CONSORT 2010 statement: extension to randomised pilot and feasibility trials [on behalf of the PAFS consensus group*]

The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply. The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist. The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number. This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials. Editor’s note: In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites

The mystery of the cerebellum: clues from experimental and clinical observations

Abstract The cerebellum has a striking homogeneous cytoarchitecture and participates in both motor and non-motor domains. Indeed, a wealth of evidence from neuroanatomical, electrophysiological, neuroimaging and clinical studies has substantially modified our traditional view on the cerebellum as a sole calibrator of sensorimotor functions. Despite the major advances of the last four decades of cerebellar research, outstanding questions remain regarding the mechanisms and functions of the cerebellar circuitry. We discuss major clues from both experimental and clinical studies, with a focus on rodent models in fear behaviour, on the role of the cerebellum in motor control, on cerebellar contributions to timing and our appraisal of the pathogenesis of cerebellar tremor. The cerebellum occupies a central position to optimize behaviour, motor control, timing procedures and to prevent body oscillations. More than ever, the cerebellum is now considered as a major actor on the scene of disorders affecting the CNS, extending from motor disorders to cognitive and affective disorders. However, the respective roles of the mossy fibres, the climbing fibres, cerebellar cortex and cerebellar nuclei remains unknown or partially known at best in most cases. Research is now moving towards a better definition of the roles of cerebellar modules and microzones. This will impact on the management of cerebellar disorders

Structure and Dynamics of Amyloid-β Segmental Polymorphisms

Conceived and designed the experiments: WB UH. Performed the experiments: WB. Analyzed the data: WB UH. Contributed reagents/materials/analysis tools: WB UH. Wrote the paper: WB UH.It is believed that amyloid-beta (Aβ) aggregates play a role in the pathogenesis of Alzheimer’s disease. Aβ molecules form β-sheet structures with multiple interaction sites. This polymorphism gives rise to differences in morphology, physico-chemical property and level of cellular toxicity. We have investigated the conformational stability of various segmental polymorphisms using molecular dynamics simulations and find that the segmental polymorphic models of Aβ retain a U-shaped architecture. Our results demonstrate the importance of inter-sheet side chain-side chain contacts, hydrophobic contacts among the strands (β1 and β2) and of salt bridges in stabilizing the aggregates. Residues in β-sheet regions have smaller fluctuation while those at the edge and loop region are more mobile. The inter-peptide salt bridges between Asp23 and Lys28 are strong compared to intra-chain salt bridge and there is an exchange of the inter-chain salt-bridge with intra-chain salt bridge. As our results suggest that Aβ exists under physiological conditions as an ensemble of distinct segmental polymorphs, it may be necessary to account in the development of therapeutics for Alzheimer’s disease the differences in structural stability and aggregation behavior of the various Aβ polymorphic forms.Yeshttp://www.plosone.org/static/editorial#pee