Protocol for The Toxin Study: Understanding clinical and patient reported response of children and young people with cerebral palsy to intramuscular lower limb Botulinum neurotoxin-A injections, exploring all domains of the ICF. A pragmatic longitudinal observational study using a prospective one-group repeated measures design

INTRODUCTION: Botulinum neurotoxin-A (BoNT-A) is an accepted treatment modality for the management of hypertonia in children and young people with cerebral palsy (CYPwCP). Nevertheless, there are concerns about the long-term effects of BoNT-A, with a lack of consensus regarding the most meaningful outcome measures to guide its use. Most evidence to date is based on short-term outcomes, related to changes at impairment level (restrictions of body functions and structures), rather than changes in adaptive skills (enabling both activity and participation). The proposed study aims to evaluate clinical and patient reported outcomes in ambulant CYPwCP receiving lower limb BoNT-A injections over a 12-month period within all domains of the WHO's International Classification of Functioning, Disability and Health and health-related quality of life (HRQoL). METHODS AND ANALYSIS: This pragmatic prospective longitudinal observational study will use a one-group repeated measures design. Sixty CYPwCP, classified as Gross Motor Function Classification System (GMFCS) levels I-III, aged between 4 and 18 years, will be recruited from an established movement disorder service in London, UK. Standardised clinical and patient reported outcome measures within all ICF domains; body structures and function, activity (including quality of movement), goal attainment, participation and HRQoL, will be collected preinjection and at 6 weeks, 6 months and up to 12 months postinjection. A representative subgroup of children and carers will participate in a qualitative component of the study, exploring how their experience of BoNT-A treatment relates to clinical outcome measures. ETHICS AND DISSEMINATION: Central London Research Ethics Committee has granted ethics approval (#IRAS 211617 #REC 17/LO/0579). Findings will be disseminated in peer-reviewed publications, conferences and via networks to participants and relevant stakeholders using a variety of accessible formats including social media

Rebuilding the workplace to promote young workers' mental health

Purpose Young adults have been particularly adversely affected by COVID-19-related disruptions, especially in relation to industries with an over-representation of young adults. This study, a report, aims to discuss the findings from survey data from young adults who reported poorer mental health comparative to older generations prior to the pandemic. Drawing on the international literature and the research findings, the authors propose recommendations for rebuilding the workplace post-pandemic to support young adult's mental health. Design/methodology/approach Data from 1,999 respondents from 200 organisations in the UK were sought in relation to workplace well-being and mental health through a 15-item multiple choice online survey. Overall, 17% of the sample were senior management, 31% junior management, 37% in non-management roles and a further 15% stated “other”. Exploratory quantitative analyses were undertaken to assess differences in responses to questions between age groups. Findings Participants in the 16–25-year-old age group were more likely than any other age group to report that work adversely affected their mental health, that their mental health challenges influenced their performance at work, that they had witnessed colleagues' employment negatively influenced by mental health challenges and they felt more comfortable citing physical health challenges for absence than mental health difficulties. Originality/value COVID-19-related disruptions meant a large-scale move to remote working for many people. As we return to physical workplaces, we have an exciting opportunity to reform and improve the status quo. The findings, in relation to the mental health of young adults, highlight key risk factors that need to be addressed. Keyword

The Association of Cusp-Aligned Arcs With Plasma in the Magnetotail Implies a Closed Magnetosphere

We investigate a 15-day period in October 2011. Auroral observations by the Special Sensor Ultraviolet Spectrographic Imager instrument onboard the Defense Meteorological Satellite Program F16, F17, and F18 spacecraft indicate that the polar regions were covered by weak cusp-aligned arc (CAA) emissions whenever the interplanetary magnetic field (IMF) clock angle was small, |θ| < 45°, which amounted to 30% of the time. Simultaneous observations of ions and electrons in the tail by the Cluster C4 and Geotail spacecraft showed that during these intervals dense (≈1 cm−3) plasma was observed, even as far from the equatorial plane of the tail as |ZGSE| ≈ 13 RE. The ions had a pitch angle distribution peaking parallel and antiparallel to the magnetic field and the electrons had pitch angles that peaked perpendicular to the field. We interpret the counter-streaming ions and double loss-cone electrons as evidence that the plasma was trapped on closed field lines, and acted as a source for the CAA emission across the polar regions. This suggests that the magnetosphere was almost entirely closed during these periods. We further argue that the closure occurred as a consequence of dual-lobe reconnection. Our finding forces a significant re-evaluation of the magnetic topology of the magnetosphere during periods of northwards IMF

Protocol for The Toxin Study: Understanding clinical and patient reported response of children and young people with cerebral palsy to intramuscular lower limb Botulinum neurotoxin-A injections, exploring all domains of the ICF. A pragmatic longitudinal observational study using a prospective one-group repeated measures design

This is the final version. Available from BMJ Publishing Group via the DOI in this record. Introduction: Botulinum neurotoxin-A (BoNT-A) is an accepted treatment modality for the management of hypertonia in children and young people with cerebral palsy (CYPwCP). Nevertheless, there are concerns about the long-term effects of BoNT-A, with a lack of consensus regarding the most meaningful outcome measures to guide its use. Most evidence to date is based on short-term outcomes, related to changes at impairment level (restrictions of body functions and structures), rather than changes in adaptive skills (enabling both activity and participation). The proposed study aims to evaluate clinical and patient reported outcomes in ambulant CYPwCP receiving lower limb BoNT-A injections over a 12-month period within all domains of the WHO’s International Classification of Functioning, Disability and Health and health-related quality of life (HRQoL). Methods and analysis: This pragmatic prospective longitudinal observational study will use a one-group repeated measures design. Sixty CYPwCP, classified as Gross Motor Function Classification System (GMFCS) levels I–III, aged between 4 and 18 years, will be recruited from an established movement disorder service in London, UK. Standardised clinical and patient reported outcome measures within all ICF domains; body structures and function, activity (including quality of movement), goal attainment, participation and HRQoL, will be collected preinjection and at 6 weeks, 6 months and up to 12 months postinjection. A representative subgroup of children and carers will participate in a qualitative component of the study, exploring how their experience of BoNT-A treatment relates to clinical outcome measures. Ethics and dissemination: Central London Research Ethics Committee has granted ethics approval (#IRAS 211617 #REC 17/LO/0579). Findings will be disseminated in peer-reviewed publications, conferences and via networks to participants and relevant stakeholders using a variety of accessible formats including social media.National Institute for Health Research (NIHR

Theory of Multidimensional Solitons

We review a number of topics germane to higher-dimensional solitons in Bose-Einstein condensates. For dark solitons, we discuss dark band and planar solitons; ring dark solitons and spherical shell solitons; solitary waves in restricted geometries; vortex rings and rarefaction pulses; and multi-component Bose-Einstein condensates. For bright solitons, we discuss instability, stability, and metastability; bright soliton engineering, including pulsed atom lasers; solitons in a thermal bath; soliton-soliton interactions; and bright ring solitons and quantum vortices. A thorough reference list is included.Comment: review paper, to appear as Chapter 5a in "Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P. G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez (Springer-Verlag

IIA/IIB Supergravity and Ten-forms

We perform a careful investigation of which p-form fields can be introduced consistently with the supersymmetry algebra of IIA and/or IIB ten-dimensional supergravity. In particular the ten-forms, also known as "top-forms", require a careful analysis since in this case, as we will show, closure of the supersymmetry algebra at the linear level does not imply closure at the non-linear level. Consequently, some of the (IIA and IIB) ten-form potentials introduced in earlier work of some of us are discarded. At the same time we show that new ten-form potentials, consistent with the full non-linear supersymmetry algebra can be introduced. We give a superspace explanation of our work. All of our results are precisely in line with the predictions of the E(11) algebra.Comment: 17 page

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Maximal supergravity in D=10: forms, Borcherds algebras and superspace cohomology

We give a very simple derivation of the forms of $N=2,D=10$ supergravity from supersymmetry and SL(2,\bbR) (for IIB). Using superspace cohomology we show that, if the Bianchi identities for the physical fields are satisfied, the (consistent) Bianchi identities for all of the higher-rank forms must be identically satisfied, and that there are no possible gauge-trivial Bianchi identities ($dF=0$) except for exact eleven-forms. We also show that the degrees of the forms can be extended beyond the spacetime limit, and that the representations they fall into agree with those predicted from Borcherds algebras. In IIA there are even-rank RR forms, including a non-zero twelve-form, while in IIB there are non-trivial Bianchi identities for thirteen-forms even though these forms are identically zero in supergravity. It is speculated that these higher-rank forms could be non-zero when higher-order string corrections are included.Comment: 15 pages. Published version. Some clarification of the tex

Total versus partial knee replacement in patients with medial compartment knee osteoarthritis : the TOPKAT RCT

Article history The research reported in this issue of the journal was funded by the HTA programme as project number 08/14/08. The contractual start date was in January 2010. The draft report began editorial review in February 2019 and was accepted for publication in October 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements TOPKAT study group Chief investigator David Beard. Trial co-investigators Nigel Arden (Oxford), Helen Campbell (Oxford), Marion Campbell (Aberdeen), Andrew Carr (Oxford), Jonathan Cook (Aberdeen then Oxford), Helen Doll (Oxford), Ray Fitzpatrick (Oxford), David Murray (Oxford) and Andrew Price (Oxford). Trial management Mayret Castillo (until 2011), Cushla Cooper, Loretta Davies, Anne Duncan (until 2017), Gordon Fernie, Sophie Halpin (until 2015) and Alison McDonald. Trial administration Katie Chegwin, Jiyang Li (until 2018), Elena Rabaiotti (until 2013), Sandra Regan (until 2012) and Victoria Stalker (until 2014). Data management Diana Collins (until 2013), Janice Cruden, Akiko Greshon, Kay Holland and Beverley Smith (until 2017). Database/programming management Gladys McPherson. Trial statisticians Charles Boachie (until 2013), Jemma Hudson and Graeme MacLennan. Health economists Helen Campbell (until 2015), Francesco Fusco (until 2018), Seamus Kent and Jose Leal. We would also like to thank Hannah Wilson (DPhil student, University of Oxford) for her help with the update to the literature search. Research teams We are grateful to the participants and research teams at collaborating hospital sites: Aneurin Bevan University Health Board, Royal Gwent Hospital Ruth Jenkins, Mark Lewis [principal investigator (PI)] and Witek Mintowt-Czyz. Belfast Health and Social Care Trust, Musgrove Park Hospital, Belfast David Beverland (PI), Leeann Bryce, Julie Catney, Ian Dobie, Emer Doran and Seamus O’Brien. Chesterfield Royal Hospital NHS Foundation Trust Fazal Ali, Heather Cripps, Amanda Whileman, Phil Williams (PI) and Julie Toms. County Durham and Darlington NHS Foundation Trust Ellen Brown, Gillian Horner, Andrew Jennings (PI) and Glynis Rose. East Lancashire Hospitals NHS Trust, Royal Blackburn Hospital Frances Bamford, Wendy Goddard, Hans Marynissen (PI), Haleh Peel and Lyndsey Richards. Great Western Hospitals NHS Foundation Trust, Swindon Amanda Bell, Sunny Deo, Sarah Grayland, David Hollinghurst, Suzannah Pegler, Venkat Satish (PI) and Claire Woodruffe. Harrogate and District NHS Foundation Trust, Harrogate Nick London (PI), David Duffy, Caroline Bennett and James Featherstone. Hull and East Yorkshire Hospitals NHS Trust Joss Cook, Kim Dearnley, Nagarajan Muthukumar (PI), Laura Onuoha and Sarah Wilson. Maidstone and Tunbridge Wells NHS Trust, Medway Sandhu Banher, Eunice Emeakaroha, Jamie Horohan, Sunil Jain (PI) and Susan Thompson. Mid Yorkshire Hospitals NHS Trust Sarah Buckley, Aaron Ng (PI), Ajit Shetty and Karen Simeson. Milton Keynes University Hospital NHS Foundation Trust Julian Flynn, Meryl Newsom, Cheryl Padilla-Harris and Oliver Pearce (PI). NHS Grampian, Woodend Hospital, Aberdeen James Bidwell (PI), Alison Innes, Winifred Culley and Bill Ledingham and Janis Stephen. North Bristol NHS Trust Rachel Bray, Hywel Davies, Debbie Delgado, Jonathan Eldridge, Leigh Morrison, James Murray (PI), Andrew Porteous and James Robinson. North Cumbria University Hospitals NHS Trust, Carlisle Matt Dawson (PI), Raj Dharmarajan, David Elson, Will Hage, Nicci Kelsall and Mike Orr. North Tees and Hartlepool NHS Foundation Trust, Stockton-On-Tees Jackie Grosvenor, SS Maheswaran (PI), Claire McCue, Hemanth Venkatesh, Michelle Wild and Deborah Wilson. Oxford University Hospitals NHS Trust, Nuffield Orthopaedic Centre Chris Dodd, William Jackson (PI), Pam Lovegrove, David Murray, Jennifer Piper and Andrew Price. Royal United Hospitals Bath NHS Foundation Trust, Bath Neil Bradbury, Lucy Clark, Stefanie Duncan, Genevieve Simpson and Allister Trezies (PI). Sherwood Forest Hospitals NHS Foundation Trust, Kings Mill Hospital, Sutton in Ashfield Vikram Desai (PI), Cheryl Heeley, Kramer Guy and Rosalyn Jackson. South Devon Healthcare NHS Foundation Trust, Torbay Alan Hall, Gordon Higgins (PI), Michael Hockings, David Isaac and Pauline Mercer. Stockport NHS Foundation Trust, Stockport Lindsey Barber, Helen Cochrane, Janette Curtis, Julie Grindey, David Johnson (PI), and Phil Turner. The Hillingdon Hospitals NHS Trust David Houlihan-Burne (PI), Briony Hill, Ron Langstaff and Mariam Nasseri. The Ipswich Hospital NHS Trust, Ipswich Mark Bowditch, Chris Martin, Steven Pryke, Bally Purewal, Chris Servant (PI), Sheeba Suresh and Claire Tricker. University Hospitals of Leicester NHS Trust, Leicester Robert Ashford, Manjit Attwal, Jeanette Bunga, Urjit Chatterji, Susan Cockburn, Colin Esler (PI), Steven Godsiff, Tim Green, Christina Haines and Subash Tandon. University Hospitals of North Midlands NHS Trust, Stoke on Trent Racquel Carpio, Sarah Griffiths, Natalie Grocott and Ian dos Remedios (PI). University Hospital Southampton NHS Foundation Trust David Barrett, Phil Chapman-Sheath, Caroline Grabau, Jane Moghul, William Tice (PI) and Catherine Trevithick. United Lincolnshire Hospitals NHS Trust, Boston Rajiv Deshmukh, Mandy Howes, Kimberley Netherton, Dipak Raj (PI) and Nikki Travis. United Lincolnshire Hospitals NHS Trust, Lincoln Mohammad Maqsood, Rebecca Norton, Farzana Rashid, Alison Raynor, Mark Rowsell and Karen Warner. We would like to thank the external members of the TSC and DMC for their advice and support for the project. Trial Steering Committee Donna Dodwell as our patient representative, Simon Donell (chairperson) (University of East Anglia), Shawn Tavares (Royal Berkshire Hospital) and Jonathan Waite (South Warwickshire NHS Foundation Trust). Data Monitoring Committee Karen Barker (Oxford University Hospitals NHS Foundation Trust), Gordon Murray (chairperson) (University of Edinburgh) and Hamish Simpson (University of Edinburgh). Independent review and interpretation of results Professor David Torgerson (University of York). Professor Chris Maher (University of Sydney). Mr Peter Brownson (The Royal Liverpool and Broadgreen University Hospitals NHS Trust). Professor Simon Donell (University of East Anglia, Norwich). Mr Mark Mullins (Abertawe Bro Morgannwg University Health Board). Professor Jane Blazeby (Bristol University).Peer reviewedPublisher PD