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1. A Review of High-Intensity Focused Ultrasound

Author

Ben Turner and David Cranston

Subjects
high-intensity focused ultrasound, minimally invasive surgery, abdominal malignancy, targeted drug delivery, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

For 80 years, high-intensity focused ultrasound (HIFU) has been the subject of interest in medical research. It is a non-invasive procedure that causes the death of cells in a very select area through one of two mechanisms, either heat or cavitation. While diagnostic ultrasound is well known in the medical profession and ultrasound is also used in physiotherapy, high-intensity focused ultrasound is less known but is becoming increasingly important as a non-invasive tool that can be used in many ways, including in the treatment of several cancers as well as benign uterine fibroids. Other interesting developments are underway, including its use in the treatment through an intact skull of essential tremors and the tremor associated with Parkinson’s disease, and in a modified form, it is used to target drug delivery to the brain due to its potential opening of the blood–brain barrier. The depth of penetration of HIFU is variable depending on the type of transducer used and the distance from it. Clinical trials of abdominal malignancies and benign uterine fibroids are reviewed in this article along with potential side effects of the procedure. Over the past two decades, the technology has improved considerably, and the clinical indications have broadened. The current limitations of the technology are also discussed, along with the potential advances in the field that may be made over the next decade.

Published
2024
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2. Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial

Author

Gavin Giovannoni, Stephen J Walters, David Paling, Olga Ciccarelli, Cindy Cooper, Eli Silber, Martin Duddy, Hannah Hunter, David Hunt, Basil Sharrack, Paul Gallagher, Ian Galea, Richard Nicholas, Annalena Venneri, Neil Robertson, Carolyn Young, Jeremy Hobart, David Rog, Ben Turner, Muhammad Saif, Azza Ismail, Gavin Brittain, John A Snowden, Diana Papaioannou, Alasdair J Coles, Gordon Mazibrada, Neil Scolding, Maruthi Vinjam, Matthew Bursnall, Claire Rice, Ian Pomeroy, Majid Kazmi, Esmaeil Nikfekr, Kim Orchard, Thushan de Silva, Jennifer Petrie, Elisa Roldan, Caroline Besley, Kate E M Duffy, Rachel Glover, Katie Hullock, Colette Beecher, Ian Gabriel, Charalampia Kyriakou, Andy Peniket, Paolo A Muraro, Amy Publicover, Andy Clark, Charles Crawley, Eleni Tholouli, Fran Kinsella, Gabriele De Luca, Jeff Davies, Jenny Byrne, Keith Campbell, Leonora Finisku, Simon Bulley, and Vic Campbell

Subjects
Medicine
Abstract

Introduction Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, ‘Multiple Sclerosis International Stem Cell Transplant, MIST’, showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS.Methods and analysis StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve ‘no evidence of disease activity’ during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs.Ethics and dissemination The study was approved by the Yorkshire and Humber—Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences.Trial registration number ISRCTN88667898.

Published
2024
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3. Higher Hepatitis C Cure Rates in a Patient-Centered Medical Home Compared to Specialist Care

Author

Jonathan Hughes, Nicholas Hodge, Amber Shadoan, Courtney Ellis, Ben Turner, and Craig Glass

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

Purpose: The new era of direct-acting antivirals (DAAs) against the hepatitis C virus (HCV) has led many primary care clinicians to begin treating HCV. Nevertheless, many patients are referred to specialists due to comorbidities, care complexities, and knowledge gaps of the primary care provider. We compared clinical outcomes for patients treated within a Family Medicine Residency Program (FMRP) affiliated patient-centered medical home (PCMH) with those referred to a specialist. Methods: Following didactic education and development of practice resources we conducted a single-center quasi-experimental study of adults with HCV referred for treatment either internally or externally to a specialist between January 2019 and December 2020. The primary outcome was the number of patients with a sustained virologic response at 12 weeks after treatment (SVR12), utilizing an intention-to-treat analysis. Results: During the study period 107 patients were assessed by the PCMH, of whom 24 were deemed not a good candidate for treatment. Of the 83 patients referred for treatment, 36 patients were referred externally and 47 were treated internally. While the rate of SVR12 was 100% for both groups when analyzed per protocol (ie, only patients who completed treatment and attended all follow-ups), the rate of SVR12 was 31% for patients referred externally and 62% for patients treated internally when analyzed by intention to treat (relative risk [RR] 2.02, 95% CI 1.18-3.47, P = .01). This difference was entirely attributable to differences in lost to follow-up rates. Conclusions: Following education and creation of practice resources, achievement of SVR12 among patients with HCV treated by an internal interdisciplinary family medicine team was superior to those who were externally referred. This was primarily attributable to differences in follow-up rates.

Published
2023
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4. Wayfinding Serendipity: The BKFNDr Mobile App

Author

Valeda Dent, Kiichi Takeuchi, Ben Turner, Heather Ball, Caroline Fuchs, Ann Jusino, and Shilpa Karnik

Subjects
Bibliography. Library science. Information resources
Abstract

Librarians and staff at St. John’s University Libraries created BKFNDr, a beacon-enabled mobile wayfinding app designed to help students locate print materials on the shelves at two campus libraries. Concept development, technical development, evaluation and UX implications, and financial considerations are presented.

Published
2018

5. A Comparison of Dynamics in Major- and Minor-key Works

Author

Ben Turner and David Huron

Subjects
music, minor key, sadness, loudness, speech prosody, Music, M1-5000
Abstract

An analysis of dynamic markings in 24 paired preludes in major and minor keys shows that the minor mode is associated with a generally lower dynamic level than the major mode. The results are consistent with observations in speech prosody, where sad or depressed speakers show reduced acoustic energy compared with normal or happy speakers.

Published
2008
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6. QueF-Like, a Non-Homologous Archaeosine Synthase from the Crenarchaeota

Author

Adriana Bon Ramos, Lide Bao, Ben Turner, Valérie de Crécy-Lagard, and Dirk Iwata-Reuyl

Subjects
archaeosine, biosynthesis, modified nucleoside, tunneling-fold superfamily, amidinotransferase, Microbiology, QR1-502
Abstract

Archaeosine (G+) is a structurally complex modified nucleoside ubiquitous to the Archaea, where it is found in the D-loop of virtually all archaeal transfer RNA (tRNA). Its unique structure, which includes a formamidine group that carries a formal positive charge, and location in the tRNA, led to the proposal that it serves a key role in stabilizing tRNA structure. Although G+ is limited to the Archaea, it is structurally related to the bacterial modified nucleoside queuosine, and the two share homologous enzymes for the early steps of their biosynthesis. In the Euryarchaeota, the last step of the archaeosine biosynthetic pathway involves the amidation of a nitrile group on an archaeosine precursor to give formamidine, a reaction catalyzed by the enzyme Archaeosine Synthase (ArcS). Most Crenarchaeota lack ArcS, but possess two proteins that inversely distribute with ArcS and each other, and are implicated in G+ biosynthesis. Here, we describe biochemical studies of one of these, the protein QueF-like (QueF-L) from Pyrobaculum calidifontis, that demonstrate the catalytic activity of QueF-L, establish where in the pathway QueF-L acts, and identify the source of ammonia in the reaction.

Published
2017
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10. Using framework analysis to understand multiple stakeholders’ views of vocational rehabilitation following acquired brain injury

Author

Venerina Johnston, Charlotte Brakenridge, Donna Valiant, Charmaine Leow Kai Ling, Nicole Andrews, Elise M. Gane, Ben Turner, Melissa Kendall, and Ray Quinn

Subjects
Speech and Hearing, Behavioral Neuroscience, Neuropsychology and Physiological Psychology, Neurology, Cognitive Neuroscience, Neurology (clinical)
Abstract

Purpose: To explore how vocational rehabilitation (VR) is currently delivered for individuals with acquired brain injury (ABI) across multiple stakeholder groups and identify areas for improvement in service delivery using the Consolidated Framework for Implementation Research (CFIR). Methods: Seven focus groups were conducted with rehabilitation clinicians; outreach providers, insurers/regulators, VR providers and disability employment service providers (n = 44) experienced in VR of individuals with ABI. All groups were audio-recorded and transcribed verbatim. Data analysis was guided by the CFIR constructs. Results: All stakeholder groups believed they offered quality VR interventions given available resources and legislation, but many clients fell through the ‘cracks’. Themes that were identified included: a) number and complexity of systems supporting VR; b) fractured communication across systems, c) lack of knowledge by both stakeholders and clients in navigating systems, d) lack of expertise in supporting the vocational needs of clients with ABI and e) perceived limited awareness of ABI by employers. Conclusion: Stakeholders and clients need support to navigate Australia’s complex VR pathways. Limited specialist ABI clinicians, VR providers and disability employment services were identified as barriers for effective VR. Domains of the CFIR were appropriate for organising and understanding how VR is delivered.

Published
2022
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11. Rotational Modulation of Spectroscopic Zeeman Signatures in Low-mass Stars

Author

Ryan C Terrien, Allison Keen, Katy Oda, Winter Parts(they/them), Guðmundur Stefánsson, Suvrath Mahadevan, Paul Robertson, Joe P. Ninan, Corey Beard, Chad F. Bender, William D. Cochran, Katia Cunha, Scott A. Diddams, Connor Fredrick, Samuel Halverson, Fred Hearty, Adam Ickler, Shubham Kanodia, Jessica E. Libby-Roberts, Jack Lubin, Andrew J. Metcalf, Freja Olsen, Lawrence W. Ramsey, Arpita Roy, Christian Schwab, Verne V. Smith, and Ben Turner

Published
2022
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13. Normalising interdisciplinary role-based goal setting in inpatient brain injury rehabilitation: reflections and recommendations of clinicians

Author

Emmah Doig, Sarah Prescott, Valerie Pick, Ben Turner, Sameera Suleman, David Douglas, and Michele Foster

Subjects
Rehabilitation
Abstract

Person-centred goal setting with people with brain injury, by interdisciplinary teams has benefits including improved communication between patients, families and clinicians, person-centred care, and improved engagement in rehabilitation. Exploring the experiences of team members who have adopted interdisciplinary, person-centred goal setting may assist in understanding what is needed to implement this complex, core component of rehabilitation practice. This study explored experiences of clinicians working in an extended inpatient brain injury rehabilitation unit about implementing a role-based goal planning approach within an interdisciplinary team. Semi-structured interviews with 13 clinicians working at the rehabilitation unit explored their experiences about the cognitive participation and collective actions required to carry out the practice, with data analysed using inductive content analysis guided by Normalisation Process Theory. Three primary themes were identified: putting the person at the centre, accepting the mind-shift to participation focused goals and working collaboratively. This study has elucidated some key processes that occurred and were necessary to carry out goal setting. A mind-shift towards holistic, participation-focussed goal setting was described as “unlearning” discipline-specific goal setting. Development and ownership by the team, acceptance of team members and willingness to share, and structured processes and resources were necessary.IMPLICATIONS FOR REHABILITATIONNormalising interdisciplinary role-based goal setting in multi-professional teams requires a mind-shift away from traditional, discipline-specific goal setting.Implementation of interdisciplinary, collaborative team goal setting within health service settings requires collective actions including collaborative working by team members, structured processes including organised time for collaborative team and family meetings, practical resources and training to support processes.Clinicians perceived the goal setting approach to put the person at the centre resulting in a deep understanding of the person, shared understanding, and motivation for rehabilitation. Normalising interdisciplinary role-based goal setting in multi-professional teams requires a mind-shift away from traditional, discipline-specific goal setting. Implementation of interdisciplinary, collaborative team goal setting within health service settings requires collective actions including collaborative working by team members, structured processes including organised time for collaborative team and family meetings, practical resources and training to support processes. Clinicians perceived the goal setting approach to put the person at the centre resulting in a deep understanding of the person, shared understanding, and motivation for rehabilitation.

Published
2022
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15. 'ABOVE AND BEYOND THE MARKET'

Author

Ben Turner

Subjects
Cultural Studies, Philosophy, Social reproduction, Politics, Literature and Literary Theory, Work (electrical), Environmental ethics, Sociology, Conservatism, Philosophy of technology
Abstract

Assessments of the impact of automation often emphasize the need to “denaturalize” work. To what extent is denaturalization successful in separating proposals regarding the future of work from exis...

Published
2021
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16. Perioperative Care of Children with Severe Neurological Impairment and Neuromuscular Scoliosis

Author

Giuliana C, Antolovich, Monica S, Cooper, Michael B, Johnson, Kris, Lundine, Yi, Yang, Katherine, Frayman, Moya, Vandeleur, Ingrid, Sutherland, Donna, Peachey, Tali, Gadish, Ben, Turner, and Adrienne, Harvey

Abstract

Neuromuscular scoliosis is a common feature in children with severe neurological impairment (SNI), including those with severe cerebral palsy. Surgical correction of scoliosis is the mainstay of treatment. This group of patients also have associated medical complexity. The complication rates post-surgery are high, although, for many, they are worth the risk. There are currently no published practice guidelines or care pathways for children with SNI who are undergoing scoliosis corrective surgery. In response to the high uptake of this surgery, coupled with the expected complication rates, our hospital established a perioperative clinic. The purpose of this paper is to describe our perioperative approach. This clinic has developed into a service beyond perioperative care and, with the collaborative meeting, enables shared decision-making to identify the right candidate for surgery. The process involves surgical expertise, understanding the family and child at the centre, and optimisation of medical care pre- and post-surgery. In this paper, we describe the process in a step-by-step manner. We provide clinical vignettes, as well as the proformas that we use, and we highlight the benefits of the team-based process.

Published
2022

17. Predictive Factors for Magnetic Resonance Imaging Changes Suggestive of Demyelination in Adult Patients with Uveitis Scanned Prior to Commencing Adalimumab Therapy

Author

Priyanka Sanghi, Joshua Luis, Sofia Ajamil, Ian YL Yeung, Edward Hindle, Selina Sandhu, Said Hassan, Ben Turner, Angela Rees, and Mark Westcott

Subjects
Ophthalmology, Immunology and Allergy
Abstract

To report the predictive clinical factors for abnormal magnetic resonance imaging (MRI) scans suggestive of demyelination by analysis of MRI's performed for adult non-infectious uveitic patients prior to commencing adalimumab therapy.Retrospective case review of 240 patients was conducted in a single tertiary institution between November 2017 and March 2020. Aetiology of underlying disease, clinical characteristics, and MRI outcomes were analysed.The presence of bilateral idiopathic intermediate uveitis (IIU) (p = .0048) and neurological symptoms (p = .028) were highly predictive of an abnormal MRI strongly suggestive of demyelination (MRSSD); 5 out of 64 scans (7.8%) with these clinical characteristics had MRSSD.Tumor necrosis factor antagonist-induced demyelination is a concern in adalimumab use. We propose an MRI screening protocol to identify those at high risk of demyelination; positive results can be maximised by screening all patients with IIU and those with neurological symptoms.

Published
2022

18. Introduction: Why Should Political Theorists Care About Work?

Author

Lucas Van Milders and Ben Turner

Subjects
Literature and Literary Theory, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), JC, Public concern, Environmental ethics, General Medicine, Education, Politics, Social reproduction, Precarity, Work (electrical), Political philosophy, Sociology
Abstract

Even though the future of work has become a significant public concern, political theory has not yet considered work to be a central concept within the discipline. The five papers in this symposium provide a range of perspectives on what it means to take work seriously within political thought. This introduction will give an account of why work should be considered as important by political theorists, contextualize the broader landscape into which these papers intervene (characterized by the issues of automation, precarity, and social reproduction), and situate them within existing writing on work within political theory.

Published
2021
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19. Effect of a novel pharmacist-led reporting system on appropriate use of direct-acting oral anticoagulants (DOACs) in a patient-centered medical home

Author

Ben Turner, Jonathan Hughes, Allyson Wunderlich, Melissa Ragheb, and Toni Darnell

Subjects
Adult, Male, Medical home, medicine.medical_specialty, Psychological intervention, Pharmacist, Administration, Oral, Hemorrhage, 030204 cardiovascular system & hematology, Pharmacists, 03 medical and health sciences, 0302 clinical medicine, Ambulatory care, Patient-Centered Care, medicine, Humans, Medication Errors, 030212 general & internal medicine, Dosing, Medical prescription, Intensive care medicine, Qualitative Research, Aged, Aged, 80 and over, business.industry, Hematology, Middle Aged, Drug therapy problems, Prescriptions, Informatics, Female, Cardiology and Cardiovascular Medicine, business, Factor Xa Inhibitors
Abstract

Recent analyses demonstrate roughly 16-24% of patients taking direct-acting oral anticoagulants (DOACs) are prescribed an inappropriate dose, exposing patients to increased risk of thrombosis or bleeding. The use of reporting systems in the outpatient setting can efficiently identify potential medication errors and safety concerns. The purpose of this study was to evaluate the effect of a novel pharmacist-driven reporting system on appropriate prescribing of DOACs in the outpatient setting. This single-center qualitative study was conducted within a patient-centered medical home (PCMH). Reports were generated monthly to include all new DOAC prescriptions. Branching logic and filters were utilized within a secure web application to make the reporting process more efficient and identify regimens needing an intervention. Pharmacists reviewed the regimens populated by filters and made recommendations to prescribers as appropriate. The number of interventions proposed was captured as the primary outcome. Secondary outcomes include the nature of drug therapy problems identified and number of interventions accepted by prescribers. A total of 107 patients were analyzed for appropriateness from November 2017 to February 2019. Of the regimens included for review, 15 regimens were identified as potentially inappropriate. The nature of drug therapy problems identified include under dosing (4.25%), overdosing (2.13%), correction of documentation (2.13%), clarification of indication (3.19%), and ordering laboratory studies (3.19%). Of the interventions recommended, fourteen (93%) were accepted. Pharmacists integrated in a PCMH are well positioned to monitor and resolve DOAC drug therapy problems using local clinical reports.

Published
2020
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20. Acquiring Sustainable, Efficient High-Resolution Seismic Data for Geothermal Exploration in an Urban Environment

Author

Nick Tranter, Richard de Kunder, Ben Turner, and Guy Drijkoningen

Subjects
Geophysics
Abstract

The overall conditions under which geophysical data are being acquired have changed over the past five years due to the global economy combined with an increased emphasis on low environmental impact sustainability and safety. For land seismic acquisition, minimizing land disturbance, reducing CO2 emissions and increasing crew safety are key motivators to use innovations that drastically change conventional land seismic acquisition methods. One of the sources proven to do this is the eVibe developed by Seismic Mechatronics B V. They were recently contracted to undertake an urban seismic program utilizing their proprietary eVibe source in combination with Stryde Nodes. The seismic survey was acquired in one of the largest cities in the Netherlands, without the need for permits. Being able to minimize environmental impact, to reach a high safety standard and to acquire high-quality data in a noisy urban environment with the used technology made this project a success. This paper compares the results achieved by the Storm10 eVibe in combination with Stryde nodes to results previously obtained by an explosive survey. We show that the results are technically superior, with the eVibe and the Stryde Nodes proving far better suited to acquiring seismic data within this challenging and restrictive urban environment.

Published
2022

21. Ofatumumab versus Teriflunomide in Multiple Sclerosis

Author

Hauser S. L., Bar-Or A., Cohen J. A., Comi G., Correale J., Coyle P. K., Cross A. H., de Seze J., Leppert D., Montalban X., Selmaj K., Wiendl H., Kerloeguen C., Willi R., Li B., Kakarieka A., Tomic D., Goodyear A., Pingili R., Haring D. A., Ramanathan K., Merschhemke M., Kappos L., Stephen L Hauser, Ludwig Kappos, Amit Bar-Or, Jeffrey A Cohen, Giancarlo Comi, Jorge Correale, Patricia K Coyle, Anne Cross, Jerome de Seze, Xavier Montalban, Krzysztof Selmaj, Heinz Wiendl, Stephen C Reingold, Garry R Cutter, Thomas Doerner, Hans-Peter Hartung, Per Soelberg Sørensen, Israel Steiner, Jerry S Wolinsky, Carlos Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana Liwacki, Jeannette Lechner-Scott, John Parratt, Suzanne Hodgkinson, Eva-Maria Maida, Fritz Leutmezer, Barbara Willekens, Bart Van Wijmeersch, Guy Laureys, Jo Caekebeke, Karine Geens, Ludo Vanopdenbosch, Olivier Deryck, Valerie Delvaux, Vincent Van Pesch, Ivan Milanov, Ivaylo Tarnev, Lyubomir Haralanov, Maria Manova Slavova, Penko Shotekov, Francois Emond, Francois Grandmaison, Francois Jacques, Liesly Lee, Marie Sarah Gagne Brosseau, Mark Freedman, Martin Cloutier, Robert Carruthers, Sarah Morrow, Yves Lapierre, Anton Vladic, Hana Bokun, Igor Antoncic, Marija Bosnjak Pasic, Mario Habek, Silva Butkovic Soldo, Vladimira Vuletic, Alena Martinkova, Eva Meluzinova, Ivana Stetkarova, Jan Mares, Jolana Markova, Marta Vachova, Martin Valis, Michaela Tyblova, Michal Dufek, Ondrej Skoda, Pavel Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina Svendsen, Mads Ravnborg, Peter Vestergaard Rasmussen, Katrin Gross-Paju, Sulev Haldre, Juha Pekka Eralinna, Marja-Liisa Sumelahti, Bruno Brochet, Celine Louapre, Christine Lebrun-Frenay, David Axel Laplaud, Gilles Edan, Giovanni Castelnovo, Marc Debouverie, Patrick Vermersch, Pierre Clavelou, Pierre Labauge, Achim Berthele, Aiden Haghikia, Anselm Kornhuber, Arnfin Bergmann, Benedikt Frank, Birte Elias-Hamp, Bjoern Tackenberg, Brigitte Wildemann, Erik Strauss, Eugen Schlegel, Florian Then Bergh, Gereon Nelles, Hayrettin Tumani, Karl-Otto Sigel, Martin Stangel, Matthias Boehringer, Olaf Martin Hoffmann, Patrick Oschmann, Reinhard Hohlfeld, Silke Walter, Sylvia Menck, Till Sprenger, Tjalf Ziemssen, Veit Ulrich Becker, Vera Straeten, Konstantinos Kilidireas, Konstantinos Voumvourakis, Nikolaos Fakas, Nikolaos Grigoriadis, Agnes Koves, Csilla Rozsa, Krisztina Kovacs, Laszlo Vecsei, Satori Maria, Zita Biro, Anshu Rohatgi, Dheeraj Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha Pandit, Meena Angamuthu Kanikannan, Pahari Ghosh, Rahul Chakor, Rahul Kulkarni, Roopkumar Gursahani, Sangeeta Ravat, Srinivasa Rangasetty, Suresh Kumar, Alla Shifrin, Arnon Karni, Radi Shahien, Ron Milo, Antonio Uccelli, Carlo Pozzilli, Francesco Sacca, Giacomo Lus, Girolama Alessandra Marfia, Laura Brambilla, Marco Salvetti, Massimo Filippi, Mauro Zaffaroni, Paolo Gallo, Silvia Rossi, Simona Bonavita, Valeria Studer, Andrejs Millers, Guntis Karelis, Jolanta Kalnina, Dalia Mickeviciene, Rasa Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs Wokke, Bob W Van Oosten, Peter Van Domburg, Raymond Hupperts, Rogier Q Hintzen, Astrid Edland, Cesar Castaneda, Julio Perez, Martin Gavidia, Andrzej Wiak, Bartosz Karaszewski, Elzbieta Jasinska, Halina Bartosik Psujek, Iwona Jastrzebska, Jaroslaw Slawek, Maciej Maciejowski, Miroslaw Dziki, Monika Adamczyk Sowa, Robert Bonek, Waldemar Fryze, Ana Martins Da Silva, Angela Timoteo, Antonio Vasco Salgado, Carlos Capela, Carlos Veira, Filipe Correia, Joao Cerqueira, Joao De Sa, Livia De Sousa, Raquel Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon Kurca, Georgi Krastev, Miroslav Brozman, Peter Koleda, Peter Turcani, Peter Valkovic, Viera Hancinova, Vladimir Donath, Chris Retief, Michael Isaacs, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik Piehl, Jan Lycke, Chiara Zecca, Tobias Derfuss, Thy-Sheng Lin, Somsak Tiamkao, Ayse Nur Yuceyar, Aysun Soysal, Belgin Petek Balci, Cavit Boz, Husnu Efendi, Murat Terzi, Serhan Sevim, Serkan Ozakbas, Andrew Gale, Ben Turner, David Barnes, David Paling, Eli Silber, James Overell, Matthew Craner, Aaron Carlson, Adam Wolff, Adaeze Onuoha, Adnan Subei, Ahmad Ata, Aimee Borazanci, Akram Dastagir, Alberto Vasquez, Alison Brooke Allen, Andrew P Keegan, Angel Carrasco, Angel R Chinea Martinez, Ann Bass, Annette Okai, April Erwin, Ariel Antezana-Antezana, Barbara Green, Bharathy E Sundaram, Bhupendra Khatri, Bhupesh Dihenia, Bogdan Gheorghiu, Brian Costell, Brian Steingo, Bruce L Hughes, Carrie M Hersh, Christopher Laganke, Christopher Luzzio, Corey Ford, Craig Edward Herrman, Craig Senzon, Cynthia Huffman, Daniel R Wynn, David D O Bear, David Lesch, David H Mattson, David Weisman, Deborah A Burke, Dennis W Dietrich, Deren Huang, Derrick Robertson, Djamchid Lotfi, Don Joseph Alfonso, Dusan Stefoski, Edward J Fox, Emily Pharr, Enrique Alvarez, Evanthia Bernitsas, Faria Amjad, Gabriel Pardo, Geoffrey Eubank, Gerald Mcintosh, Giles F Crowell, Hemanth Rao, J Michael Hemphill, Jack H Florin, Jacqueline Nicholas, James Napier, James Scott, Jason M Silversteen, Javier Vasallo, Jean-Raphael Schneider, Jeanette Wendt, Jeffrey Cohen, Jeffrey Gross, Jeffrey Groves, Jeffrey Kaplan, Jessica Stulc, Joanna A Cooper, John Foley, John Scagnelli, Jonathan C Calkwood, Jose Pizarro Otero, Jose Rafecas, Joshua Katz, Juliette S Saad, Katherine Standley, Keith Edwards, Kenneth Sharlin, Khurram Bashir, Kimberly Wagner, Kore Liow, Larry Lee Blankenship Jr, Laszlo Mate, Liliana Montoya, Lon D Lynn, Mark Agius, Mark Cascione, Mark Allan Goldstein, Mark Janicki, Martin R Bialow, Mary Denise Hughes, Matthew J Baker, Michelle Apperson, Michelle B Kuczma, M Mateo Paz Soldan, Mirela Cerghet, Nathaniel Robb Whaley, Paul K Winner, Pavle Repovic, Praful Kelkar, Romero Rekha Pillai, Ricardo Ayala, Richard Sater, Randall Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert Naismith, Ronald S Murray, Samuel Hunter, Sara Qureshi, Sharon Lynch, Sibyl Wray, Silvia R Delgado, Stacy Donlon, Stanley Cohan, Stanya Smith, Stuart James Shafer, Susan Azalone, Susan Hibbs, Tamara A Miller, Thomas Giancarlo, Troy Desai, Varun K Saxena, Virginia Simnad, William David Honeycutt, William Logan, William E McElveen, William Wagner, University of California [San Francisco] (UCSF), University of California, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Cleveland Clinic, IRCCS Ospedale San Raffaele [Milan, Italy], Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), 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, University Hospital Basel [Basel], Vall d'Hebron University Hospital [Barcelona], University of Warmia and Mazury [Olsztyn], University of Münster, Novartis Pharma S.A.S., Novartis Pharmaceuticals, University of Basel (Unibas), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Willekens, Barbara, ASCLEPIOS I and ASCLEPIOS II Trial Groups, Hauser, S. L., Bar-Or, A., Cohen, J. A., Comi, G., Correale, J., Coyle, P. K., Cross, A. H., de Seze, J., Leppert, D., Montalban, X., Selmaj, K., Wiendl, H., Kerloeguen, C., Willi, R., Li, B., Kakarieka, A., Tomic, D., Goodyear, A., Pingili, R., Haring, D. A., Ramanathan, K., Merschhemke, M., Kappos, L., Asclepios, I and ASCLEPIOS II Trial Group, Filippi, M, L Hauser, Stephen, Kappos, Ludwig, Bar-Or, Amit, A Cohen, Jeffrey, Comi, Giancarlo, Correale, Jorge, K Coyle, Patricia, Cross, Anne, de Seze, Jerome, Montalban, Xavier, Selmaj, Krzysztof, Wiendl, Heinz, C Reingold, Stephen, R Cutter, Garry, Doerner, Thoma, Hartung, Hans-Peter, Soelberg Sørensen, Per, Steiner, Israel, S Wolinsky, Jerry, Ballario, Carlo, Calvo Vildoso, Christian, Gustavo Jose, Jorge, Haydee Deri, Norma, Liwacki, Susana, Lechner-Scott, Jeannette, Parratt, John, Hodgkinson, Suzanne, Maida, Eva-Maria, Leutmezer, Fritz, Van Wijmeersch, Bart, Laureys, Guy, Caekebeke, Jo, Geens, Karine, Vanopdenbosch, Ludo, Deryck, Olivier, Delvaux, Valerie, Van Pesch, Vincent, Milanov, Ivan, Tarnev, Ivaylo, Haralanov, Lyubomir, Manova Slavova, Maria, Shotekov, Penko, Emond, Francoi, Grandmaison, Francoi, Jacques, Francoi, Lee, Liesly, Sarah Gagne Brosseau, Marie, Freedman, Mark, Cloutier, Martin, Carruthers, Robert, Morrow, Sarah, Lapierre, Yve, Vladic, Anton, Bokun, Hana, Antoncic, Igor, Bosnjak Pasic, Marija, Habek, Mario, Butkovic Soldo, Silva, Vuletic, Vladimira, Martinkova, Alena, Meluzinova, Eva, Stetkarova, Ivana, Mares, Jan, Markova, Jolana, Vachova, Marta, Valis, Martin, Tyblova, Michaela, Dufek, Michal, Skoda, Ondrej, Hradilek, Pavel, Voldsgaard Jensen, Ana, Hvilsted Nielsen, Helle, Svendsen, Kristina, Ravnborg, Mad, Vestergaard Rasmussen, Peter, Gross-Paju, Katrin, Haldre, Sulev, Pekka Eralinna, Juha, Sumelahti, Marja-Liisa, Brochet, Bruno, Louapre, Celine, Lebrun-Frenay, Christine, Axel Laplaud, David, Edan, Gille, Castelnovo, Giovanni, Debouverie, Marc, Vermersch, Patrick, Clavelou, Pierre, Labauge, Pierre, Berthele, Achim, Haghikia, Aiden, Kornhuber, Anselm, Bergmann, Arnfin, Frank, Benedikt, Elias-Hamp, Birte, Tackenberg, Bjoern, Wildemann, Brigitte, Strauss, Erik, Schlegel, Eugen, Then Bergh, Florian, Nelles, Gereon, Tumani, Hayrettin, Sigel, Karl-Otto, Stangel, Martin, Boehringer, Matthia, Martin Hoffmann, Olaf, Oschmann, Patrick, Hohlfeld, Reinhard, Walter, Silke, Menck, Sylvia, Sprenger, Till, Ziemssen, Tjalf, Ulrich Becker, Veit, Straeten, Vera, Kilidireas, Konstantino, Voumvourakis, Konstantino, Fakas, Nikolao, Grigoriadis, Nikolao, Koves, Agne, Rozsa, Csilla, Kovacs, Krisztina, Vecsei, Laszlo, Maria, Satori, Biro, Zita, Rohatgi, Anshu, Khurana, Dheeraj, Durai Pandian, Jeyaraj, Dev Mukherji, Joy, Pandit, Lekha, Angamuthu Kanikannan, Meena, Ghosh, Pahari, Chakor, Rahul, Kulkarni, Rahul, Gursahani, Roopkumar, Ravat, Sangeeta, Rangasetty, Srinivasa, Kumar, Suresh, Shifrin, Alla, Karni, Arnon, Shahien, Radi, Milo, Ron, Uccelli, Antonio, Pozzilli, Carlo, Sacca, Francesco, Lus, Giacomo, Alessandra Marfia, Girolama, Brambilla, Laura, Salvetti, Marco, Filippi, Massimo, Zaffaroni, Mauro, Gallo, Paolo, Rossi, Silvia, Bonavita, Simona, Studer, Valeria, Millers, Andrej, Karelis, Gunti, Kalnina, Jolanta, Mickeviciene, Dalia, Kizlaitiene, Rasa, Carbajal Ramirez, Angelica, Jose Lopez Prieto, Juan, Wokke, Beatrij, W Van Oosten, Bob, Van Domburg, Peter, Hupperts, Raymond, Q Hintzen, Rogier, Edland, Astrid, Castaneda, Cesar, Perez, Julio, Gavidia, Martin, Wiak, Andrzej, Karaszewski, Bartosz, Jasinska, Elzbieta, Bartosik Psujek, Halina, Jastrzebska, Iwona, Slawek, Jaroslaw, Maciejowski, Maciej, Dziki, Miroslaw, Adamczyk Sowa, Monika, Bonek, Robert, Fryze, Waldemar, Martins Da Silva, Ana, Timoteo, Angela, Vasco Salgado, Antonio, Capela, Carlo, Veira, Carlo, Correia, Filipe, Cerqueira, Joao, De Sa, Joao, De Sousa, Livia, Gouveia, Raquel, Sergeevna Agafina, Alina, Naumovna Belova, Anna, Viktorovich Sazonov, Deni, Pokhabov, Dmitry, Igorevna Kairbekova, Ekaterina, Gennadievna Arefieva, Elena, Axatovich Khabirov, Farit, Vyacheslavovich Litvinenko, Igor, Stolyarov, Igor, Aleksandrovna Sokolova, Irina, Ivanovna Volkova, Larisa, Vafaevna Davydovskaya, Maria, Nikolaevna Zaharova, Maria, Alekseevna Malkova, Nadezhda, Agafonovna Totolyan, Natalia, Vasilievich Dorogov, Nikolay, Anatolievna Sivertseva, Stella, Kurca, Egon, Krastev, Georgi, Brozman, Miroslav, Koleda, Peter, Turcani, Peter, Valkovic, Peter, Hancinova, Viera, Donath, Vladimir, Retief, Chri, Isaacs, Michael, Saiz Hinarejos, Albert, Rodriguez Antigüedad, Alfredo, Casanova Estruch, Bonaventura, Oreja-Guevara, Celia, Reig Rosello, Gemma, Carlos Alvarez Cermeño, Jose, Martinez Rodriguez, Jose, Meca Lallana, Jose, Antonio Garcia Merino, Juan, Forero Diaz, Lucia, Costa Frossard Franca, Lucienne, Querol Gutierrez, Lui, Ramio Torrenta, Llui, Serrano Castro, Pedro, Arroyo Gonzalez, Rafael, Eichau Madueño, Sara, Martinez Yelamos, Sergio, Castillo Trivino, Tamara, Meca Lallana, Virgina, Montalban Gairin, Xaviere, Piehl, Fredrik, Lycke, Jan, Zecca, Chiara, Derfuss, Tobia, Lin, Thy-Sheng, Tiamkao, Somsak, Nur Yuceyar, Ayse, Soysal, Aysun, Petek Balci, Belgin, Boz, Cavit, Efendi, Husnu, Terzi, Murat, Sevim, Serhan, Ozakbas, Serkan, Gale, Andrew, Turner, Ben, Barnes, David, Paling, David, Silber, Eli, Overell, Jame, Craner, Matthew, Carlson, Aaron, Wolff, Adam, Onuoha, Adaeze, Subei, Adnan, Ata, Ahmad, Borazanci, Aimee, Dastagir, Akram, Vasquez, Alberto, Brooke Allen, Alison, P Keegan, Andrew, Carrasco, Angel, R Chinea Martinez, Angel, Bass, Ann, Okai, Annette, Erwin, April, Antezana-Antezana, Ariel, Green, Barbara, E Sundaram, Bharathy, Khatri, Bhupendra, Dihenia, Bhupesh, Gheorghiu, Bogdan, Costell, Brian, Steingo, Brian, L Hughes, Bruce, M Hersh, Carrie, Laganke, Christopher, Luzzio, Christopher, Ford, Corey, Edward Herrman, Craig, Senzon, Craig, Huffman, Cynthia, R Wynn, Daniel, O Bear, David D, Lesch, David, H Mattson, David, Weisman, David, A Burke, Deborah, W Dietrich, Denni, Huang, Deren, Robertson, Derrick, Lotfi, Djamchid, Joseph Alfonso, Don, Stefoski, Dusan, J Fox, Edward, Pharr, Emily, Alvarez, Enrique, Bernitsas, Evanthia, Amjad, Faria, Pardo, Gabriel, Eubank, Geoffrey, Mcintosh, Gerald, F Crowell, Gile, Rao, Hemanth, Michael Hemphill, J, H Florin, Jack, Nicholas, Jacqueline, Napier, Jame, Scott, Jame, M Silversteen, Jason, Vasallo, Javier, Schneider, Jean-Raphael, Wendt, Jeanette, Cohen, Jeffrey, Gross, Jeffrey, Groves, Jeffrey, Kaplan, Jeffrey, Stulc, Jessica, A Cooper, Joanna, Foley, John, Scagnelli, John, C Calkwood, Jonathan, Pizarro Otero, Jose, Rafecas, Jose, Katz, Joshua, S Saad, Juliette, Standley, Katherine, Edwards, Keith, Sharlin, Kenneth, Bashir, Khurram, Wagner, Kimberly, Liow, Kore, Lee Blankenship Jr, Larry, Mate, Laszlo, Montoya, Liliana, D Lynn, Lon, Agius, Mark, Cascione, Mark, Allan Goldstein, Mark, Janicki, Mark, R Bialow, Martin, Denise Hughes, Mary, J Baker, Matthew, Apperson, Michelle, B Kuczma, Michelle, Mateo Paz Soldan, M, Cerghet, Mirela, Robb Whaley, Nathaniel, K Winner, Paul, Repovic, Pavle, Kelkar, Praful, Rekha Pillai, Romero, Ayala, Ricardo, Sater, Richard, Trudell, Randall, Fairborn Armstrong, Robert, Thomas Nahouraii, Robert, Naismith, Robert, S Murray, Ronald, Hunter, Samuel, Qureshi, Sara, Lynch, Sharon, Wray, Sibyl, R Delgado, Silvia, Donlon, Stacy, Cohan, Stanley, Smith, Stanya, James Shafer, Stuart, Azalone, Susan, Hibbs, Susan, A Miller, Tamara, Giancarlo, Thoma, Desai, Troy, K Saxena, Varun, Simnad, Virginia, David Honeycutt, William, Logan, William, E McElveen, William, Wagner, William, Stephen, L Hauser, Ludwig, Kappo, Amit, Bar-Or, Jeffrey, A Cohen, Giancarlo, Comi, Jorge, Correale, Patricia, K Coyle, Anne, Cro, Jerome de Seze, Xavier, Montalban, Krzysztof, Selmaj, Heinz, Wiendl, Stephen, C Reingold, Garry, R Cutter, Thomas, Doerner, Hans-Peter, Hartung, Per Soelberg Sørensen, Israel, Steiner, Jerry, S Wolinsky, Carlos, Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana, Liwacki, Jeannette, Lechner-Scott, John, Parratt, Suzanne, Hodgkinson, Eva-Maria, Maida, Fritz, Leutmezer, Barbara, Willeken, Bart Van Wijmeersch, Guy, Laurey, Karine, Geen, Ludo, Vanopdenbosch, Olivier, Deryck, Valerie, Delvaux, Vincent Van Pesch, Ivan, Milanov, Ivaylo, Tarnev, Lyubomir, Haralanov, Maria Manova Slavova, Penko, Shotekov, Francois, Emond, Francois, Grandmaison, Francois, Jacque, Liesly, Lee, Marie Sarah Gagne Brosseau, Mark, Freedman, Martin, Cloutier, Robert, Carruther, Sarah, Morrow, Yves, Lapierre, Anton, Vladic, Hana, Bokun, Igor, Antoncic, Marija Bosnjak Pasic, Mario, Habek, Silva Butkovic Soldo, Vladimira, Vuletic, Alena, Martinkova, Eva, Meluzinova, Ivana, Stetkarova, Jan, Mare, Jolana, Markova, Marta, Vachova, Martin, Vali, Michaela, Tyblova, Michal, Dufek, Ondrej, Skoda, Pavel, Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina, Svendsen, Mads, Ravnborg, Peter Vestergaard Rasmussen, Katrin, Gross-Paju, Sulev, Haldre, Juha Pekka Eralinna, Marja-Liisa, Sumelahti, Bruno, Brochet, Celine, Louapre, Christine, Lebrun-Frenay, David Axel Laplaud, Gilles, Edan, Giovanni, Castelnovo, Marc, Debouverie, Patrick, Vermersch, Pierre, Clavelou, Pierre, Labauge, Achim, Berthele, Aiden, Haghikia, Anselm, Kornhuber, Arnfin, Bergmann, Benedikt, Frank, Birte, Elias-Hamp, Bjoern, Tackenberg, Brigitte, Wildemann, Erik, Strau, Eugen, Schlegel, Florian Then Bergh, Gereon, Nelle, Hayrettin, Tumani, Karl-Otto, Sigel, Martin, Stangel, Matthias, Boehringer, Olaf Martin Hoffmann, Patrick, Oschmann, Reinhard, Hohlfeld, Silke, Walter, Sylvia, Menck, Till, Sprenger, Tjalf, Ziemssen, Veit Ulrich Becker, Vera, Straeten, Konstantinos, Kilidirea, Konstantinos, Voumvouraki, Nikolaos, Faka, Nikolaos, Grigoriadi, Agnes, Kove, Csilla, Rozsa, Krisztina, Kovac, Laszlo, Vecsei, Satori, Maria, Zita, Biro, Anshu, Rohatgi, Dheeraj, Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha, Pandit, Meena Angamuthu Kanikannan, Pahari, Ghosh, Rahul, Chakor, Rahul, Kulkarni, Roopkumar, Gursahani, Sangeeta, Ravat, Srinivasa, Rangasetty, Suresh, Kumar, Alla, Shifrin, Arnon, Karni, Radi, Shahien, Ron, Milo, Antonio, Uccelli, Carlo, Pozzilli, Sacca', Francesco, Giacomo, Lu, Girolama Alessandra Marfia, Laura, Brambilla, Marco, Salvetti, Massimo, Filippi, Mauro, Zaffaroni, Paolo, Gallo, Silvia, Rossi, Simona, Bonavita, Valeria, Studer, Andrejs, Miller, Guntis, Kareli, Jolanta, Kalnina, Dalia, Mickeviciene, Rasa, Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs, Wokke, Bob, W Van Oosten, Peter Van Domburg, Raymond, Huppert, Rogier, Q Hintzen, Astrid, Edland, Cesar, Castaneda, Julio, Perez, Martin, Gavidia, Andrzej, Wiak, Bartosz, Karaszewski, Elzbieta, Jasinska, Halina Bartosik Psujek, Iwona, Jastrzebska, Jaroslaw, Slawek, Maciej, Maciejowski, Miroslaw, Dziki, Monika Adamczyk Sowa, Robert, Bonek, Waldemar, Fryze, Ana Martins Da Silva, Angela, Timoteo, Antonio Vasco Salgado, Carlos, Capela, Carlos, Veira, Filipe, Correia, Joao, Cerqueira, Joao De Sa, Livia De Sousa, Raquel, Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry, Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor, Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon, Kurca, Georgi, Krastev, Miroslav, Brozman, Peter, Koleda, Peter, Turcani, Peter, Valkovic, Viera, Hancinova, Vladimir, Donath, Chris, Retief, Michael, Isaac, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia, Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik, Piehl, Jan, Lycke, Chiara, Zecca, Tobias, Derfu, Thy-Sheng, Lin, Somsak, Tiamkao, Ayse Nur Yuceyar, Aysun, Soysal, Belgin Petek Balci, Cavit, Boz, Husnu, Efendi, Murat, Terzi, Serhan, Sevim, Serkan, Ozakba, Andrew, Gale, Ben, Turner, David, Barne, David, Paling, Eli, Silber, James, Overell, Matthew, Craner, Aaron, Carlson, Adam, Wolff, Adaeze, Onuoha, Adnan, Subei, Ahmad, Ata, Aimee, Borazanci, Akram, Dastagir, Alberto, Vasquez, Alison Brooke Allen, Andrew, P Keegan, Angel, Carrasco, Angel, R Chinea Martinez, Ann, Ba, Annette, Okai, April, Erwin, Ariel, Antezana-Antezana, Barbara, Green, Bharathy, E Sundaram, Bhupendra, Khatri, Bhupesh, Dihenia, Bogdan, Gheorghiu, Brian, Costell, Brian, Steingo, Bruce, L Hughe, Carrie, M Hersh, Christopher, Laganke, Christopher, Luzzio, Corey, Ford, Craig Edward Herrman, Craig, Senzon, Cynthia, Huffman, Daniel, R Wynn, David D, O Bear, David, Lesch, David, H Mattson, David, Weisman, Deborah, A Burke, Dennis, W Dietrich, Deren, Huang, Derrick, Robertson, Djamchid, Lotfi, Don Joseph Alfonso, Dusan, Stefoski, Edward, J Fox, Emily, Pharr, Enrique, Alvarez, Evanthia, Bernitsa, Faria, Amjad, Gabriel, Pardo, Geoffrey, Eubank, Gerald, Mcintosh, Giles, F Crowell, Hemanth, Rao, J Michael Hemphill, Jack, H Florin, Jacqueline, Nichola, James, Napier, James, Scott, Jason, M Silversteen, Javier, Vasallo, Jean-Raphael, Schneider, Jeanette, Wendt, Jeffrey, Cohen, Jeffrey, Gro, Jeffrey, Grove, Jeffrey, Kaplan, Jessica, Stulc, Joanna, A Cooper, John, Foley, John, Scagnelli, Jonathan, C Calkwood, Jose Pizarro Otero, Jose, Rafeca, Joshua, Katz, Juliette, S Saad, Katherine, Standley, Keith, Edward, Kenneth, Sharlin, Khurram, Bashir, Kimberly, Wagner, Kore, Liow, Larry Lee Blankenship Jr, Laszlo, Mate, Liliana, Montoya, Lon, D Lynn, Mark, Agiu, Mark, Cascione, Mark Allan Goldstein, Mark, Janicki, Martin, R Bialow, Mary Denise Hughes, Matthew, J Baker, Michelle, Apperson, Michelle, B Kuczma, M Mateo Paz Soldan, Mirela, Cerghet, Nathaniel Robb Whaley, Paul, K Winner, Pavle, Repovic, Praful, Kelkar, Romero Rekha Pillai, Ricardo, Ayala, Richard, Sater, Randall, Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert, Naismith, Ronald, S Murray, Samuel, Hunter, Sara, Qureshi, Sharon, Lynch, Sibyl, Wray, Silvia, R Delgado, Stacy, Donlon, Stanley, Cohan, Stanya, Smith, Stuart James Shafer, Susan, Azalone, Susan, Hibb, Tamara, A Miller, Thomas, Giancarlo, Troy, Desai, Varun, K Saxena, Virginia, Simnad, William David Honeycutt, William, Logan, William, E McElveen, William, Wagner, University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Herrada, Anthony, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Male, MESH: Multiple Sclerosis, Relapsing-Remitting, T-Lymphocytes, Hydroxybutyrates, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Pharmacology, Relapsing-Remitting, MESH: Magnetic Resonance Imaging, chemistry.chemical_compound, 0302 clinical medicine, Teriflunomide, Monoclonal, MESH: Double-Blind Method, 030212 general & internal medicine, Humanized, MESH: Toluidines, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Subcutaneous, B-Lymphocyte, Brain, General Medicine, Magnetic Resonance Imaging, MESH: Crotonates, Crotonates, Pyrimidine metabolism, Disease Progression, Female, MESH: Disease Progression, Antibody, Human, Adult, Multiple Sclerosis, Toluidines, medicine.drug_class, Injections, Subcutaneous, Injections, Subcutaneou, Monoclonal antibody, Ofatumumab, Settore MED/26, Antibodies, Monoclonal, Humanized, Crotonate, Antibodies, Injections, 03 medical and health sciences, MESH: Brain, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, MESH: B-Lymphocytes, Nitriles, medicine, Humans, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, Multiple sclerosis, MESH: Injections, Subcutaneous, MESH: Adult, medicine.disease, MESH: Male, MESH: T-Lymphocytes, T-Lymphocyte, Multicenter study, chemistry, MESH: Antibodies, Monoclonal, Humanized, biology.protein, Human medicine, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

Published
2020
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22. Analysis of Vasopressor Discontinuation and the Incidence of Rebound Hypotension in Patients With Septic Shock

Author

Dalton Walsh, Meghan J. Garrett, Vishal N. Ooka, Christopher T. Buckley, and Ben Turner

Subjects
Pharmacology, Vasopressin, Septic shock, business.industry, Incidence (epidemiology), 030208 emergency & critical care medicine, Pharmacy, medicine.disease, Discontinuation, Norepinephrine (medication), 03 medical and health sciences, 0302 clinical medicine, Anesthesia, medicine, Pharmacology (medical), In patient, 030212 general & internal medicine, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract

Purpose: The purpose of this study was to examine the incidence of rebound hypotension in patients with septic shock requiring both norepinephrine and vasopressin infusions once discontinuation of 1 of these agents is warranted. Methods: A multicenter, retrospective study was conducted in 3 hospitals within a single health system between January 1, 2016, and December 31, 2017. The study population included adults, 18 years and older, diagnosed with septic shock and requiring concurrent infusions of norepinephrine and vasopressin. The primary outcome evaluated the incidence of rebound hypotension within 24 hours after the first vasopressor was discontinued. Secondary outcomes included intensive care unit length of stay, hospital length of stay, total vasopressor duration, and the time to rebound hypotension after first vasopressor discontinuation. Results: A total of 69 patients were included in the study, 38 in the vasopressin discontinued first group and 31 in the norepinephrine discontinued first group. Rebound hypotension occurred in 82% of patients in the vasopressin discontinued first group compared with 48% in the norepinephrine discontinued first group ( P = .004). No differences were observed in secondary outcomes, including intensive care unit or hospital length of stay, total vasopressor duration, or the time to rebound hypotension. Conclusions: Discontinuation of norepinephrine before vasopressin may lead to less incidence of rebound hypotension in patients with septic shock who require concurrent norepinephrine and vasopressin infusions. Similar to previous studies, this study found no difference in secondary outcomes.

Published
2019
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24. Exploring the lived return-to-work experience of individuals with acquired brain injury: use of vocational services and environmental, personal and injury-related influences

Author

Ray Quinn, Venerina Johnston, Melissa Kendall, Charlotte L. Brakenridge, Ben Turner, Charmaine Kai Ling Leow, and Donna Valiant

Subjects
Gerontology, Employment, 030506 rehabilitation, Traumatic brain injury, Rehabilitation, Cognition, Rehabilitation, Vocational, Service provider, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Return to Work, Work (electrical), Vocational education, Brain Injuries, medicine, Humans, Thematic analysis, Occupations, 0305 other medical science, Psychology, Acquired brain injury, 030217 neurology & neurosurgery, Qualitative research
Abstract

To explore work outcomes, vocational services, barriers and facilitators for returning to work in individuals with acquired brain injury (ABI) in Queensland, Australia and to identify areas for improvement. Ten semi-structured interviews were conducted with individuals with ABI (stroke, traumatic brain injury, tumour). Interviews were analysed using a realist thematic analysis approach. Participants either returned to the same work, different work, did not maintain work or did not have any work since their injury. Use of vocational services depended on participants' needs and insurance. Facilitators for return to work (RTW) were a supportive workplace and family, vocational rehabilitation that met the individual's needs, insurance coverage and self-motivation. Workplaces that were not understanding of brain injury, employment service providers who were unable to find work for participants, and physical and cognitive deficits were barriers to RTW. Workplaces, employment service providers and individuals require more information about the deficits associated with brain injury. The use and effectiveness of vocational services were variable across participants and depended on insurance coverage and needs. Barriers and facilitators for RTW were affected by both the environment and the individual. Implications for vocational rehabilitation were identified.Implications for RehabilitationA supportive workplace and family, and access to appropriate vocational rehabilitation are important environmental facilitators for RTW in individuals with ABI.Workplaces with a poor understanding of ABI and employment service providers unable to find work for individuals with ABI are environmental barriers to RTW.Workplaces, employment service providers and individuals with ABI require more information about the physical and cognitive deficits associated with ABI.Employment service providers need more training to develop comprehensive strategies to help individuals with ABI find new employment.

Published
2021

25. Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series

Author

Olga Ciccarelli, Richard Nicholas, Ben Turner, Ian H Gabriel, Eli Silber, Elijah Edward Rhone, Antonio Scalfari, Omar Malik, Varun Mehra, Paolo A. Muraro, Victoria Singh-Curry, Alice Mariottini, Majid Kazmi, Eduardo Olavarria, and Maria Pia Sormani

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Cohort Studies, Female, Hematopoietic Stem Cell Transplantation, Humans, London, Middle Aged, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting, Retrospective Studies, Transplantation, Autologous, Treatment Outcome, medicine.medical_treatment, Hematopoietic stem cell transplantation, Relapsing-Remitting, Internal medicine, Medicine, Transplantation, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Retrospective cohort study, medicine.disease, Clinical trial, Chronic Progressive, Cohort, Neurology (clinical), business, Autologous, Research Article, Cohort study
Abstract

ObjectiveTo examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting.MethodsThis was a retrospective cohort study of PwMS treated with AHSCT at 2 centers in London, UK, consecutively between 2012 and 2019 who had ≥6 months of follow-up or died at any time. Primary outcomes were survival free of multiple sclerosis (MS) relapses, MRI new lesions, and worsening of Expanded Disability Status Scale (EDSS) score. Adverse events rates were also examined.ResultsThe cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS. At baseline, the median EDSS score was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6–85 months). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of participants at 2 years and in 85% at 4 years. EDSS score progression–free survival (PFS) was 75% at 2 years and 65% at 4 years. Epstein-Barr virus reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplantation-related deaths within 100 days (2.5%), all after fluid overload and cardiac or respiratory failure.ConclusionsEfficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher.Classification of EvidenceThis study is rated Class IV because of the uncontrolled, open-label design.

Published
2021

27. β-lactam dosing strategies: Think before you push

Author

Nathaniel J. Rhodes, Gwendolyn M Pais, Ben Turner, Patrick J Kiel, Jason A. Roberts, Jiajun Liu, and Marc H. Scheetz

Subjects
0301 basic medicine, Microbiology (medical), Dose, Cefepime, 030106 microbiology, Population, Renal function, Microbial Sensitivity Tests, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Dosing, education, education.field_of_study, Bacteria, Dose-Response Relationship, Drug, business.industry, General Medicine, Anti-Bacterial Agents, Regimen, Infectious Diseases, Pharmacodynamics, Anesthesia, business, medicine.drug
Abstract

Objectives There has been interest in administering cefepime, a β-lactam antibiotic, via intravenous push (IVP) as a means to improve time to first-dose antibiotic and reduce cost; however, the downstream impacts on antibiotic exposure and pharmacodynamic efficacy need to be further evaluated. Methods This study used a population pharmacokinetic model for cefepime and simulated exposures to predict the pharmacodynamic (PD) effect for cefepime regimens administered via IVP or 30-minute intermittent infusion in adults with different renal functions. FDA-approved adult dosages of 1–2 g every 8 or 12 hours were compared. This study aimed to compare the absolute difference in pharmacodynamic probability of target attainment (PTA) between IVP and intermittent infusion, defined as free cefepime concentrations above organism MIC for ≥ 70% of the time. Results At MICs of 0.25–0.5 mg/L, absolute differences in PTA were observed, with a reduction as great as 2.3% (89% to 86.7% for 30-minute intermittent infusion and IVP, respectively). At MICs of 1–4 mg/L, 30-minute intermittent infusion and IVP exhibited PTA differences as great as 5.4%, from 89.4% to 84%, respectively. At MICs of ≥8 mg/L, similar absolute differences existed; however, no regimen achieved a PTA >70%. Across renal function strata of 60, 100 and 140 mL/minute (within the same dosing group and MICs), better renal function lowered PTAs. Conclusions Simulations demonstrated that IVP cefepime resulted in lower PTAs than traditional intermittent infusion among a subset of elevated MICs. Clinicians should exercise caution in IVP strategy, as unintended clinical consequences are possible.

Published
2020

28. Early onset cerebral amyloid angiopathy following childhood exposure to cadaveric dura

Author

Mushtaq Wani, Sebastian Brandner, Gargi Banerjee, Henry Houlden, Zane Jaunmuktane, Matthew Adams, G. Alistair Lammie, Inder Sawhney, Ben Turner, David J. Werring, and Simon Mead

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Magnetic resonance imaging, medicine.disease, Hemangioma, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Neurology, Neuroimaging, mental disorders, medicine, Neurology (clinical), Cerebral amyloid angiopathy, Embolization, Age of onset, business, Cadaveric spasm, 030217 neurology & neurosurgery, Craniotomy
Abstract

Amyloid-β transmission has been described in patients both with and without iatrogenic Creutzfeldt-Jakob disease; however, there is little information regarding the clinical impact of this acquired amyloid-β pathology during life. Here, for the first time, we describe in detail the clinical and neuroimaging findings in 3 patients with early onset symptomatic amyloid-β cerebral amyloid angiopathy following childhood exposure to cadaveric dura (by neurosurgical grafting in 2 patients and tumor embolization in a third). Our observations provide further in vivo evidence that cerebral amyloid angiopathy might be caused by transmission of amyloid-β seeds (prions) present in cadaveric dura and have diagnostic relevance for younger patients presenting with suspected cerebral amyloid angiopathy. Ann Neurol 2019; 1-7 ANN NEUROL 2019;85:284-290.

Published
2019
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29. 110 Methylmalonic acid testing in neurological patients

Author

Katie Yoganathan, Ruth Ayling, Ben Turner, and Ruth Dobson

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract

Vitamin B12 deficiency can lead to neurological abnormalities including paraesthesia, ataxia and subacute combined degeneration of the cord (SACD). Nitrous oxide abuse leads to SACD via func- tional B12 deficiency. Methylmalonic acid (MMA) testing is increasingly available, but it remains unclear where MMA levels are clinically useful.We performed a quality improvement project examining Vitamin B12 and MMA levels in a cohort of neu- rological patients. All patients known to neurology who underwent same-day testing of B12 and MMA levels (2016–2019) were included.60 individual patient records were evaluated. 17 individuals (28%) had high MMA, of whom 6 individuals had SACD and 11 had peripheral neuropathy. These patients had B12 levels between 91–371ng/L (lower limit of normal (LLN) is 197ng/L). Of these, only one had severe B12 deficiency, 4 had moderate deficiency (150–197ng/L) and 12 (71%) had normal B12. The highest B12 level associated with raised MMA was 372ng/L. All individuals with B12 >372ng/L and neurological symptoms had normal MMA.In individuals with serum vitamin B12 above the lower 1/3 of the reference range and neurological symptoms/signs, MMA does not add to the clinical picture. Furthermore, MMA testing does not change management in patients with B12 levels below the LLN, all of whom should be treated for B12 deficiency. We suggest testing MMA in those with Vitamin B12 levels in the lower 1/3 of the reference range.katieyoganathan@gmail.com

Published
2022
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30. Personalised immunotherapy in active multiple sclerosis using injectable cladrib- ine: Follow-up of the BartsMS cohort

Author

Kimberley Allen-Philbey, Stefania De Trane, Ozlem Yildiz, Ashok Adams, Ben Turner, Monica Marta, Joela Mathews, Dan Altmann, Gavin Giovannoni, and Klaus Schmierer

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract

IntroductionCladribine tablets (Mavenclad®) are licensed for treating people with relapsing multiple sclerosis (pwRMS). We treated people with relapsing (pwRMS) and progressive MS (pwPMS) using sub- cutaneously administered cladribine (SCAC) since 2014. Here, we present up to five year follow-up on safety and efficacy.MethodsSCAC 10mg was given on 3–4 days during week 1. 0–3 doses were administered at week 5, according to week 4 lymphocyte count. A second cycle of SCAC was administered 11 months later. Follow-up included clinical outcome evaluation and pharmacovigilance. The proportion of pwMS with no evidence of (i) disease activity (NEDA) and (ii) progression or active disease (NEPAD) was calculated.Results211 pwMS received SCAC. 154/211 completed two treatment cycles. At baseline age was 44 (17–72) years, EDSS 1–8.5. Tolerability was good. One myocardial infarction and one breast cancer occurred. Two severely disabled pwMS died (one of influenza, one of encephalitis). Lymphopenia grade 3 was detected in ConclusionsSCAC was well tolerated. Frequency of significant lymphopenia was low. Efficacy in pwRMS corresponds with trial data. NEPAD rates in pwPMS were similar to licensed DMT.k.allen-philbey@nhs.net

Published
2022
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31. 213 Improving the investigation and management of papilloedema in an acute medical setting

Author

Catherine Hornby, Stephen Auger, Ben Jacobs, and Ben Turner

Subjects
Psychiatry and Mental health, Surgery, Neurology (clinical)
Abstract

AimTo streamline and improve the investigation of patients with papilloedema presenting to the acute medical take in a large teaching hospital.MethodsPatients seen on the acute medical take at the Royal London Hospital with suspected papil- loedema were identified retrospectively. A total of 19 patients were seen between April and November 2019. A number of modifiable delays to initial investigations and areas for improvement were identified from these data. A simple flowchart explaining key points in investigation and initial management of patients with papilloedema was devised and distributed to those involved in the acute take.ResultsThe identified areas for improvement included delays to lumbar puncture, failure to discuss management with neurologists after identification of raised intracranial pressure, and ensuring initial management was started in those with suspected idiopathic intracranial hypertension. There were also a number of instances in which papilloedema was not confirmed by an ophthalmologist prior to inap- propriate invasive investigations. Education and provision of better information to acute medics improved many of these outcomes.ConclusionA clear and easy to use flowchart for those involved in the acute take minimised errors identified and improved the initial investigation and management of papilloedema presenting to the acute medical take.catherine.hornby2@nhs.net

Published
2022
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32. Review: Claudio Celis Bueno, The Attention Economy: Labour, Time and Power in Cognitive Capitalism

Author

Ben Turner

Subjects
Power (social and political), Surplus value, Sociology and Political Science, 05 social sciences, 050602 political science & public administration, Economics, General Social Sciences, Attention economy, Context (language use), Cognition, Neoclassical economics, Capitalism, 0506 political science
Abstract

How should we conceptualise the turn to attention as a means of producing surplus value? Claudio Celis Bueno answers this question through a consideration of the attention economy in the context of a rethinking of Marxist political economy. Bueno accounts for the development of the economisation of attention through the concepts of value, labour and time, but also investigates how the shift to attention requires us to rethink the basis of these terms. Using the attention economy as an example, he develops a method of immanent critique which rejects a-historical understandings of labour, in order to show how the core concepts of Marxist political economy transform across different economic systems. Despite the clarity of this argument, Bueno opens an interesting but unanswered question as to how one transitions from this insight to a positive political project that may not be compatible with immanent critique.

Published
2018
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33. Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis

Author

Andrea Malaspina, Dominika Raciborska, Ben Turner, Richard W. Titball, Helen Morcrette, Sharmilee Gnanapavan, Michel R. Popoff, Richard Nicholas, N. Lewis, Sariqa Wagley, Monika Bokori-Brown, Caroline D’Arcy, College of Life and Environmental Sciences [Exeter], University of Exeter, Queen Mary University of London (QMUL), West London Neuroscience Centre [Charing Cross Hospital, London], Charing Cross Hospital & Imperial College, MS sciences limited, Bactéries anaérobies et Toxines, Institut Pasteur [Paris], Division of Brain Sciences [London], Imperial College London, Barts Health NHS Trust [London, UK], The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the MS Sciences Ltd and by the NIHR Exeter CRF., and Institut Pasteur [Paris] (IP)

Subjects
Multiple Sclerosis, Clostridium perfringens, [SDV]Life Sciences [q-bio], Bacterial Toxins, epsilon toxin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], CHO Cells, medicine.disease_cause, 03 medical and health sciences, Cricetulus, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Animals, Humans, 030212 general & internal medicine, Clinically isolated syndrome, biology, business.industry, Toxin, Multiple sclerosis, Clostridium perfringens epsilon toxin, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Molecular biology, 3. Good health, Blot, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Neurology, Pepscan, biology.protein, Neurology (clinical), Antibody, business, Original Research Papers, 030217 neurology & neurosurgery
Abstract

Background: It was recently reported that, using Western blotting, some multiple sclerosis (MS) patients in the United States had antibodies against epsilon toxin (Etx) from Clostridium perfringens, suggesting that the toxin may play a role in the disease. Objective: We investigated for serum antibodies against Etx in UK patients with clinically definite multiple sclerosis (CDMS) or presenting with clinically isolated syndrome (CIS) or optic neuritis (ON) and in age- and gender-matched controls. Methods: We tested sera from CDMS, CIS or ON patients or controls by Western blotting. We also tested CDMS sera for reactivity with linear overlapping peptides spanning the amino acid sequence (Pepscan) of Etx. Results: Using Western blotting, 24% of sera in the combined CDMS, CIS and ON groups ( n = 125) reacted with Etx. In the control group ( n = 125), 10% of the samples reacted. Using Pepscan, 33% of sera tested reacted with at least one peptide, whereas in the control group only 16% of sera reacted. Out of 61 samples, 21 (43%) were positive to one or other testing methodology. Three samples were positive by Western blotting and Pepscan. Conclusion: Our results broadly support the previous findings and the role of Etx in the aetiology of MS warrants further investigation.

Published
2018
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34. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

Ludwig Kappos, Amit Bar-Or, Bruce A C Cree, Robert J Fox, Gavin Giovannoni, Ralf Gold, Patrick Vermersch, Douglas L Arnold, Sophie Arnould, Tatiana Scherz, Christian Wolf, Erik Wallström, Frank Dahlke, Anat Achiron, Lutz Achtnichts, Kadriye Agan, Gulsen Akman-Demir, Alison B Allen, Jack P Antel, Alfredo Rodriguez Antiguedad, Michelle Apperson, Angela M Applebee, Guillermo Izquierdo Ayuso, Masayuki Baba, Ovidiu Bajenaru, Rodica Balasa, Belgin Petek Balci, Michael Barnett, Ann Bass, Veit U Becker, Mihaela Bejinariu, Florian Then Bergh, Arnfin Bergmann, Evanthia Bernitsas, Achim Berthele, Virender Bhan, Felix Bischof, Randall John Bjork, Gregg Blevins, Matthias Boehringer, Thomas Boerner, Robert Bonek, James D Bowen, Allen Bowling, Alexey N Boyko, Cavit Boz, Vera Bracknies, Stefan Braune, Vincenzo Brescia Morra, Bruno Brochet, Waldemar Brola, Paul Kenneth Brownstone, Miroslav Brozman, Donald Brunet, Ioan Buraga, Margaret Burnett, Mathias Buttmann, Helmut Butzkueven, Jonathan Cahill, Jonathan C Calkwood, William Camu, Mark Cascione, Giovani Castelnovo, Diego Centonze, Joao Cerqueira, Andrew Chan, Andrea Cimprichova, Stanley Cohan, Giancarlo Comi, Jill Conway, Joanna A Cooper, John Corboy, Jorge Correale, Brian Costell, David A Cottrell, Patricia K Coyle, Matthew Craner, Liying Cui, Luis Cunha, Anna Czlonkowska, Ana Martins da Silva, Joao de Sa, Jérôme de Seze, Marc Debouverie, Jan Debruyne, Danny Decoo, Gilles Defer, Tobias Derfuss, Norma H Deri, Bhupesh Dihenia, Peter Dioszeghy, Vladimir Donath, Benedicte Dubois, Martin Duddy, Pierre Duquette, Gilles Edan, Husnu Efendi, Stanton Elias, Peter J Emrich, Bonaventura Casanova Estruch, Evgeniy P Evdoshenko, Juergen Faiss, Alexander S Fedyanin, Wolfgang Feneberg, Jiske Fermont, Oscar Fernandez Fernandez, Francisco Coret Ferrer, Katharina Fink, Helen Ford, Corey Ford, Ada Francia, Mark Freedman, Benjamin Frishberg, Simonetta Galgani, George P Garmany, Klaus Gehring, Jeffrey Gitt, Claudio Gobbi, Lawrence P Goldstick, Rafael Arroyo Gonzalez, Francois Grandmaison, Nikolaos Grigoriadis, Olga Grigorova, Luigi Maria Edoardo Grimaldi, Jeffrey Gross, Katrin Gross-Paju, Mark Gudesblatt, Daniel Guillaume, Judith Haas, Viera Hancinova, Anca Hancu, Orla Hardiman, Arndt Harmjanz, Fedor R Heidenreich, G J D Hengstman, Joseph Herbert, Mark Herring, Suzanne Hodgkinson, Olaf M Hoffmann, Werner E Hofmann, William D Honeycutt, Le Hanh Hua, Dehui Huang, Yining Huang, DeRen Huang, Raymond Hupperts, Piroska Imre, Alan Keith Jacobs, Gabor Jakab, Elzbieta Jasinska, Kenichi Kaida, Jolanta Kalnina, Ara Kaprelyan, Guntis Karelis, Dimitrios Karussis, Amos Katz, Farit A Khabirov, Bhupendra Khatri, Takashi Kimura, Ilya Kister, Rasa Kizlaitiene, Eleonora Klimova, Juergen Koehler, Aparna Komatineni, Anselm Kornhuber, Krisztina Kovacs, Agnes Koves, Wojciech Kozubski, Georgi Krastev, Lauren B Krupp, Egon Kurca, Christoph Lassek, Guy Laureys, Liesly Lee, Eckart Lensch, Fritz Leutmezer, Hongzeng Li, Ralf A Linker, Michael Linnebank, Petra Liskova, Cristina Llanera, Jiahong Lu, Andreas Lutterotti, Jan Lycke, Richard Macdonell, Maciej Maciejowski, Mathias Maeurer, Rim V Magzhanov, Eva-Maria Maida, Lina Malciene, Yang Mao-Draayer, Girolama Alessandra Marfia, Clyde Markowitz, Vasileios Mastorodimos, Klotild Matyas, Jose Meca-Lallana, Juan Antonio Garcia Merino, Ioan Gheorghe Mihetiu, Ivan Milanov, Aaron E Miller, Andrejs Millers, Massimiliano Mirabella, Masanori Mizuno, Xavier Montalban, Lilina Montoya, Masahiro Mori, Stefanie Mueller, Jin Nakahara, Yuji Nakatsuji, Scott Newsome, Richard Nicholas, A Scott Nielsen, Esmaeil Nikfekr, Ugo Nocentini, Chiyoko Nohara, Kyoichi Nomura, Miroslav M Odinak, Tomas Olsson, B W van Oosten, Celia Oreja-Guevara, Patrick Oschmann, James Overell, Andrew Pachner, Gyula Panczel, Massimo Pandolfo, Caroline Papeix, Liliana Patrucco, Jean Pelletier, Raul Piedrabuena, Misha Pless, Udo Polzer, Krisztian Pozsegovits, Daiva Rastenyte, Sebastian Rauer, Gerd Reifschneider, Roberto Rey, Syed A Rizvi, Derrick Robertson, Jose Martinez Rodriguez, David Rog, Homayoun Roshanisefat, Vernon Rowe, Csilla Rozsa, Susan Rubin, Stanislaw Rusek, Francesco Saccà, Takahiko Saida, Antonio Vasco Salgado, Victoria Eugenia Fernandez Sanchez, Kalina Sanders, Maria Satori, Denis V Sazonov, Elio Angelo Scarpini, Eugen Schlegel, Myriam Schluep, Stephan Schmidt, Erich Scholz, H M Schrijver, Matthias Schwab, Raymond Schwartz, James Scott, Krzysztof Selmaj, Stuart Shafer, Basil Sharrack, Ivan A Shchukin, Yuko Shimizu, Penko Shotekov, Arno Siever, Karl-Otto Sigel, Scott Silliman, Magdolna Simo, Mihaela Simu, Vladimiro Sinay, Antonio Escartin Siquier, Aksel Siva, Ondrej Skoda, Andrew Solomon, Martin Stangel, Dusan Stefoski, Brian Steingo, Igor D Stolyarov, Pavel Stourac, Katrin Strassburger-Krogias, Erik Strauss, Olaf Stuve, Ivaylo Tarnev, Antonios Tavernarakis, Cristina Ramo Tello, Murat Terzi, Veronika Ticha, Marina Ticmeanu, Klaus Tiel-Wilck, Toomas Toomsoo, Niall Tubridy, Mark J Tullman, Hayrettin Tumani, Peter Turcani, Ben Turner, Antonio Uccelli, Francisco Javier Olascoaga Urtaza, Marta Vachova, Attila Valikovics, Silke Walter, Bart Van Wijmeersch, Ludo Vanopdenbosch, Joerg R Weber, Sara Weiss, Robert Weissert, Timothy West, Heinz Wiendl, Sandrine Wiertlewski, Brigitte Wildemann, Barbara Willekens, L H Visser, Galina Vorobeychik, Xianhao Xu, Takashi Yamamura, Yi N Yang, Sergio Martinez Yelamos, Michael Yeung, Alan Zacharias, Marvin Zelkowitz, Uwe Zettl, Meini Zhang, Hongyu Zhou, Ulf Zieman, Tjalf Ziemssen, Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital, University of Basel, Basel, Center for Neuroinflammation and Neurotherapeutics, and Multiple Sclerosis Division, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, Mellen Centre for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, Department of Neurology St. Josef-Hospital, Ruhr University Bochum, Germany, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Montreal Neurological Institute, McGill University, Montreal, QC, Canada, NeuroRx Research, Montreal, QC, Novartis Pharma AG, Lycalis, Brussels, AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., 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), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-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)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Kappos, Ludwig, Bar-Or, Amit, Cree, Bruce A C, Fox, Robert J, Giovannoni, Gavin, Gold, Ralf, Vermersch, Patrick, Arnold, Douglas L, Arnould, Sophie, Scherz, Tatiana, Wolf, Christian, Wallström, Erik, Dahlke, Frank, Achiron, Anat, Achtnichts, Lutz, Agan, Kadriye, Akman-Demir, Gulsen, Allen, Alison B, Antel, Jack P, Antiguedad, Alfredo Rodriguez, Apperson, Michelle, Applebee, Angela M, Ayuso, Guillermo Izquierdo, Baba, Masayuki, Bajenaru, Ovidiu, Balasa, Rodica, Balci, Belgin Petek, Barnett, Michael, Bass, Ann, Becker, Veit U, Bejinariu, Mihaela, Bergh, Florian Then, Bergmann, Arnfin, Bernitsas, Evanthia, Berthele, Achim, Bhan, Virender, Bischof, Felix, Bjork, Randall John, Blevins, Gregg, Boehringer, Matthia, Boerner, Thoma, Bonek, Robert, Bowen, James D, Bowling, Allen, Boyko, Alexey N, Boz, Cavit, Bracknies, Vera, Braune, Stefan, Brescia Morra, Vincenzo, Brochet, Bruno, Brola, Waldemar, Brownstone, Paul Kenneth, Brozman, Miroslav, Brunet, Donald, Buraga, Ioan, Burnett, Margaret, Buttmann, Mathia, Butzkueven, Helmut, Cahill, Jonathan, Calkwood, Jonathan C, Camu, William, Cascione, Mark, Castelnovo, Giovani, Centonze, Diego, Cerqueira, Joao, Chan, Andrew, Cimprichova, Andrea, Cohan, Stanley, Comi, Giancarlo, Conway, Jill, Cooper, Joanna A, Corboy, John, Correale, Jorge, Costell, Brian, Cottrell, David A, Coyle, Patricia K, Craner, Matthew, Cui, Liying, Cunha, Lui, Czlonkowska, Anna, da Silva, Ana Martin, de Sa, Joao, de Seze, Jérôme, Debouverie, Marc, Debruyne, Jan, Decoo, Danny, Defer, Gille, Derfuss, Tobia, Deri, Norma H, Dihenia, Bhupesh, Dioszeghy, Peter, Donath, Vladimir, Dubois, Benedicte, Duddy, Martin, Duquette, Pierre, Edan, Gille, Efendi, Husnu, Elias, Stanton, Emrich, Peter J, Estruch, Bonaventura Casanova, Evdoshenko, Evgeniy P, Faiss, Juergen, Fedyanin, Alexander S, Feneberg, Wolfgang, Fermont, Jiske, Fernandez, Oscar Fernandez, Ferrer, Francisco Coret, Fink, Katharina, Ford, Helen, Ford, Corey, Francia, Ada, Freedman, Mark, Frishberg, Benjamin, Galgani, Simonetta, Garmany, George P, Gehring, Klau, Gitt, Jeffrey, Gobbi, Claudio, Goldstick, Lawrence P, Gonzalez, Rafael Arroyo, Grandmaison, Francoi, Grigoriadis, Nikolao, Grigorova, Olga, Grimaldi, Luigi Maria Edoardo, Gross, Jeffrey, Gross-Paju, Katrin, Gudesblatt, Mark, Guillaume, Daniel, Haas, Judith, Hancinova, Viera, Hancu, Anca, Hardiman, Orla, Harmjanz, Arndt, Heidenreich, Fedor R, Hengstman, G J D, Herbert, Joseph, Herring, Mark, Hodgkinson, Suzanne, Hoffmann, Olaf M, Hofmann, Werner E, Honeycutt, William D, Hua, Le Hanh, Huang, Dehui, Huang, Yining, Huang, Deren, Hupperts, Raymond, Imre, Piroska, Jacobs, Alan Keith, Jakab, Gabor, Jasinska, Elzbieta, Kaida, Kenichi, Kalnina, Jolanta, Kaprelyan, Ara, Karelis, Gunti, Karussis, Dimitrio, Katz, Amo, Khabirov, Farit A, Khatri, Bhupendra, Kimura, Takashi, Kister, Ilya, Kizlaitiene, Rasa, Klimova, Eleonora, Koehler, Juergen, Komatineni, Aparna, Kornhuber, Anselm, Kovacs, Krisztina, Koves, Agne, Kozubski, Wojciech, Krastev, Georgi, Krupp, Lauren B, Kurca, Egon, Lassek, Christoph, Laureys, Guy, Lee, Liesly, Lensch, Eckart, Leutmezer, Fritz, Li, Hongzeng, Linker, Ralf A, Linnebank, Michael, Liskova, Petra, Llanera, Cristina, Lu, Jiahong, Lutterotti, Andrea, Lycke, Jan, Macdonell, Richard, Maciejowski, Maciej, Maeurer, Mathia, Magzhanov, Rim V, Maida, Eva-Maria, Malciene, Lina, Mao-Draayer, Yang, Marfia, Girolama Alessandra, Markowitz, Clyde, Mastorodimos, Vasileio, Matyas, Klotild, Meca-Lallana, Jose, Merino, Juan Antonio Garcia, Mihetiu, Ioan Gheorghe, Milanov, Ivan, Miller, Aaron E, Millers, Andrej, Mirabella, Massimiliano, Mizuno, Masanori, Montalban, Xavier, Montoya, Lilina, Mori, Masahiro, Mueller, Stefanie, Nakahara, Jin, Nakatsuji, Yuji, Newsome, Scott, Nicholas, Richard, Nielsen, A Scott, Nikfekr, Esmaeil, Nocentini, Ugo, Nohara, Chiyoko, Nomura, Kyoichi, Odinak, Miroslav M, Olsson, Toma, van Oosten, B W, Oreja-Guevara, Celia, Oschmann, Patrick, Overell, Jame, Pachner, Andrew, Panczel, Gyula, Pandolfo, Massimo, Papeix, Caroline, Patrucco, Liliana, Pelletier, Jean, Piedrabuena, Raul, Pless, Misha, Polzer, Udo, Pozsegovits, Krisztian, Rastenyte, Daiva, Rauer, Sebastian, Reifschneider, Gerd, Rey, Roberto, Rizvi, Syed A, Robertson, Derrick, Rodriguez, Jose Martinez, Rog, David, Roshanisefat, Homayoun, Rowe, Vernon, Rozsa, Csilla, Rubin, Susan, Rusek, Stanislaw, Saccà, Francesco, Saida, Takahiko, Salgado, Antonio Vasco, Sanchez, Victoria Eugenia Fernandez, Sanders, Kalina, Satori, Maria, Sazonov, Denis V, Scarpini, Elio Angelo, Schlegel, Eugen, Schluep, Myriam, Schmidt, Stephan, Scholz, Erich, Schrijver, H M, Schwab, Matthia, Schwartz, Raymond, Scott, Jame, Selmaj, Krzysztof, Shafer, Stuart, Sharrack, Basil, Shchukin, Ivan A, Shimizu, Yuko, Shotekov, Penko, Siever, Arno, Sigel, Karl-Otto, Silliman, Scott, Simo, Magdolna, Simu, Mihaela, Sinay, Vladimiro, Siquier, Antonio Escartin, Siva, Aksel, Skoda, Ondrej, Solomon, Andrew, Stangel, Martin, Stefoski, Dusan, Steingo, Brian, Stolyarov, Igor D, Stourac, Pavel, Strassburger-Krogias, Katrin, Strauss, Erik, Stuve, Olaf, Tarnev, Ivaylo, Tavernarakis, Antonio, Tello, Cristina Ramo, Terzi, Murat, Ticha, Veronika, Ticmeanu, Marina, Tiel-Wilck, Klau, Toomsoo, Tooma, Tubridy, Niall, Tullman, Mark J, Tumani, Hayrettin, Turcani, Peter, Turner, Ben, Uccelli, Antonio, Urtaza, Francisco Javier Olascoaga, Vachova, Marta, Valikovics, Attila, Walter, Silke, Van Wijmeersch, Bart, Vanopdenbosch, Ludo, Weber, Joerg R, Weiss, Sara, Weissert, Robert, West, Timothy, Wiendl, Heinz, Wiertlewski, Sandrine, Wildemann, Brigitte, Willekens, Barbara, Visser, L H, Vorobeychik, Galina, Xu, Xianhao, Yamamura, Takashi, Yang, Yi N, Yelamos, Sergio Martinez, Yeung, Michael, Zacharias, Alan, Zelkowitz, Marvin, Zettl, Uwe, Zhang, Meini, Zhou, Hongyu, Zieman, Ulf, Ziemssen, Tjalf, and EXPAND Clinical Investigators

Subjects
Adult, Male, 0301 basic medicine, Relative risk reduction, medicine.medical_specialty, Adolescent, Placebo, law.invention, Cohort Studies, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Chronic Progressive / drug therapy, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Benzyl Compounds, Clinical endpoint, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, Expanded Disability Status Scale, Dose-Response Relationship, Drug, business.industry, Hazard ratio, General Medicine, Middle Aged, Multiple Sclerosis, Chronic Progressive, Fingolimod, Treatment Outcome, Settore M-EDF/01 - METODI E DIDATTICHE DELLE ATTIVITÀ MOTORIE, 030104 developmental biology, Siponimod, chemistry, Disease Progression, Azetidines, Female, Settore MED/26 - Neurologia, Human medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, medicine.drug
Abstract

Summary Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding Novartis Pharma AG.

Published
2018
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35. The limits of culture in political theory: A critique of multiculturalism from the perspective of anthropology’s ontological turn

Author

Ben Turner

Subjects
Sociology and Political Science, Anthropology, media_common.quotation_subject, 05 social sciences, Perspective (graphical), 06 humanities and the arts, 0603 philosophy, ethics and religion, 0506 political science, Critical discussion, Politics, Multiculturalism, 060302 philosophy, Political Science and International Relations, 050602 political science & public administration, Political philosophy, Sociology, media_common
Abstract

Political theorists have developed and refined the concept of culture through much critical discussion with anthropology. This article will deepen this engagement by claiming that political theory has glossed over a crucial aspect of the role of the concept of culture, rather than defined it incorrectly. It will be argued that culture represents one way of accounting for the variety of human groups by drawing on the recent ‘ontological turn’ in anthropology. This rests on an understanding of ontology as a system of classifying entities anterior to social relations rather than a philosophical position. The article will argue against culture’s status as a neutral and universal method of understanding human diversity by situating it within a pluralist approach to ontology, that posits multiple ontological schemas which form different social systems, each with their own understanding of human difference. Through an investigation of the implicit ontological commitments of multiculturalism it will be claimed that all political positions rest on a set of ontological presuppositions, and that these classifications place restrictions on the politics that they can express. Thus, political theorists should be vigilant of implicit ontological biases, represented here by culture, if they are to positively accommodate human difference.

Published
2018
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36. Archaeosine Modification of Archaeal tRNA: Role in Structural Stabilization

Author

Dirk Iwata-Reuyl, Katrin Weidenbach, Ruth A. Schmitz, Kenneth M. Stedman, Brett W. Burkhart, Ben Turner, Valérie de Crécy-Lagard, Patrick A. Limbach, Thomas J. Santangelo, and Robert L. Ross

Subjects
TRNA modification, RNA Stability, TRNA processing, Context (language use), RNA, Archaeal, 01 natural sciences, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, RNA, Transfer, Molecular Biology, 030304 developmental biology, 0303 health sciences, Guanosine, biology, 010405 organic chemistry, biology.organism_classification, 0104 chemical sciences, Thermococcus kodakarensis, Thermococcus, A-site, Biochemistry, chemistry, Methanosarcina, Transfer RNA, Dihydrouridine, Research Article
Abstract

Archaeosine (G(+)) is a structurally complex modified nucleoside found quasi-universally in the tRNA of Archaea and located at position 15 in the dihydrouridine loop, a site not modified in any tRNA outside the Archaea. G(+) is characterized by an unusual 7-deazaguanosine core structure with a formamidine group at the 7-position. The location of G(+) at position 15, coupled with its novel molecular structure, led to a hypothesis that G(+) stabilizes tRNA tertiary structure through several distinct mechanisms. To test whether G(+) contributes to tRNA stability and define the biological role of G(+), we investigated the consequences of introducing targeted mutations that disrupt the biosynthesis of G(+) into the genome of the hyperthermophilic archaeon Thermococcus kodakarensis and the mesophilic archaeon Methanosarcina mazei, resulting in modification of the tRNA with the G(+) precursor 7-cyano-7-deazaguansine (preQ(0)) (deletion of arcS) or no modification at position 15 (deletion of tgtA). Assays of tRNA stability from in vitro-prepared and enzymatically modified tRNA transcripts, as well as tRNA isolated from the T. kodakarensis mutant strains, demonstrate that G(+) at position 15 imparts stability to tRNAs that varies depending on the overall modification state of the tRNA and the concentration of magnesium chloride and that when absent results in profound deficiencies in the thermophily of T. kodakarensis. IMPORTANCE Archaeosine is ubiquitous in archaeal tRNA, where it is located at position 15. Based on its molecular structure, it was proposed to stabilize tRNA, and we show that loss of archaeosine in Thermococcus kodakarensis results in a strong temperature-sensitive phenotype, while there is no detectable phenotype when it is lost in Methanosarcina mazei. Measurements of tRNA stability show that archaeosine stabilizes the tRNA structure but that this effect is much greater when it is present in otherwise unmodified tRNA transcripts than in the context of fully modified tRNA, suggesting that it may be especially important during the early stages of tRNA processing and maturation in thermophiles. Our results demonstrate how small changes in the stability of structural RNAs can be manifested in significant biological-fitness changes.

Published
2020
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37. Politicising the Epokhé: Bernard Stiegler and the Politics of Epochal Suspension

Author

Ben Turner and Apostolescu, Iulian

Subjects
media_common.quotation_subject, Philosophy, JC, Temporality, Epistemology, Politics, Framing (social sciences), Social system, Pharmakon, Transcendental number, Consciousness, Internal time, B1, media_common
Abstract

For Husserl, the phenomenological epoche is primarily methodological, allowing access to the structures of transcendental consciousness by way of suspending worldly influence. This chapter will demonstrate how this methodological principle is rethought as political in the work of Bernard Stiegler. For Stiegler the epokhe is both the suspension of existing social systems, and a moment of critical redoubling, where the source of disruption is integrated into a new ‘epoch’. In particular it will be shown how Stiegler develops this double understanding of the epokhe through his reading of retentionality as found in the lectures On the Consciousness of Internal Time to develop an understanding of the epochal framing of temporality by technics. By drawing connections between this version of retentionality and the pharmacological character of technics, as simultaneously poisonous and curative, the political stakes of the epokhe lie in the need to fight the poisonous aspects of epochal suspension.

Published
2019

38. Ideology and Post-structuralism after Bernard Stiegler

Author

Ben Turner

Subjects
Stupidity, media_common.quotation_subject, 05 social sciences, Geography, Planning and Development, JC, Post structuralism, Object (philosophy), 0506 political science, Epistemology, 050903 gender studies, Political Science and International Relations, 050602 political science & public administration, Ideology, Sociology, 0509 other social sciences, Social science, B1, media_common
Abstract

What is the objective of ideology critique today? A unique answer to this question can be found in the work of Bernard Stiegler: the object of ideology critique is stupidity. Stiegler’s work will be situated with regard to the study of ideology and post-structuralism, reframed as respective versions of a dichotomy between critical and neutral theories, to show how Stiegler’s conception of ideology encompasses both. How he thinks ideology 'after' post-structuralism will be explored through his reading of Deleuze and Guattari. First, by seeing how Stiegler capitalises upon the theoretical developments of Deleuze and Guattari to rethink the notion of ideology. Second, by seeing how this understanding of ideology is folded back on their work, in order to discern how post-structuralism can be critiqued by a theory of ideology that utilises its views. From the perspective of his reading of desire in Deleuze, Guattari, and Freud, Stiegler shows how ideology destroys the desire to rethink ideas, and enforces stupidity. Third, after Stiegler’s theoretical labour, we arrive at a notion of ideology dichotomised between the critical and the stupid, tasking critique with the invention of new forms of desire, and the struggle against stupidity.

Published
2016
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39. Science and Ideology Revisited: Necessity, Contingency and the Critique of Ideologies in Meillassoux and Malabou

Author

Ben Turner

Abstract

Political thought influenced by post-structuralism rarely invokes ideology critique as a meaningful category of analysis, criticizing the structuralist attribution of contingency and necessity to, respectively, ideology and science. This article will challenge this position utilising recent philosophical considerations of necessity and contingency that rehabilitate ideology critique. Drawing on scientific materials, both Quentin Meillassoux and Catherine Malabou develop a form of necessity inhabited by contingency. It will be argued that this work allows a reconsideration of the usefulness of science for ideology critique in a manner that doesn't rely on an attribution of scientific necessity to the politics of the critic.

Published
2018

40. Affinity and Antagonism: Structuralism, Comparison and Transformation in Pluralist Political Ontology

Author

Ben Turner

Subjects
Sociology and Political Science, 05 social sciences, 050601 international relations, 0506 political science, Epistemology, Philosophy, Politics, Transformation (function), Pluralism (political theory), Structuralism (philosophy of mathematics), 050602 political science & public administration, Ontology, Sociology
Abstract

This article develops a comparative and recursive approach to political ontology by drawing on the ontological turn in anthropology. It claims that if ontological commitments define reality, then the use of ontology by recent pluralist political theorists must undercut pluralism. By charting contemporary anthropology’s rereading of structuralism as part of a plural understanding of ontology, it will be shown that any political ontology places limits on the political, and thus cannot exhaust political experience. This position will be established through an analysis of the role of Claude Lévi-Strauss in the work of Ernesto Laclau and Chantal Mouffe and a comparison with the political ontology represented by perspectivism and potential affinity. Anthropology’s lesson for political theory is that ontology cannot simply be revised and treated in the singular, but that political ontologies must be analysed comparatively to reveal the shortcomings of, and recursively alter, one’s own political frame of reference.

Published
2018

41. Early onset cerebral amyloid angiopathy following childhood exposure to cadaveric dura

Author

Gargi, Banerjee, Matthew E, Adams, Zane, Jaunmuktane, G, Alistair Lammie, Ben, Turner, Mushtaq, Wani, Inder M S, Sawhney, Henry, Houlden, Simon, Mead, Sebastian, Brandner, and David J, Werring

Subjects
Adult, Male, Hemangioma, Cavernous, Central Nervous System, Amyloid beta-Peptides, Skull Fractures, Iatrogenic Disease, Middle Aged, Brief Communication, Embolization, Therapeutic, Magnetic Resonance Imaging, Parotid Neoplasms, Cerebral Amyloid Angiopathy, Cancer Survivors, mental disorders, Cadaver, Humans, Female, Papilloma, Choroid Plexus, Dura Mater, Age of Onset, Brief Communications, Craniotomy
Abstract

Amyloid‐β transmission has been described in patients both with and without iatrogenic Creutzfeldt–Jakob disease; however, there is little information regarding the clinical impact of this acquired amyloid‐β pathology during life. Here, for the first time, we describe in detail the clinical and neuroimaging findings in 3 patients with early onset symptomatic amyloid‐β cerebral amyloid angiopathy following childhood exposure to cadaveric dura (by neurosurgical grafting in 2 patients and tumor embolization in a third). Our observations provide further in vivo evidence that cerebral amyloid angiopathy might be caused by transmission of amyloid‐β seeds (prions) present in cadaveric dura and have diagnostic relevance for younger patients presenting with suspected cerebral amyloid angiopathy. Ann Neurol 2019; 1–7 ANN NEUROL 2019;85:284–290.

Published
2018

42. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND)

Author

Raju Kapoor, Pei-Ran Ho, Nolan Campbell, Ih Chang, Aaron Deykin, Fiona Forrestal, Nisha Lucas, Bei Yu, Douglas L Arnold, Mark S Freedman, Myla D Goldman, Hans-Peter Hartung, Eva Kubala Havrdová, Douglas Jeffery, Aaron Miller, Finn Sellebjerg, Diego Cadavid, Dan Mikol, Deborah Steiner, Emmanuel Bartholomé, Marie D'Hooghe, Massimo Pandolfo, Bart Van Wijmeersch, Virender Bhan, Gregg Blevins, Donald Brunet, Virginia Devonshire, Pierre Duquette, Mark Freedman, François Grand'Maison, François Jacques, Yves Lapierre, Liesly Lee, Sarah Morrow, Michael Yeung, Michal Dufek, Petr Kanovsky, Ivana Stetkarova, Marika Talabova, Jette Frederiksen, Matthias Kant, Thor Petersen, Mads Ravnborg, Laura Airas, Irina Elovaara, Juha-Pekka Eralinna, Taneli Sarasoja, Abdullatif Al Khedr, David Brassat, Bruno Brochet, William Camu, Marc Debouverie, David Laplaud, Christine Lebrun Frenay, Jean Pelletier, Patrick Vermersch, Sandra Vukusi, Karl Baum, Achim Berthele, Juergen Faiss, Peter Flachenecker, Reinhard Hohlfeld, Markus Krumbholz, Christoph Lassek, Mathias Maeurer, Sven Meuth, Tjalf Ziemssen, Orla Hardiman, Christopher McGuigan, Anat Achiron, Dimitrios Karussis, Roberto Bergamaschi, Vincenzo Brescia Morra, Giancarlo Comi, Salvatore Cottone, Luigi Grimaldi, Giovanni Luigi Mancardi, Luca Massacesi, Ugo Nocentini, Marco Salvetti, Elio Scarpini, Patrizia Sola, Gioacchino Tedeschi, Maria Trojano, Mauro Zaffaroni, Stephan Frequin, Raymond Hupperts, Joep Killestein, Hans Schrijver, Ronald Van Dijl, Erik van Munster, Maciej Czarnecki, Wieslaw Drozdowski, Waldemar Fryze, Hanka Hertmanowska, Jan Ilkowski, Anna Kaminska, Gabriela Klodowska-Duda, Maciej Maciejowski, Ewa Motta, Ryszard Podemski, Andrzej Potemkowski, Teresa Rog, Krzysztof Selmaj, Zbigniew Stelmasiak, Adam Stepien, Andrzej Tutaj, Jacek Zaborski, Alexey Boyko, Zanna Chefranova, Evgeny Evdoshenko, Farit Khabirov, Stella Sivertseva, Eduard Yakupov, Jose Carlos Alvarez Cermeño, Antonio Escartin, Oscar Fernandez Fernandez, Antonio Garcia-Merino, Miguel Angel Hernandez Perez, Guillermo Izquierdo Ayuso, José Meca Lallana, Xavier Montalban Gairin, Celia Oreja-Guevara, Albert Saiz Hinarejos, Martin Gunnarsson, Jan Lycke, Claes Martin, Fredrik Piehl, Homayoun Roshanisefat, Peter Sundstrom, Martin Duddy, Bruno Gran, Timothy Harrower, Jeremy Hobart, Martin Lee, Paul Mattison, Richard Nicholas, Owen Pearson, Waqar Rashid, David Rog, Basil Sharrack, Eli Silber, Ben Turner, Anna Williams, John Woolmore, Carolyn Young, Daniel Bandari, Joseph Berger, Ann Camac, Stanley Cohan, Jill Conway, Keith Edwards, Michelle Fabian, Jack Florin, Steven Freedman, Dennis Garwacki, Myla Goldman, Daniel Harrison, Craig Herrman, Deren Huang, Adil Javed, Stephen Kamin, George Katsamakis, Bhupendra Khatri, Annette Langer-Gould, Sharon Lynch, David Mattson, Tamara Miller, Augusto Miravalle, Harold Moses, Suraj Muley, James Napier, Allen Nielsen, Andrew Pachner, Gabriel Pardo, MaryAnn Picone, Derrick Robertson, Walter Royal, Christopher Sheppard, Ben Thrower, Cary Twyman, Emmanuelle Waubant, Jeanette Wendt, Vijayshree Yadav, Rana Zabad, Greg Zarelli, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, University College London Hospitals NHS Foundation Trust [London, UK] (UCLH), Biogen Inc. [Cambridge, MA, USA], Montreal Neurological Institute, Montreal, QC, Canada, NeuroRx Research, Montreal, QC, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, University of Virginia, Charlottesville, VA, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], First Faculty of Medicine-Charles University in Prague and General University Hospital in Prague, Piedmont HealthCare, Mooresville, NC, Icahn School of Medicine at Mount Sinai, New York, NY, University of Copenhagen = Københavns Universitet (UCPH), AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., 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), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Outcome Assessment, secondary progressive multiple sclerosis, natalizumab, Placebo-controlled study, multicenter, Severity of Illness Index, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Natalizumab, Randomized controlled trial, law, Outcome Assessment, Health Care, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Progressive multifocal leukoencephalopathy, Multiple Sclerosis, Chronic Progressive, Middle Aged, Chronic Progressive, Research Design, Disease Progression, Female, Settore MED/26 - Neurologia, medicine.drug, Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Population, Clinical Neurology, Double-Blind Method, Hand, Humans, Immunologic Factors, Young Adult, interferon beta 1b, 03 medical and health sciences, Internal medicine, medicine, education, Expanded Disability Status Scale, business.industry, Multiple sclerosis, ms, medicine.disease, Health Care, 030104 developmental biology, Siponimod, chemistry, brain atrophy, Neurology (clinical), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

BACKGROUND: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses.METHODS: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18-58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0-6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0-5·5 vs 6·0-6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181.FINDINGS: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66-1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74-1·53; nominal p=0·753) or the T25FW (0·98, 0·74-1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40-0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108-221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred.INTERPRETATION: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components.FUNDING: Biogen.

Published
2018
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43. Lateral Velocity Variations in the Darai Limestone, Papua New Guinea Foreland

Author

Ben Turner and Andrew Nelson

Subjects
Paleontology, Lateral velocity, parasitic diseases, General Engineering, New guinea, Drilling, Geophysics, Structural basin, Foreland basin, geographic locations, Geology
Abstract

A combination of exploration and appraisal drilling results from wells on three adjacent discoveries in the Papuan Basin, western Papua New Guinea foreland, shows significant lateral velocity varia...

Published
2015
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45. Hope: A further dimension for engaging family members of people with ABI

Author

Melissa Kendall, Ben Turner, Pim Kuipers, Jennifer Fleming, Emmah Doig, and Marion Mitchell

Subjects
Adult, Male, False hope, medicine.medical_treatment, Emotions, Physical Therapy, Sports Therapy and Rehabilitation, Community integration, Peer support, Cohort Studies, Hope, Young Adult, Nursing, Humans, Medicine, Family, Dimension (data warehouse), Acquired brain injury, Retrospective Studies, Inpatients, Rehabilitation, Social work, business.industry, Social Support, Inpatient setting, Middle Aged, medicine.disease, Treatment Outcome, Brain Injuries, Female, Neurology (clinical), business
Abstract

OBJECTIVE: To explore the experiences of patients and family members about their involvement in brain injury rehabilitation.METHODS: This study comprised individual and group interviews with 14 ex-patients and family members. Interviews explored effects of inpatient rehabilitation on family relationships. Interview audio recordings were analysed using an interpretive approach by two independent researchers. RESULTS: Findings clearly confirmed the significance of engaging family members in inpatient rehabilitation, and specifically reinforced the importance of informational, emotional, practical and peer support. However, the key finding of the study was the importance of hope, and the need for rehabilitation professionals to foster hope. Despite not having included any questions on this topic, all interviewees noted the importance of hope, some saw it as fundamental to positive outcomes, and many were unconvinced of rehabilitation professionals' concern to avoid false hope. Various dimensions of hope are explored.CONCLUSIONS: The study notes that hope has been identified as highly important in many areas beyond brain injury rehabilitation. Based on this small preliminary study, the issue of hope is seen as a key focus for future research.BACKGROUND: Family member engagement is increasingly recognised as an influential factor in the rehabilitation continuum following Acquired Brain Injury, including the inpatient setting and longer-term community integration phases.

Published
2014
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46. 212 Is there an ethnicity bias of access to MS services? The barts health experience revisited

Author

Klaus Schmierer, Ben Turner, Gavin Giovannoni, Kimberley Allen-Philbey, and Facundo Silveira

Subjects
medicine.medical_specialty, South asia, business.industry, Ethnic group, Retrospective cohort study, Audit, Disease, Psychiatry and Mental health, Service experience, Family medicine, East london, Medicine, Surgery, Neurology (clinical), business, Inclusion (education)
Abstract

IntroductionPrinciple 1 of the NHS constitution states that access to services should be non-discriminatory including ethnic background. Early diagnosis and initiation of disease modifying treatment (DMT) in people with multiple sclerosis (pwMS) is important for prognosis. We report findings from a re-audit of ethnic equity of clinical service experience in pwMS in east London.MethodsRetrospective cohort of pwMS ≥18 years old, diagnosed between 2014–2017 with 2 years of follow-up, attending Neurology services at Barts Health NHS Trust. We compared access to MS services between ethnic groups. Result variables included (i) first symptom to diagnosis (S2D) and (ii) diagnosis to DMT (D2T).Results59 pwMS fulfilled inclusion criteria, 7/59 were Black, 13/59 South Asian, 22/59 White and 17/59 as Other. There was a non-significant trend towards shorter S2D in White pwMS (1.2 years) compared to the other groups (Black 1.94, South Asian 1.93 and Other 1.55) (p=0.54). No difference was observed regarding D2T (Black 0.51 years, South Asian 0.31, White 0.58 and Other 0.47, p=0.25).ConclusionReassuringly, no ethnic inequity of access to MS services was detected, confirming findings of the original audit.

Published
2019
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47. 192 Does socioeconomic status impact on the prescription of disease-modifying treatments in people with multiple sclerosis?

Author

Sharmilee Gnanapavan, Özlem Yildiz, Ben Turner, Monica Marta, Kimberley Allen-Philbey, Joela Mathews, Gavin Giovannoni, Sebastian Suarez, Klaus Schmierer, and Saúl Reyes

Subjects
medicine.medical_specialty, business.industry, Disease, Fingolimod, Psychiatry and Mental health, Natalizumab, Internal medicine, medicine, Alemtuzumab, Surgery, Neurology (clinical), Glatiramer acetate, Medical prescription, business, Socioeconomic status, Patient education, medicine.drug
Abstract

ObjectiveTo examine the association between socioeconomic status (SES) and prescription of disease-modifying treatments (DMTs) in people with multiple sclerosis (pwMS).MethodsA cross-sectional study was conducted among 734 pwMS aged ≥18 years attending the neuroinflammation service at The Royal London Hospital (Barts Health NHS Trust) between 1997 and 2017. SES was determined by patient income and education extracted from the English Index of Multiple Deprivation. Multinomial logistic regression was performed to assess differences between SES and prescription of DMTs.ResultsDMTs were categorized as follows: moderate efficacy therapies included Glatiramer Acetate and Beta-Interferons (n=81, 11.04%), high efficacy therapies included Cladribine, Fingolimod and Dimethyl Fumarate (n=409, 55.72%), and very-high efficacy therapies included Natalizumab and Alemtuzumab (n=244, 33.24%). Medians for income and education deciles were 4 (IQR 3–7) and 6 (IQR 4–8), respectively. Patient income was not associated with increased odds of being prescribed high efficacy (OR, 1.02; 95% CI, 0.91–1.14; p=0.814) or very-high efficacy DMTs (OR, 1.01; 95% CI, 0.90–1.14; p=0.732). Similarly, patient education was not associated with the prescription of high efficacy (OR, 0.96; 95% CI, 0.84–1.10; p=0.585) or very-high efficacy DMTs (OR, 0.96; 95% CI, 0.84–1.10; p=0.538).ConclusionsSES was not predictive of prescription of DMTs in this single-centre study. It would be of interest to compare our data with other MS services, and to map these results onto the inequity in access to DMTs across the UK.

Published
2019
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