Improving personalised care, through the development of a service evaluation tool to assess, understand and monitor delivery.

Systematically implementing personalised care has far reaching benefits to individuals, communities and health and social care systems. If done well, personalised care can result in better health outcomes and experiences, more efficient use of health services and reduced health inequalities. Despite these known benefits, implementation of personalised care has been slow. Evaluation is an important step towards achieving the ambition of universally delivered personalised care. There are currently few comprehensive assessments or tools that are designed to understand the implementation of personalised care at a service or system level, or the cultural, practical and behavioural factors influencing this. The aim of this paper is to describe the development and testing of a system-wide evaluation tool. The tool offers a process through which healthcare systems can better understand the current delivery of personalised care and the factors influencing this. With a focus on implementation, the development of the tool was informed by the Consolidated Framework for Implementation Research, and its content is structured using behaviour change theory (COM-B Theory of Behaviour Change Model). The tool consists of four mirrored surveys, which were developed using an iterative exploratory design. This included a series of testing cycles, in which its structure and content were continually refined. To date, it has been used by 24 clinical services, involving 397 service users, 313 front-line practitioners, 73 service managers and 40 commissioners. These services have used the evaluation process to initiate quality improvement, targeted at one of the more aspects of personalised care. The use of the COM-B model increases the likelihood of those improvements being sustained, through identification of the core factors that enable or limit personalised care behaviours among healthcare staff. We have shown this process to be applicable in a wide range of settings, thus it potentially has broad applicability as a tool for cultural change and quality improvement. The next stage of this work will focus on implementation and evaluation, to fully understand if and how the tool can be used to drive improvements in personalised care delivery.

Point absorbers in Advanced LIGO.

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers). This analysis predicts that the power-dependent reduction in interferometer performance will significantly degrade maximum stored power by up to 50% and, hence, limit GW sensitivity, but it suggests system wide corrections that can be implemented in current and future GW detectors. This is particularly pressing given that future GW detectors call for an order of magnitude more stored power than currently used in Advanced LIGO in Observing Run 3. We briefly review strategies to mitigate the effects of point absorbers in current and future GW wave detectors to maximize the success of these enterprises.

Observation of Parametric Instability in Advanced LIGO.

Parametric instabilities have long been studied as a potentially limiting effect in high-power interferometric gravitational wave detectors. Until now, however, these instabilities have never been observed in a kilometer-scale interferometer. In this Letter, we describe the first observation of parametric instability in a gravitational wave detector, and the means by which it has been removed as a barrier to progress.

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs.

The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans.

The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs.

The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies.

Bilayer thickness and thermal response of dimyristoylphosphatidylcholine unilamellar vesicles containing cholesterol, ergosterol and lanosterol: a small-angle neutron scattering study.

Small-angle neutron scattering (SANS) measurements are performed on pure dimyristoyl phosphatidylcholine (DMPC) unilamellar vesicles (ULV) and those containing either 20 or 47 mol% cholesterol, ergosterol or lanosterol. From the SANS data, we were able to determine the influence of these sterols on ULV bilayer thickness and vesicle area expansion coefficients. While these parameters have been determined previously for membranes containing cholesterol, to the best of our knowledge, this is the first time such results have been presented for membranes containing the structurally related sterols, ergosterol and lanosterol. At both molar concentrations and at temperatures ranging from 10 to 45 degrees C, the addition of the different sterols leads to increases in bilayer thickness, relative to pure DMPC. We observe large differences in the influence of these sterols on the membrane thermal area expansion coefficient. All three sterols, however, produce very similar changes to membrane thickness.