Trial designWe present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of... Show moreTrial designWe present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.MethodsThe study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study.ConclusionsThere is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the at risk state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA.Trial registrationCurrent Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014. Show less
Performances of solo keyboard repertoire can sound more or less polyphonic depending on the performer’s use of divergence in expression. Rather than being a purely cerebral experience, this... Show morePerformances of solo keyboard repertoire can sound more or less polyphonic depending on the performer’s use of divergence in expression. Rather than being a purely cerebral experience, this expressive divergence is situated in an ecological relationship between keyboard and player where the gestural dynamics of technique and musicianship overlap. Specific body schemata relating to expressive divergence are therefore foundational to the interpretive freedom of the performer in creating polyphonic expression, and feature transparently in the musical result. This dissertation theorises expressive divergence by examining the embodiment of single voices through the hierarchical structuring of coarticulation, and by showing how these multi-layered gestures combine in the polyphony of expression. This performative view of polyphony is contextualised not only in musical practice, but also in the wider interdisciplinary use of polyphony as a metaphor. Single-player polyphonic expression is shown to enact or demonstrate an inner experience of the plurality of subjective agency, an experience made possible by its embodied dimension. Besides verbalising and theorising polyphonic expression, this dissertation provides experiments and exercises useful for developing such a practice, as well as examples of its application in concert Show less