Estimands: bringing clarity and focus to research questions in clinical trials

Precise specification of the research question and associated treatment effect of interest is essential in clinical research, yet recent work shows that they are often incompletely specified. The ICH E9 (R1) Addendum on Estimands and Sensitivity Analysis in Clinical Trials introduces a framework that supports researchers in precisely and transparently specifying the treatment effect they aim to estimate in their clinical trial. In this paper, we present practical examples to demonstrate to all researchers involved in clinical trials how estimands can help them to specify the research question, lead to a better understanding of the treatment effect to be estimated and hence increase the probability of success of the trial

Neighbourhood blue space, health and wellbeing: The mediating role of different types of physical activity

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground: Evidence suggests that living near blue spaces such as the coast, lakes and rivers may be good for health and wellbeing. Although greater levels of physical activity (PA) may be a potential mechanism, we know little about the types of PA that might account for this. Objectives: To explore the mediating role of: a) ‘watersports’ (e.g. sailing/canoeing); b) ‘on-land outdoor PA’ in natural/mixed settings (e.g. walking/running/cycling); and, c) ‘indoor/other PA’ (e.g. gym/squash) in the relationships between residential blue space availability and health outcomes. Methods: Using data from the Health Survey for England (n = 21,097), we constructed a path model to explore whether weekly volumes of each PA type mediate any of the relationships between residential blue space availability (coastal proximity and presence of freshwater) and self-reported general and mental health, controlling for green space density and a range of socio-economic factors at the individual- and area-level. Results: Supporting predictions, living nearer the coast was associated with better self-reported general and mental health and this was partially mediated by on-land outdoor PA (primarily walking). Watersports were more common among those living within 5kms of the coast, but did not mediate associations between coastal proximity and health. Presence of freshwater in the neighbourhood was associated with better mental health, but this effect was not mediated by PA. Conclusions: Although nearby blue spaces offer potentially easier access to watersports, relatively few individuals in England engage in them and thus they do not account for positive population health associations. Rather, the benefits to health from coastal living seem, at least in part, due to participation in land-based outdoor activities (especially walking). Further research is needed to explore the mechanisms behind the relationship between freshwater presence and mental health.Kone FoundationEuropean CommissionNational Institute for Health Research (NIHR)European Union Horizon 202

Efficient coupling into slow light photonic crystal waveguide without transition region: Role of evanescent modes

We show that efficient coupling between fast and slow photonic crystal waveguide modes is possible, provided that there exist strong evanescent modes to match the waveguide fields across the interface. Evanescent modes are required when the propagating modes have substantially different modal fields, which occurs, for example, when coupling an index-guided mode and a gap-guided mode. ©2009 Optical Society of America

Efficient slow-light coupling in a photonic crystal waveguide without transition region

We consider the coupling into a slow mode that appears near an inflection point in the band structure of a photonic crystal waveguide. Remarkably, the coupling into this slow mode, which has a group index ng > 1000, can be essentially perfect without any transition region. We show that this efficient coupling occurs thanks to an evanescent mode in the slow medium, which has appreciable amplitude and helps satisfy the boundary conditions but does not transport any energy. © 2008 Optical Society of America

Symmetry and degeneracy in microstructured optical fibers

The symmetry of an optical waveguide determines its modal degeneracies. A fiber with rotational symmetry of order higher than 2 has modes that either are nondegenerate and support the complete fiber symmetry or are twofold degenerate pairs of lower symmetry. The latter case applies to the fundamental modes of perfect microstructured optical fibers, guaranteeing that such fibers are not birefringent. We explore two numerical methods and demonstrate their agreement with these symmetry constraints. © 2001 Optical Society of America

Confinement losses in microstructured optical fibers

We describe a multipole formulation that can be used for high-accuracy calculations of the full complex propagation constant of a microstructured optical fiber with a finite number of holes. We show how the imaginary part of the microstructure, which describes confinement losses not associated with absorption, varies with hole size, the number of rings of holes, and wavelength, and give the minimum number of rings of holes required for a specific loss for given parameters. © 2001 Optical Society of America

Calculations of air-guided modes in photonic crystal fibers using the multipole method

We demonstrate that a combination of multipole and Bloch methods is well suited for calculating the modes of air core photonic crystal fibers. This includes determining the reflective properties of the cladding, which is a prerequisite for the modal calculations. We demonstrate that in the presence of absorption, the modal losses can be substantially smaller than in the corresponding bulk medium. © 2001 Optical Society of America

Modulation of somatosensory processing by action.

Psychophysical evidence suggests that sensations arising from our own movements are diminished when predicted by motor forward models and that these models may also encode the timing and intensity of movement. Here we report a functional magnetic resonance imaging study in which the effects on sensation of varying the occurrence, timing and force of movements were measured. We observed that tactile-related activity in a region of secondary somatosensory cortex is reduced when sensation is associated with movement and further that this reduction is maximal when movement and sensation occur synchronously. Motor force is not represented in the degree of attenuation but rather in the magnitude of this region's response. These findings provide neurophysiological correlates of previously-observed behavioural forward-model phenomena, and advocate the adopted approach for the study of clinical conditions in which forward-model deficits have been posited to play a crucial role