographs guide readers through the content of each chapter. Chapters in this volume synthesise more than a century of work at Angkor and in the regions it influenced. The Angkorian World will satisfy students, researchers, academics, and the knowledgeable layperson who seeks to understand how this great Angkorian Empire arose and functioned in the premodern world.

Published
2023
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20. Comparison of two remote sensing methods for the evaluation of ocean dynamics

Author

Sudre, J., Pont, Oriol, Pottier, C., Yahia, H., Garcon, Veronique, Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), DYNBIO LEGOS, Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Geometry and Statistics in acquisition data (GeoStat), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre National d’Études Spatiales [Paris] (CNES), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
[INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract

International audience; The dynamics of the ocean flow are governed by the cascade process where the energy is injected in the system at the largest scale and dissipated at viscous scale. In between, the energy crosses all the intermediary scales and is responsible for the creation of oceanographic structures at different scales. To obtain the motion field of ocean dynamics [1] at the high resolution of Sea Surface Temperature (SST) Modis data (spatial resolution : 4 km) using one single image, we associate the Microcanonical Multiscale Formalism (MMF) [2] and the Microcanonical Cascade (MC) which represent these processes where the energy is transferred from scale to scale [3]. To link two different scales (or, in a remote sensing context, the same image at two different resolutions), the MC requires the exact determination of an optimal wavelet which separates completely the Multiscale Operator and the wavelet transform at the highest resolution. This exact determination of the optimal wavelet for a given dataset is difficult and there is no systematic algorithm to find it. Our goal is to best approximate the optimal wavelet for SST data by using Q-test [4]. References [1] H. Yahia, J. Sudre, C. Pottier and V. Garçon, 2010, Motion analysis in oceanographic satellite images using multiscale methods and the energy cascade, Pattern Recognition, DOI: 10.1016/J.patcog.2010.04.011 [2] A. Turiel, H. Yahia and C. Perez-Vicente, 2008 Microcanonical Multifractal Formalism: a geometrical approach to multifractal systems. Part I: Singularity Analysis, Journal of Physics A 41:015501. [3] C. Pottier, A. Turiel, V. Garçon, 2008, Inferring missing data in satellite chlorophyll maps using turbulent cascading, Remote Sensing of Environment, 112,4242-4260, 10.1016/j.rse.2008.07.010 [4] O. Pont, A Microcanonical cascade formalism for multifractal systems ans its application to data inference and forecasting. PhD thesis, Dept. of Fundamental Physics, University of Barcelona, 2009

Published
2010

21. Evidencing of multiplicative cascading and intermittency in real/synthetic oceanographic signals: application to the evaluation of ocean dynamics

Author

Sudre, J., Pont, Oriol, Pottier, C., Yahia, H., Garcon, Veronique, Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), DYNBIO LEGOS, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Geometry and Statistics in acquisition data (GeoStat), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre National d’Études Spatiales [Paris] (CNES), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), and Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
[SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere
Abstract

International audience; Most existing methods in analyzing motion in Computer Vision do not take into account key features of ocean dynamics: turbulence and intermittency, which contribute importantly to the shape and motion of observed and acquired coherent structures. Besides, the specificities of these remotely sensed acquisitions (Sea Surface Temperature, chlorophyll a concentration) lead to question the pertinence of existing Computer Vision approaches to analyze motion in these types of image sequences. To compute the motion field at high resolution associating the Microcanonical Multiscale Formalism (MMF) [1] and the Microcanonical Cascade (MC) [2], one needs to give prominence to the intermittency and cascade properties observed in SST Modis data and/or synthetic signals from an ocean model. We propose here to evaluate the ocean dynamics with respect to intermittency/cascading properties evaluation for data acquired by satellites or synthetic data coming from a simulation model. We then apply the combination of MMF and MC to obtain high resolution (4km) motion fields [3]. References [1] A. Turiel, H. Yahia and C. Perez-Vicente, 2008 Microcanonical Multifractal Formalism: a geometrical approach to multifractal systems. Part I: Singularity Analysis Journal of Physics A 41:015501. [2] C. Pottier, A. Turiel, V. Garçon, 2008, Inferring missing data in satellite chlorophyll maps using turbulent cascading, Remote Sensing of Environnement, 112,4242-4260, 10.1016/j.rse.2008.07.010 [3] H. Yahia, J. Sudre, C. Pottier and V. Garçon, 2010, Motion analysis in oceanographic satellite images using multiscale methods and the energy cascade, Pattern Recognition, DOI: 10.1016/J.patcog.2010.04.011

Published
2010

22. Inferring fluid motion at submesoscale from high resolution remotely sensed data

Author

Sudre, J., Yahia, H., Pottier, C., Garcon, Veronique, Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), DYNBIO LEGOS, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Geometry and Statistics in acquisition data (GeoStat), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre National d’Études Spatiales [Paris] (CNES), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), and Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
[INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract

http://ifisc.uib-csic.es/orflow10/; International audience

Published
2010

23. Determination of geostrophic vector field on high resolution SST images from the energy cascade

Author

Yahia, H., Sudre, J., Pottier, C., Garcon, V., Geometry and Statistics in acquisition data (GeoStat), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), DYNBIO LEGOS, Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
[INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2009

26. Biomechanical findings in rats undergoing fascial reconstruction with graft materials suggested as an alternative to polypropylene.

Author

Konstantinovic, M.L., Ozog, Y., Spelzini, F., Pottier, C., De Ridder, D., and Deprest, J.

Abstract

Aims Graft materials used for pelvic floor reinforcement should still be considered as investigational and, therefore, evaluated experimentally and within clinical trials. The present report describes our biomechanical findings in rats implanted with selected novel implant materials, which in recent years have been suggested as alternatives to plain polypropylene (PP) meshes. Methods Full thickness abdominal wall defects were primarily repaired by the implant of interest. Experiments involved eight different implant materials: two partly degradable synthetic implants, that is, a hybrid of polyglactin 910 with PP (Vypro II) and collagen coated PP (Pelvitex); two non-cross linked (Surgisis, InteXēn LP) and two cross-linked materials (Pelvicol, Pelvisoft) and two porous modifications of InteXēn LP and Pelvicol implants. At different time points (7, 14, 30, and 90 days), the implants and surrounding host tissue (explant) were harvested and tensiometry was performed. Tensile strength and location of breakage were recorded. Results In general resorbable non-cross linked collagen matrices and porous materials were weaker after 90 days; similar behavior was seen for implant materials alone and their construction with the surrounding native tissue. Both non-porous and porous modification of InteXēn LP appeared at 90 days as a very thin layer of collagen that was two-thirds, respectively one-third of the initial thickness. Conclusions In experimental conditions, sufficient strength was obtained only after 3 months, and PP containing constructs appeared as the strongest though reconstruction with Pelvicol showed comparable outcomes. Lower values for strength of non-cross linked and porous collagen materials are questioning their efficacy for pelvic floor reconstruction. Neurourol. Urodynam. 29:488-493, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Published
2010
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29. P.17.15 Life-threatening lactic acidosis occurring in adults with rare mutations of mtDNA: About three cases.

Author

Pottier, C., Behin, A., Gilleron, M., Sharshar, T., Lombes, A., Jardel, C., and Eymard, B.

Subjects
*LACTIC acidosis, *GENETIC mutation, *MITOCHONDRIAL DNA, *METABOLIC disorders, *MITOCHONDRIAL pathology, DISEASES in adults
Abstract

To report three observations of life-threatening lactic acidosis occurring in adults with rare mutations of mtDNA. Acute metabolic crisis are often encountered in childhood-onset mitochondrial diseases (MD), whereas adults generally present with progressive neurological or muscle involvement. Investigations included blood analysis, EMG, and muscle biopsy for histoenzymological and respiratory chain analysis. Mitochondrial DNA analysis was performed in muscle, blood, buccal cells, and urine. Patients were one woman and two men, aged 27, 32 and 32years. They presented with slowly progressive muscle weakness and fatigability, compatible with a normal life, several years before the acute metabolic crisis. Two patients experienced prodromal abdominal pain and vomiting; all of them developed acute respiratory failure and collapse needing mechanical ventilation. Concomitant status epilepticus occurred in one patient. Lactic acidosis was present in all cases (20, 24 and 30mM) necessitating extra-renal dialysis. Hepatic cytolysis was constant, contrasting with moderately increased CK levels (3N to 5N). No triggering factor could be identified. All patients fully recovered after prolonged intensive care, but resting lactate levels constantly remained elevated up to 8mM. Muscle biopsy showed numerous ragged-red and COX-negative fibers in two patients, and lipidosis in the third one. Combined deficiency of mtDNA-dependant respiratory complexes was not explained by mtDNA depletion or deletion. Heteroplasmic pathogenic point mutations were detected in tRNA genes: MT-TL1 (m.3280G>A; m.3258C>T) and MT-TK (m8363A>G). Tissue distribution was heterogeneous for the MT-TL1 mutations but homogeneous for the MT-TK mutation. Life-threatening lactic acidosis may be inaugural or a major clinical manifestation in adults with mtDNA mutations. Prolonged intensive care may obtain dramatic and sustained improvement. [Copyright &y& Elsevier]

Published
2013
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32. The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

Author

Alexis Montcuquet, Henrik Kahr Mathiesen, Tomas Kalincik, Marc Girard, Karolina Hankiewicz, Marco Onofrj, Francois Grand Maison, Raed Alroughani, Mathilde Lefort, Olivier Gout, Jeannette Lechner-Scott, Marc Debouverie, Julie Prevost, Eva Havrdova, Olivier Casez, Per Soelberg Sørensen, Pierre Duquette, Jean Pelletier, Claudio Solaro, Alessandra Lugaresi, Francesco Patti, Emmanuelle Leray, Johanna Balslev Andersen, Bassem Yamout, Céline Labeyrie, Karen Schreiber, Eric Thouvenot, Nils Koch-Henriksen, Michael Broksgaard Jensen, Elisabeth Maillart, Chantal Nifle, Stephan Bramow, Pierre Clavelou, Bruno Stankoff, Olivier Heinzlef, Finn Sellebjerg, Abir Wahab, Mark Slee, Gilles Defer, Pierre Labauge, Melinda Magyari, Steve Vucic, Guillermo Izquierdo, Helmut Butzkueven, Peter Vestergaard Rasmussen, Bertrand Bourre, Maria Trojano, Franco Granella, Corinne Pottier, Jette L. Frederiksen, Olga Skibina, Recai Turkoglu, Ivania Patry, Pierre Grammond, Bart Van Wijmeersch, Eric Berger, Aurélie Ruet, Serkan Ozakbas, Jonathan Ciron, Tünde Csépány, Jean Philippe Camdessanche, Sandra Vukusic, Nicolas Maubeuge, David Laplaud, Cavit Boz, Christine Lebrun, Claudia C. Hilt Christensen, Patrizia Sola, Vahid Shaygannejad, Romain Casey, Murat Terzi, Philippe Cabre, Jérôme De Seze, Abdullatif Al-Khedr, Dana Horakova, Pamela A. McCombe, Daniele Spitaleri, Alexandre Prat, Gilles Edan, Hélène Zéphir, Aude Marousset, Sifat Sharmin, Diana Ferraro, Sara Eichau, Rana Karabudak, Thibault Moreau, Sellebjerg, Finn/0000-0002-1333-9623, Lugaresi, Alessandra/0000-0003-2902-5589, frederiksen, jette/0000-0003-1661-7438, Ciron, Jonathan/0000-0002-3386-6308, University of Copenhagen = Københavns Universitet (KU), University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Aarhus University Hospital, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva and Sanofi Genzyme. The study was conducted separately and apart from the guidance of the sponsors. CORe received funding from NHMRC [1140766, 1129789, 1157717] to support studies of comparative effectiveness of MS therapies.OFSEP was supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche,' within the framework of the 'Investments for the Future' program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation.DMSR did not receive any funding to collaborate in this study., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Andersen J.B., Sharmin S., Lefort M., Koch-Henriksen N., Sellebjerg F., Sorensen P.S., Hilt Christensen C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Eichau S., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Shaygannejad V., Prevost J., Skibina O., Solaro C., Karabudak R., Wijmeersch B.V., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., Seze J.D., Maillart E., Zephir H., Labauge P., Defer G., Lebrun C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Marousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Leray E., Laplaud D.A., Butzkueven H., Kalincik T., Vukusic S., Magyari M., University of Copenhagen = Københavns Universitet (UCPH), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], CHU Limoges, Hôpital Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Saint-Denis [Ile-de-France], Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Centre Hospitalier de Versailles André Mignot (CHV)

Subjects
medicine.medical_specialty, Fingolimod, Head-to-head comparison, Multiple sclerosis, Natalizumab, Treatment effectiveness, [SDV]Life Sciences [q-bio], Relapse rate, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, Fingolimod Hydrochloride, Epidemiology, Humans, Medicine, Multiple sclerosi, Registries, 030212 general & internal medicine, business.industry, Hazard ratio, General Medicine, medicine.disease, 3. Good health, First relapse, Treatment Outcome, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Immunosuppressive Agents, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform meth-odologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/ exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab-and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed. BiogenBiogen; NovartisNovartis; MerckMerck & Company; RocheRoche Holding; Teva; Sanofi GenzymeSanofi-AventisGenzyme Corporation; NHMRCNational Health and Medical Research Council of Australia [1140766,1129789, 1157717]; French State; Agence Nationale de la Recherche-French National Research Agency (ANR)European Commission [ANR-10-COHO-002]; Eugene Devic EDMUS Foundation; ARSEP Foundation

Published
2021
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33. Determinants of therapeutic lag in multiple sclerosis

Author

Tomas Kalincik, Marc Girard, Corinne Pottier, Murat Terzi, Jean Pelletier, Oliver Gerlach, Julie Prevost, Dana Horakova, Francois Grand'Maison, Raed Alroughani, Guillermo Izquierdo, Francesco Patti, Federico Frascoli, Maria Trojano, Franco Granella, Pamela A. McCombe, Charles B Malpas, Recai Turkoglu, Aurélie Ruet, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Helmut Butzkueven, Pierre Clavelou, Tamara Castillo Trivino, Marco Onofrj, Jean Philippe Camdessanche, Pierre Labauge, Vincent Van Pesch, Pierre Grammond, Abir Wahab, Roberto Bergamaschi, Aysun Soysal, Diana Ferraro, Bertrand Bourre, Olivier Gout, Jeannette Lechner-Scott, Sara Eichau, Emmanuelle Leray, Alexis Montcuquet, Pierre Duquette, Olivier Casez, Youssef Sidhom, Patrizia Sola, Bart Van Wijmeersch, Izanne Roos, Gilles Edan, Serkan Ozakbas, David Laplaud, Sandra Vukusic, Abdullatif Al Khedr, Céline Labeyrie, Philippe Cabre, Eric Thouvenot, Céline Louapre, Romain Casey, Alessandra Lugaresi, Riadh Gouider, Alasdair Coles, Eric Berger, Ivania Patry, Gerardo Iuliano, Elisabetta Cartechini, Cavit Boz, Karolina Hankiewicz, Eva Havrdova, Eduardo Aguera-Morales, J William L Brown, Jérôme De Seze, Bruno Stankoff, Olivier Heinzlef, Gilles Defer, Alexandre Prat, Chantal Nifle, Maria José Sá, Marc Debouverie, Daniele Spitaleri, Aude Maurousset, Thibault Moreau, Christine Lebrun-Frenay, Hélène Zéphir, University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), Swinburne University of Technology [Melbourne], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Charles University [Prague], Università degli studi di Catania [Catania], Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Università degli Studi di Modena e Reggio Emilia (UNIMORE), University of Queensland [Brisbane], Monash University [Clayton], UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Charles University [Prague] (CU), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Hospital Virgen Macarena, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), CHU Toulouse [Toulouse], INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Fernando Pessoa University, Azienda Ospedaleria Universitaria di Modena, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Karadeniz Technical University (KTU), Università degli Studi di Macerata = University of Macerata (UNIMC), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), University of Newcastle [Australia] (UoN), Zuyderland Hospital [Heerlen, The Netherlands], Ondokuz Mayis University, University of Parma = Università degli studi di Parma [Parme, Italie], Amiri hospital, University of Salerno (UNISA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hasselt University (UHasselt), San Giuseppe Moscati Hospital [Avellino, Italie], Bakirkoy Matern & Childrens State Hosp, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Universidad de Córdoba [Cordoba], Hospital Donostia, CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHI Poissy-Saint-Germain, Université de la Manouba [Tunisie] (UMA), University of Debrecen, Hôpital Charles Nicolle [Rouen], CHU Amiens-Picardie, CHU de la Martinique [Fort de France], CHU Limoges, CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], This study was supported by the EDMUS Foundation and NHMRC [1140766,1129189, 1157717]. IR is supported by a MSIF-ARSEP McDonald fellowship grantand a Melbourne Research Scholarship. The MSBase Foundation is a not-for-profitorganization that receives support from Biogen, Novartis, Merck, Roche, Teva andSanofi Genzyme. The study was conducted separately and apart from the guidanceof the sponsors. The Observatoire Français de la Sclérose en Plaques (OFSEP) issupported by a grant provided by the French State and handled by the 'AgenceNationale de la Recherche,' within the framework of the 'Investments for the Future'program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUSFoundation against multiple sclerosis and by the ARSEP Foundation., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Roos I., Leray E., Frascoli F., Casey R., Brown J.W.L., Horakova D., Havrdova E.K., Debouverie M., Trojano M., Patti F., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grammond P., Ciron J., Ruet A., Ozakbas S., De Seze J., Louapre C., Zephir H., Sa M.J., Sola P., Ferraro D., Labauge P., Defer G., Bergamaschi R., Lebrun-Frenay C., Boz C., Cartechini E., Moreau T., Laplaud D., Lechner-Scott J., Grand'Maison F., Gerlach O., Terzi M., Granella F., Alroughani R., Iuliano G., Van Pesch V., Van Wijmeersch B., Spitaleri D.L.A., Soysal A., Berger E., Prevost J., Aguera-Morales E., McCombe P., Castillo Trivino T., Clavelou P., Pelletier J., Turkoglu R., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Sidhom Y., Gouider R., Csepany T., Bourre B., Al Khedr A., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Coles A., Malpas C.B., Vukusic S., Butzkueven H., Kalincik T., Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli studi di Catania = University of Catania (Unict), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), University of Newcastle [Callaghan, Australia] (UoN), Ondokuz Mayis University (OMU), Università degli studi di Parma = University of Parma (UNIPR), Universidad de Córdoba = University of Córdoba [Córdoba], University of Debrecen Egyetem [Debrecen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Registrie, Male, medicine.medical_specialty, Treatment response, Pediatrics, Neurology, Lag, [SDV]Life Sciences [q-bio], Aucun, multiple sclerosis, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Recurrence, medicine, Humans, Treatment effect, Disabled Persons, Registries, 030304 developmental biology, 0303 health sciences, business.industry, Multiple sclerosis, Delayed onset, medicine.disease, 3. Good health, Clinical neurology, therapeutic lag, multiple sclerosi, Disease Progression, Disabled Person, Observational study, Female, observational study, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract

International audience; Objective: To explore the associations of patient and disease characteristics with the duration of therapeutic lag for relapses and disability progression.Background: Therapeutic lag represents the delay from initiation of therapy to attainment of full treatment effect. Understanding the determinants of therapeutic lag provides valuable information for personalised choice of therapy in multiple sclerosis (MS).Design/Methods: Data from MSBase, a multinational MS registry, and OFSEP, the French national registry, were used. Patients diagnosed with MS, minimum 1-year exposure to MS treatment, minimum 3-year pre-treatment follow up and yearly review were included in the analysis. By studying incidence of relapses and 6-month confirmed disability progression, the duration of therapeutic lag was calculated by identifying the first local minimum of the first derivative after treatment start in subgroups stratified by patient and disease characteristics. Pairwise analyses of univariate predictors were performed. Combinations of determinants that consistently drove differences in therapeutic lag in pair by pair analyses were included in the final model.Results: Baseline EDSS, ARR and sex were associated with duration of therapeutic lag on disability progression in univariate and pairwise bivariable analyses. In the final model, therapeutic lag was 27.8 weeks shorter in females with ARR6 compared to those with EDSS>=6 (26.6, 18.2–34.9 vs 54.3, 47.2–61.5). Baseline EDSS, ARR, sex and MS phenotype were associated with duration of therapeutic lag on relapses in univariate analyses. Pairwise bivariable analyses of the pairs of determinants suggested ependently associated with therapeutic lag. In the final model, therapeutic lag was shortest in those with RRMS and EDSS

Published
2021
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34. Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts

Author

Mark Slee, Guillermo Izquierdo, Per Soelberg Soerensen, Karen Schreiber, Alexandre Prat, Francois Grand'Maison, Maria Trojano, Franco Granella, Pierre Duquette, David Laplaud, Elisabeth Maillart, Henrik Kahr Mathiesen, Bassem Yamout, Cavit Boz, Jean Pelletier, Corinne Pottier, Jette L. Frederiksen, Claudia Christina Pfleger, Tomas Kalincik, Olivier Gout, Daniele Spitaleri, Marc Girard, Marco Onofrj, Jérôme De Seze, Helmut Butzkueven, Emmanuelle Leray, Philippe Cabre, Julie Prevost, Abullatif Al-Khedr, Aude Maurousset, Eric Berger, Sifat Sharmin, Ivania Patry, Pamela A. McCombe, Patrizia Sola, Olga Skibina, Diana Ferraro, Pierre Clavelou, Francesco Patti, Finn Sellebjerg, Niels Koch-Henriksen, Alexis Montcuquet, Recai Turkoglu, Romain Casey, Bart Van Wijmeersch, Hélène Zéphir, Pierre Grammond, Dana Horakova, Davide Maimone, Serkan Ozakbas, Céline Labeyrie, Murat Terzi, Aurélie Ruet, Steve Vucic, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Bruno Stankoff, Mathilde Lefort, Katherine Buzzard, Karolina Hankiewicz, Jean-Philippe Camdessanché, Raed Alroughani, Michael Broksgaard Jensen, Pierre Labauge, Olivier Casez, Peter Vestergaard Rasmussen, Bertrand Bourre, Olivier Heinzlef, Gilles Defer, Gilles Edan, Alessandra Lugaresi, Abir Wahab, Melinda Magyari, Anneke van der Walt, Eva Havrdova, Johanna Balslev Andersen, Chantal Nifle, Stephan Bramow, Marc Debouverie, Thibault Moreau, Sandra Vukusic, Christine Lebrun-Frenay, Jeannette Lechner-Scott, Eric Thouvenot, Sharmin S., Lefort M., Andersen J.B., Leray E., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand'Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Prevost J., Maimone D., Skibina O., Buzzard K., Van der Walt A., Van Wijmeersch B., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., De Seze J., Maillart E., Zephir H., Labauge P., Defer G., Lebrun-Frenay C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Laplaud D., Koch-Henriksen N., Sellebjerg F.T., Soerensen P.S., Pfleger C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Magyari M., Vukusic S., Butzkueven H., Kalincik T., University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH), École des Hautes Études en Santé Publique [EHESP] (EHESP), Charles University [Prague] (CU), Amiri hospital, Hospital Virgen Macarena, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), University of Catania [Italy], G.F. Ingrassia Hospital, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Neurological Science of Bologna (IRCCS), Ondokuz Mayis University (OMU), American University of Beirut Faculty of Medicine and Medical Center (AUB), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Karadeniz Technical University (KTU), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), University of Queensland [Brisbane], Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Flinders University [Adelaide, Australia], University of Newcastle [Callaghan, Australia] (UoN), Azienda Ospedaleria Universitaria di Modena, Università degli studi di Parma = University of Parma (UNIPR), University Hospital Parma, Monash University [Melbourne], The Alfred Hospital, Hasselt University (UHasselt), University of Debrecen Egyetem [Debrecen], San Giuseppe Moscati Hospital [Avellino, Italie], Westmead Hospital [Sydney], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Eugène Devic EDMUS, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Pasteur [Nice] (CHU), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHI Poissy-Saint-Germain, Service de neurologie [Amiens], CHU Amiens-Picardie, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], Service de Neurologie [CHU Limoges], CHU Limoges, CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital Sud Francilien Corbeil Essonne, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Versailles André Mignot (CHV), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Aarhus University Hospital, Aalborg University [Denmark] (AAU), University Hospital of Northern Sealand, Rigshospitalet [Copenhagen], Copenhagen University Hospital, The Royal Melbourne Hospital, 1140766, National Health and Medical Research Council, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (KU), Università degli Studi di Bologna, University of Bari Aldo Moro (UNIBA), University of Newcastle [Australia] (UoN), University of Parma = Università degli studi di Parma [Parme, Italie], University of Debrecen, Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Ondokuz Mayis University, Centre de recherche en neurosciences de Lyon (CRNL), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Internationality, Subgroup analysis, Rate ratio, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, 030225 pediatrics, Internal medicine, Secondary Prevention, Medicine, Humans, Immunologic Factors, Pharmacology (medical), Longitudinal Studies, Registries, 10. No inequality, Expanded Disability Status Scale, business.industry, Proportional hazards model, Fingolimod Hydrochloride, Multiple sclerosis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, medicine.disease, Fingolimod, 3. Good health, multiple sclerosis, sex, age, natalizumab, fingolimod, big data, Psychiatry and Mental health, Cohort, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug, Follow-Up Studies
Abstract

Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined. Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest. Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients’ sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed withweighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score. Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15–41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65–0.88); in those aged ≤38 years (0.64; 0.54–0.76); in those withdisease duration ≤7 years (0.63; 0.53–0.76); in those with EDSS score 38 years (1.34; 1.04–1.73); those with disease duration >7 years (1.33; 1.01–1.74); those with EDSS score

Published
2021
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35. Synthetic and biodegradable prostheses in pelvic floor surgery

Author

Deprest, J., Claerhout, F., Zheng, F., Konstantinovic, M., Spelzini, F., Guelinckx, I., Pottier, C., Verbeken, E., and De Ridder, D.

Subjects
*PELVIC diseases, *ARTIFICIAL joints, *THERAPEUTICS, *SURGERY
Abstract

Abstract: Pelvic organ prolapse is an increasingly frequent problem and surgical repair remains the mainstay of therapy. Failure rates are as high as 30%, probably because the connective tissue used for repair is by definition qualitatively insufficient. There is therefore a lot of interest for augmentation of fascial repairs with implants. Experimental studies play an important role in the evaluation of such materials, documenting in vivo tensile strength, the host response to these foreign materials, particularly over longer periods. Non-reabsorbable synthetic implants lead to a permanent repair but the host usually develops a chronic inflammatory reaction which can be associated with bothersome side effects. Biological materials on the other hand have been much less studied and little is known about their long-term tissue response. They may, however, have their role as they may lead to less local side effects which may be mastered conservatively. The ultimate test for any material is obviously the clinical trial, defining its role in practice. [Copyright &y& Elsevier]

Published
2005
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36. The contribution of 14C AMS dating to the Greater Angkor archaeological project

Author

Zoppi, U., Barbetti, M., Fletcher, R., Hua, Q., Chhem, R.K., Pottier, C., and Watanasak, M.

Subjects
*ACCELERATOR mass spectrometry, *ARCHAEOLOGY
Abstract

For well over five centuries, the Khmer kingdom ruled over a vast territory, including most of what is now known as Cambodia, Thailand, Vietnam and Laos. Between the 9th and 14th century AD, the Khmer Kings developed the Angkor area into a remarkable administrative and religious centre for their society. According to new estimates by the Greater Angkor Project, the entire urban complex of the capital city covered about 1000 square km making it probably the largest archaeological site in the world. Great stone temples and some other monumental structures and earthworks are the only visible remains of this fascinating civilisation. Thankfully, there is a substantial on-going multinational effort to preserve and restore what is left and in 1992 UNESCO (United Nations Educational Scientific and Cultural Organisation) declared Angkor a World Heritage Site. This paper presents two particular aspects of the Greater Angkor Project where radiocarbon dating by AMS specifically added to our knowledge of the history of this ancient capital city. [Copyright &y& Elsevier]

Published
2004
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37. Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis

Author

Patrick Vermersch, Ivania Patry, Nicolas Maubeuge, Catherine Lubetzki, Ofsep Study Groups, David-Axel Laplaud, Bruno Stankoff, Bruno Brochet, Eric Thouvenot, Céline Labeyrie, Jean-Philippe Camdessanché, Olivier Gout, Laure Michel, Chantal Nifle, Abdullatif Al Khedr, Emmanuelle Leray, Gilles Edan, Marc Debouverie, Laetitia Barbin, David Brassat, Yohann Foucher, Thibault Moreau, Romain Casey, Jean Pelletier, Christine Lebrun-Frenay, Sandra Vukusic, Laurent Magy, Olivier Heinzlef, Philippe Cabre, Caroline Papeix, Ayman Tourbah, Gilles Defer, Abir Wahab, Pierre Clavelou, Eric Berger, Jérôme De Seze, A.-M. Guennoc, Fabien Rollot, Olivier Casez, Sandrine Wiertlewski, Thomas Debroucker, Pierre Labauge, Bertrand Bourre, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service de Neurologie [Lyon], CHU Lyon, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de neurologie [Rennes], Université de Rennes (UR), Department of Neurology, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de neurologie [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Public Health Agency of Canada, CHI Poissy-Saint-Germain, Service de Neurologie [CHU de Poissy], CHU De Poissy, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherches Critiques sur le Droit (CERCRID), Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de Neurologie [CHU Limoges], CHU Limoges, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), École des Hautes Études en Santé Publique [EHESP] (EHESP), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Supported by Fondation ARSEP, CHU Nantes (Appel d’Offre Interne), and Association ANTARES. The French Observatoire of Multiple Sclerosis is supported by a grant provided by the French State and handled by the Agence Nationale de la Recherche, within the framework of the Investments for the Future program, under the reference ANR-10-COHO-002. The study was supported by West Neurosciences Network and Société Francophone de Scl´erose en Plaques, Fondation ARSEP, and by Appel d’Offre Interne du CHU de Nantes., SFSEP and OFSEP groups : Fontaine B, Marignier R, Durand-Dubief F, Mathey G, Le Page E, Peaureaux-Averseng D, Ouallet JC, Ruet A, Collongues N, Hautecoeur P, Zephir H, Maillard E, Cohen M, Derache N, Branger P, Ayrignac X, Carra-Dalliere C, Fromont A, Chamard-Witkowski L, Taithe F, Moisset X, Audoin B, Rico-Lamy A, Castelnovo G, Giannesini C, Fagniez O, Bensa C, Gueguen A, Kasonde IT, De Vilmarest A, Montcuquet A, Vaillants M, Beltran S, Creange A, Ayache S, Abdellaoui M, Pottier C, Slesari I, Deburghraeve V, Neau JP, Servan J, Pico F, Henry C, Hankiewicz K., Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de neurologie, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Saint-Etienne, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2), Fondation Ophtalmologique Rothschild, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université de Montpellier (UM)-Université Montpellier 1 (UM1), Le Bihan, Sylvie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)

Subjects
Adult, Male, medicine.medical_specialty, Toluidines, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hydroxybutyrates, Effectiveness, Dimethyl fumarate, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Internal medicine, Teriflunomide, Nitriles, medicine, Humans, 030212 general & internal medicine, 10. No inequality, Adverse effect, ComputingMilieux_MISCELLANEOUS, Intention-to-treat analysis, Expanded Disability Status Scale, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Fingolimod Hydrochloride, Odds ratio, Middle Aged, Discontinuation, Treatment Outcome, chemistry, Crotonates, Propensity score matching, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ObjectiveIn this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques.MethodsA total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated.ResultsThe confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001).ConclusionsAfter 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment.

Published
2019
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38. Haploinsufficiency of lysosomal enzyme genes in Alzheimer's disease.

Author

Benitez BA, Wallace CE, Patel M, Nykanen NP, Yuede CM, Eaton SL, Pottier C, Cetin A, Johnson M, Bevan MT, Gardiner WD, Edwards HM, Doherty BM, Harrigan RT, Kurian D, Wishart TM, Smith C, Cirrito JR, and Sands MS

Abstract

There is growing evidence suggesting that the lysosome or lysosome dysfunction is associated with Alzheimer's disease (AD). Pathway analysis of post mortem brain-derived proteomic data from AD patients shows that the lysosomal system is perturbed relative to similarly aged unaffected controls. However, it is unclear if these changes contributed to the pathogenesis or are a response to the disease. Consistent with the hypothesis that lysosome dysfunction contributes to AD pathogenesis, whole genome sequencing data indicate that heterozygous pathogenic mutations and predicted protein-damaging variants in multiple lysosomal enzyme genes are enriched in AD patients compared to matched controls. Heterozygous loss-of-function mutations in the palmitoyl protein thioesterase-1 ( PPT1 ), α-L-iduronidase ( IDUA ), β-glucuronidase ( GUSB ), N-acetylglucosaminidase ( NAGLU ), and galactocerebrosidase ( GALC ) genes have a gene-dosage effect on Aβ 40 levels in brain interstitial fluid in C57BL/6 mice and significantly increase Aβ plaque formation in the 5xFAD mouse model of AD, thus providing in vivo validation of the human genetic data. A more detailed analysis of PPT1 heterozygosity in 18-month-old mice revealed changes in α-, β-, and γ-secretases that favor an amyloidogenic pathway. Proteomic changes in brain tissue from aged PPT1 heterozygous sheep are consistent with both the mouse data and the potential activation of AD pathways. Finally, CNS-directed, AAV-mediated gene therapy significantly decreased Aβ plaques, increased life span, and improved behavioral performance in 5xFAD/PPT1+/- mice. Collectively, these data strongly suggest that heterozygosity of multiple lysosomal enzyme genes represent risk factors for AD and may identify precise therapeutic targets for a subset of genetically-defined AD patients.

Published
2024
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39. Acute Clinical Events Identified as Relapses With Stable Magnetic Resonance Imaging in Multiple Sclerosis.

Author

Gavoille A, Rollot F, Casey R, Kerbrat A, Le Page E, Bigaut K, Mathey G, Michel L, Ciron J, Ruet A, Maillart E, Labauge P, Zephir H, Papeix C, Defer G, Lebrun-Frenay C, Moreau T, Berger E, Stankoff B, Clavelou P, Thouvenot E, Heinzlef O, Pelletier J, Al-Khedr A, Casez O, Bourre B, Cabre P, Wahab A, Magy L, Camdessanché JP, Doghri I, Moulin S, Ben-Nasr H, Labeyrie C, Hankiewicz K, Neau JP, Pottier C, Nifle C, Manchon E, Lapergue B, Wiertlewski S, De Sèze J, Vukusic S, and Laplaud DA

Subjects
Humans, Female, Male, Adult, Middle Aged, Cohort Studies, Spinal Cord diagnostic imaging, Spinal Cord pathology, Brain diagnostic imaging, Disease Progression, Gadolinium, Registries, Magnetic Resonance Imaging methods, Recurrence, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Importance: Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development., Objective: To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI)., Design, Setting, and Participants: This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection., Exposures: Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise., Main Outcomes and Measures: Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated., Results: Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs., Conclusions and Relevance: The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Published
2024
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40. Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing.

Author

Pottier C, Küçükali F, Baker M, Batzler A, Jenkins GD, van Blitterswijk M, Vicente CT, De Coster W, Wynants S, Van de Walle P, Ross OA, Murray ME, Faura J, Haggarty SJ, van Rooij JG, Mol MO, Hsiung GR, Graff C, Öijerstedt L, Neumann M, Asmann Y, McDonnell SK, Baheti S, Josephs KA, Whitwell JL, Bieniek KF, Forsberg L, Heuer H, Lago AL, Geier EG, Yokoyama JS, Oddi AP, Flanagan M, Mao Q, Hodges JR, Kwok JB, Domoto-Reilly K, Synofzik M, Wilke C, Onyike C, Dickerson BC, Evers BM, Dugger BN, Munoz DG, Keith J, Zinman L, Rogaeva E, Suh E, Gefen T, Geula C, Weintraub S, Diehl-Schmid J, Farlow MR, Edbauer D, Woodruff BK, Caselli RJ, Donker Kaat LL, Huey ED, Reiman EM, Mead S, King A, Roeber S, Nana AL, Ertekin-Taner N, Knopman DS, Petersen RC, Petrucelli L, Uitti RJ, Wszolek ZK, Ramos EM, Grinberg LT, Gorno Tempini ML, Rosen HJ, Spina S, Piguet O, Grossman M, Trojanowski JQ, Keene DC, Lee-Way J, Prudlo J, Geschwind DH, Rissman RA, Cruchaga C, Ghetti B, Halliday GM, Beach TG, Serrano GE, Arzberger T, Herms J, Boxer AL, Honig LS, Vonsattel JP, Lopez OL, Kofler J, White CL, Gearing M, Glass J, Rohrer JD, Irwin DJ, Lee EB, Van Deerlin V, Castellani R, Mesulam MM, Tartaglia MC, Finger EC, Troakes C, Al-Sarraj S, Miller BL, Seelaar H, Graff-Radford NR, Boeve BF, Mackenzie IR, van Swieten JC, Seeley WW, Sleegers K, Dickson DW, Biernacka JM, and Rademakers R

Abstract

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor. In subgroup analyses, we further identify for the first time genome-wide significant loci specific to each of the three main FTLD-TDP pathological subtypes (A, B and C), as well as enrichment of risk loci in distinct tissues, brain regions, and neuronal subtypes, suggesting distinct disease aetiologies in each of the subtypes. Rare variant analysis confirmed TBK1 and identified VIPR1 , RBPJL , and L3MBTL1 as novel subtype specific FTLD-TDP risk genes, further highlighting the role of innate and adaptive immunity and notch signalling pathway in FTLD-TDP, with potential diagnostic and novel therapeutic implications.

Published
2024
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41. Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease.

Author

Kouri N, Frankenhauser I, Peng Z, Labuzan SA, Boon BDC, Moloney CM, Pottier C, Wickland DP, Caetano-Anolles K, Corriveau-Lecavalier N, Tranovich JF, Wood AC, Hinkle KM, Lincoln SJ, Spychalla AJ, Senjem ML, Przybelski SA, Engelberg-Cook E, Schwarz CG, Kwan RS, Lesser ER, Crook JE, Carter RE, Ross OA, Lachner C, Ertekin-Taner N, Ferman TJ, Fields JA, Machulda MM, Ramanan VK, Nguyen AT, Reichard RR, Jones DT, Graff-Radford J, Boeve BF, Knopman DS, Petersen RC, Jack CR Jr, Kantarci K, Day GS, Duara R, Graff-Radford NR, Dickson DW, Lowe VJ, Vemuri P, and Murray ME

Subjects
Humans, Male, Female, Aged, Aged, 80 and over, Cross-Sectional Studies, Retrospective Studies, Neurofibrillary Tangles pathology, tau Proteins metabolism, Middle Aged, Neuroimaging, Cohort Studies, Brain diagnostic imaging, Brain pathology, Brain metabolism, Autopsy, Alzheimer Disease diagnostic imaging, Alzheimer Disease pathology, Alzheimer Disease metabolism, Neuroglia pathology, Neuroglia metabolism, Magnetic Resonance Imaging, Positron-Emission Tomography
Abstract

Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement., Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy., Design, Setting, and Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses., Main Outcomes and Measures: Clinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET)., Results: Of the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02)., Conclusions and Relevance: Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.

Published
2024
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42. High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS.

Author

Jouvenot G, Courbon G, Lefort M, Rollot F, Casey R, Le Page E, Michel L, Edan G, de Seze J, Kremer L, Bigaut K, Vukusic S, Mathey G, Ciron J, Ruet A, Maillart E, Labauge P, Zephir H, Papeix C, Defer G, Lebrun-Frenay C, Moreau T, Laplaud DA, Berger E, Stankoff B, Clavelou P, Thouvenot E, Heinzlef O, Pelletier J, Al-Khedr A, Casez O, Bourre B, Cabre P, Wahab A, Magy L, Camdessanché JP, Doghri I, Moulin S, Ben-Nasr H, Labeyrie C, Hankiewicz K, Neau JP, Pottier C, Nifle C, Collongues N, and Kerbrat A

Subjects
Humans, Female, Male, Middle Aged, Cohort Studies, Fingolimod Hydrochloride therapeutic use, Immunologic Factors therapeutic use, Immunologic Factors administration & dosage, Registries, Aged, Withholding Treatment, Immunosuppressive Agents therapeutic use, Multiple Sclerosis drug therapy, Natalizumab therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Importance: A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity., Objective: To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET., Design, Setting, and Participants: This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022., Exposures: Natalizumab, fingolimod, rituximab, and ocrelizumab., Main Outcomes and Measures: Time to first relapse., Results: Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy., Conclusion and Relevance: As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.

Published
2024
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43. Knowledge of community pharmacists on infantile haemangioma: Gaps and lack confidence to deliver propranolol still need to be filled.

Author

Pottier C, Guichard E, Thomann C, Denevault-Sabourin C, Maruani A, and Leducq S

Subjects
Humans, Female, Adult, Male, Pharmacists, Surveys and Questionnaires, Health Personnel, Propranolol therapeutic use, Hemangioma drug therapy
Abstract

Aim: To evaluate the knowledge, practices and self-confidence of community pharmacists, pharmacy technicians and pharmacy students about infantile haemangioma (IH) and propranolol treatment., Methods: A national survey was conducted in France from May 2022 to October 2022. A 42-item online questionnaire was used to assess pharmacists' knowledge of the epidemiology, clinical features and management of IH and propranolol treatment., Results: The survey included 255 participants. The mean age was 34.9 years (±9.0); 225 (88%) were women. In all, 193 (76%) practised in urban pharmacies. Altogether, 83 participants (33%) had delivered oral propranolol solution for IH in the last 6 months. Participants' median score for self-confidence regarding propranolol dispensing was five (interquartile range, 2.5-6) on a scale of 1 to 10. Overall, 96 (38%) had more than 50% correct answers on the questionnaire. Multinomial regression models showed high scores on the questionnaire associated with high self-confidence when delivering oral propranolol solution, low number of years since graduation and having already delivered propranolol treatment., Conclusion: This study highlights a lack of knowledge of IH and modalities of propranolol treatment by community pharmacists and slight self-confidence when delivering propranolol. Greater cooperation between healthcare professionals could improve the proper use of medicine., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Published
2024
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44. Abundant transcriptomic alterations in the human cerebellum of patients with a C9orf72 repeat expansion.

Author

Udine E, DeJesus-Hernandez M, Tian S, das Neves SP, Crook R, Finch NA, Baker MC, Pottier C, Graff-Radford NR, Boeve BF, Petersen RC, Knopman DS, Josephs KA, Oskarsson B, Da Mesquita S, Petrucelli L, Gendron TF, Dickson DW, Rademakers R, and van Blitterswijk M

Subjects
Humans, DNA Repeat Expansion genetics, Gene Expression Profiling, Transcriptome, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis pathology, C9orf72 Protein genetics, C9orf72 Protein metabolism, Cerebellum pathology, Frontotemporal Lobar Degeneration genetics, Frontotemporal Lobar Degeneration metabolism, Frontotemporal Lobar Degeneration pathology
Abstract

The most prominent genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is a repeat expansion in the gene C9orf72. Importantly, the transcriptomic consequences of the C9orf72 repeat expansion remain largely unclear. Here, we used short-read RNA sequencing (RNAseq) to profile the cerebellar transcriptome, detecting alterations in patients with a C9orf72 repeat expansion. We focused on the cerebellum, since key C9orf72-related pathologies are abundant in this neuroanatomical region, yet TDP-43 pathology and neuronal loss are minimal. Consistent with previous work, we showed a reduction in the expression of the C9orf72 gene and an elevation in homeobox genes, when comparing patients with the expansion to both patients without the C9orf72 repeat expansion and control subjects. Interestingly, we identified more than 1000 alternative splicing events, including 4 in genes previously associated with ALS and/or FTLD. We also found an increase of cryptic splicing in C9orf72 patients compared to patients without the expansion and controls. Furthermore, we demonstrated that the expression level of select RNA-binding proteins is associated with cryptic splice junction inclusion. Overall, this study explores the presence of widespread transcriptomic changes in the cerebellum, a region not confounded by severe neurodegeneration, in post-mortem tissue from C9orf72 patients., (© 2024. The Author(s).)

Published
2024
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45. Photometric stereo data for the validation of a structural health monitoring test rig.

Author

Blair J, Stephen B, Brown B, McArthur S, Gorman D, Forbes A, Pottier C, McAlorum J, Dow H, and Perry M

Abstract

Photometric stereo uses images of objects illuminated from various directions to calculate surface normals which can be used to generate 3D meshes of the object. Such meshes can be used by engineers to estimate damage of a concrete surface, or track damage progression over time to inform maintenance decisions. This dataset [1] was collected to quantify the uncertainty in a photometric stereo test rig through both the comparison with a well characterised method (coordinate measurement machine) and experiment virtualisation. Data was collected for 9 real objects using both the test rig and the coordinate measurement machine. These objects range from clay statues to damaged concrete slabs. Furthermore, synthetic data for 12 objects was created via virtual renders generated using Blender (3D software) [2]. The two methods of data generation allowed the decoupling of the physical rig (used to light and photograph objects) and the photometric stereo algorithm (used to convert images and lighting information into 3D meshes). This data can allow users to: test their own photometric stereo algorithms, with specialised data created for structural health monitoring applications; provide an industrially relevant case study to develop and test uncertainty quantification methods on test rigs for structural health monitoring of concrete; or develop data processing methodologies for the alignment of scaled, translated, and rotated data., (© 2024 The Author(s).)

Published
2024
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46. Impact of adjuvant radiation therapy on survival and recurrence in patients with stage I-III Merkel cell carcinoma: A retrospective study of 312 patients.

Author

Pottier C, Marchand A, Kervarrec T, Le Corre Y, Nardin C, Aubin F, Wierzbicka-Hainaut E, Cassecuel J, Dreno B, Bens G, Beneton N, Legoupil D, Dinulescu M, Saiag P, Fily-Blom A, and Samimi M

Subjects
Humans, Retrospective Studies, Radiotherapy, Adjuvant, Prognosis, Neoplasm Recurrence, Local epidemiology, Neoplasm Staging, Carcinoma, Merkel Cell, Skin Neoplasms pathology
Abstract

Competing Interests: Conflicts of interest None disclosed.

Published
2023
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47. Four uncommon clinical fungi, Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii and Wickerhamomyces anomalus, isolated in superficial samples from Côte d'Ivoire.

Author

Ira AVB, Krasteva D, Kouadjo F, Roger F, Bellet V, Koffi D, Pottier C, Toure OA, Drakulovski P, Djaman AJ, Ranque S, and Bertout S

Subjects
Female, Humans, Cote d'Ivoire epidemiology, Yeasts, Fungi, Mycoses epidemiology
Abstract

Aims: The rare yeast species Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus are increasingly implicated in severe mycoses in immunocompromised patients. This study aimed to assess the prevalence of uncommon yeast species in Côte d'Ivoire., Methods: The yeast isolates from superficial samples, mainly vaginal swabs, were collected at the Pasteur Institute of Abidjan in a study on the molecular epidemiology of clinical yeast species. Identification relied on MALDI-TOF MS and ITS sequence analysis. Antifungal susceptibility testing was performed using the CLSI method., Results: Of the 315 strains analysed from 227 outpatients, 14 belonged to 4 uncommon species: Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus. None exhibited elevated fluconazole, amphotericin B, caspofungin, ketoconazole, or flucytosin MIC., Conclusions: The presence of these rare yeasts represents a risk in immunocompromised people. Their adequate and timely identification is a priority. Overall, enhancing the mycoses diagnostic capacities in Côte d'Ivoire, and more generally in African clinical laboratories with limited resources is a critical aim., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Published
2023
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48. The SERPINA5 coding variant E228Q does not contribute to clinicopathologic characteristics in Alzheimer's disease: A cross-sectional study.

Author

Matchett BJ, Lincoln SJ, Baker M, Tamvaka N, Labuzan SA, Hicks Sirmans TN, Moloney CM, Helminger J, Hinkle KM, Cabrera-Rodriguez J, Wickland DP, Johnson PW, Heckman MG, Reddy JS, Younkin SG, Carrasquillo MM, Duara R, Graff-Radford NR, Pottier C, Ertekin-Taner N, Ross OA, Rademakers R, Dickson DW, and Murray ME

Subjects
Humans, Cross-Sectional Studies, Neurofibrillary Tangles metabolism, Neurofibrillary Tangles pathology, Brain pathology, Hippocampus metabolism, tau Proteins genetics, tau Proteins metabolism, Protein C Inhibitor metabolism, Alzheimer Disease metabolism
Abstract

We previously demonstrated that increased expression of the SERPINA5 gene is associated with hippocampal vulnerability in Alzheimer's disease (AD) brains. SERPINA5 was further demonstrated to be a novel tau-binding partner that colocalizes within neurofibrillary tangles. Our goal was to determine whether genetic variants in the SERPINA5 gene contributed to clinicopathologic phenotypes in AD. To screen for SERPINA5 variants, we sequenced 103 autopsy-confirmed young-onset AD cases with a positive family history of cognitive decline. To further assess the frequency of a rare missense variant, SERPINA5 p.E228Q, we screened an additional 1114 neuropathologically diagnosed AD cases. To provide neuropathologic context in AD, we immunohistochemically evaluated SERPINA5 and tau in a SERPINA5 p.E228Q variant carrier and a matched noncarrier. In the initial SERPINA5 screen, we observed 1 individual with a rare missense variant (rs140138746) that resulted in an amino acid change (p.E228Q). In our AD validation cohort, we identified an additional 5 carriers of this variant, resulting in an allelic frequency of 0.0021. There was no significant difference between SERPINA5 p.E228Q carriers and noncarriers in terms of demographic or clinicopathologic characteristics. Although not significant, on average SERPINA5 p.E228Q carriers were 5 years younger at age of disease onset than noncarriers (median: 66 [60-73] vs 71 [63-77] years, P = .351). In addition, SERPINA5 p.E228Q carriers exhibited a longer disease duration than noncarriers that approached significance (median: 12 [10-15]) vs 9 [6-12] years, P = .079). More severe neuronal loss was observed in the locus coeruleus, hippocampus, and amygdala of the SERPINA5 p.E228Q carrier compared to noncarrier, although no significant difference in SERPINA5-immunopositive lesions was observed. Throughout the AD brain in either carrier or noncarrier, areas with early pretangle pathology or burnt-out ghost tangle accumulation did not reveal SERPINA5-immunopositive neurons. Mature tangles and newly formed ghost tangles appeared to correspond well with SERPINA5-immunopositive tangle-bearing neurons. SERPINA5 gene expression was previously associated with disease phenotype; however, our findings suggest that SERPINA5 genetic variants may not be a contributing factor to clinicopathologic differences in AD. SERPINA5-immunopositive neurons appear to undergo a pathologic process that corresponded with specific levels of tangle maturity., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Published
2023
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49. Exposure of Cryptococcus neoformans to Seven Commonly Used Agricultural Azole Fungicides Induces Resistance to Fluconazole as Well as Cross-Resistance to Voriconazole, Posaconazole, Itraconazole and Isavuconazole.

Author

Drakulovski P, Krasteva D, Bellet V, Randazzo S, Roger F, Pottier C, and Bertout S

Abstract

Background: Cross-resistance to medical azoles by exposure to azole pesticides is well documented for Aspergillus family fungi but is poorly evaluated for other environmental pathogen fungi, particularly for yeasts belonging to the Cryptococcus neoformans / Cryptococcus gattii species complexes., Methods: One thousand C. neoformans yeast were exposed to various concentrations of seven different commonly used azole pesticides. Clones surviving exposure were picked randomly, and their minimal inhibitory concentrations (MICs) of fluconazole, voriconazole, posaconazole, itraconazole and isavuconazole were assessed., Results: Depending on the pesticide used for exposure, up to 13.3% of selected Cryptococcus colonies showed a phenotype of resistance to fluconazole, and among them, several showed cross-resistance to another or several other medical azoles. Molecular mechanisms involved in the resistance setups seem to be dependent on ERG11 and AFR1 gene overexpression., Conclusion: Exposure to any of the seven azole pesticides tested is capable of increasing the MIC of fluconazole in C. neoformans , including up to the level of the fluconazole-resistant phenotype, as well as generating cross-resistance to other medical azoles in some cases.

Published
2023
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50. Investigating the Long-term Effect of Pregnancy on the Course of Multiple Sclerosis Using Causal Inference.

Author

Gavoille A, Rollot F, Casey R, Debouverie M, Le Page E, Ciron J, De Seze J, Ruet A, Maillart E, Labauge P, Zephir H, Papeix C, Defer G, Lebrun-Frenay C, Moreau T, Laplaud DA, Berger E, Stankoff B, Clavelou P, Thouvenot E, Heinzlef O, Pelletier J, Al Khedr A, Casez O, Bourre B, Cabre P, Wahab A, Magy L, Camdessanche JP, Maurousset A, Moulin S, Ben NH, Boulos DD, Hankiewicz K, Neau JP, Pottier C, Nifle C, Rabilloud M, Subtil F, and Vukusic S

Subjects
Pregnancy, Humans, Female, Cohort Studies, Probability, Recurrence, Disease Progression, Multiple Sclerosis epidemiology, Disabled Persons, Multiple Sclerosis, Relapsing-Remitting
Abstract

Background and Objectives: The question of the long-term safety of pregnancy is a major concern in patients with multiple sclerosis (MS), but its study is biased by reverse causation (women with higher disability are less likely to experience pregnancy). Using a causal inference approach, we aimed to estimate the unbiased long-term effects of pregnancy on disability and relapse risk in patients with MS and secondarily the short-term effects (during the perpartum and postpartum years) and delayed effects (occurring beyond 1 year after delivery)., Methods: We conducted an observational cohort study with data from patients with MS followed in the Observatoire Français de la Sclérose en Plaques registry between 1990 and 2020. We included female patients with MS aged 18-45 years at MS onset, clinically followed up for more than 2 years, and with ≥3 Expanded Disease Status Scale (EDSS) measurements. Outcomes were the mean EDSS score at the end of follow-up and the annual probability of relapse during follow-up. Counterfactual outcomes were predicted using the longitudinal targeted maximum likelihood estimator in the entire study population. The patients exposed to at least 1 pregnancy during their follow-up were compared with the counterfactual situation in which, contrary to what was observed, they would not have been exposed to any pregnancy. Short-term and delayed effects were analyzed from the first pregnancy of early-exposed patients (who experienced it during their first 3 years of follow-up)., Results: We included 9,100 patients, with a median follow-up duration of 7.8 years, of whom 2,125 (23.4%) patients were exposed to at least 1 pregnancy. Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference [95% CI] = 0.00 [-0.16 to 0.15]) or on the annual probability of relapse (causal risk ratio [95% CI] = 0.95 [0.93-1.38]). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate., Discussion: Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias., (© 2022 American Academy of Neurology.)

Published
2023
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