Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

The medium-term sustainability of organisational innovations in the national health service

Background: There is a growing recognition of the importance of introducing new ways of working into the UK's National Health Service (NHS) and other health systems, in order to ensure that patient care is provided as effectively and efficiently as possible. Researchers have examined the challenges of introducing new ways of working-'organisational innovations'-into complex organisations such as the NHS, and this has given rise to a much better understanding of how this takes place-and why seemingly good ideas do not always result in changes in practice. However, there has been less research on the medium-and longer-term outcomes for organisational innovations and on the question of how new ways of working, introduced by frontline clinicians and managers, are sustained and become established in day-to-day practice. Clearly, this question of sustainability is crucial if the gains in patient care that derive from organisational innovations are to be maintained, rather than lost to what the NHS Institute has called the 'improvement-evaporation effect'. Methods: The study will involve research in four case-study sites around England, each of which was successful in sustaining its new model of service provision beyond an initial period of pilot funding for new genetics services provided by the Department of Health. Building on findings relating to the introduction and sustainability of these services already gained from an earlier study, the research will use qualitative methods-in-depth interviews, observation of key meetings, and analysis of relevant documents-to understand the longer-term challenges involved in each case and how these were surmounted. The research will provide lessons for those seeking to sustain their own organisational innovations in wide-ranging clinical areas and for those designing the systems and organisations that make up the NHS, to make them more receptive contexts for the sustainment of innovation. Discussion: Through comparison and contrast across four sites, each involving different organisational innovations, different forms of leadership, and different organisational contexts to contend with, the findings of the study will have wide relevance. The research will produce outputs that are useful for managers and clinicians responsible for organisational innovation, policy makers and senior managers, and academics

Giant Anharmonic Phonon Scattering in PbTe

Understanding the microscopic processes affecting the bulk thermal conductivity is crucial to develop more efficient thermoelectric materials. PbTe is currently one of the leading thermoelectric materials, largely thanks to its low thermal conductivity. However, the origin of this low thermal conductivity in a simple rocksalt structure has so far been elusive. Using a combination of inelastic neutron scattering measurements and first-principles computations of the phonons, we identify a strong anharmonic coupling between the ferroelectric transverse optic (TO) mode and the longitudinal acoustic (LA) modes in PbTe. This interaction extends over a large portion of reciprocal space, and directly affects the heat-carrying LA phonons. The LA-TO anharmonic coupling is likely to play a central role in explaining the low thermal conductivity of PbTe. The present results provide a microscopic picture of why many good thermoelectric materials are found near a lattice instability of the ferroelectric type

Characteristics associated with quality of life among people with drug-resistant epilepsy

Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants’ mean score was 66, with a wide range (25–99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy

Control of magnetic anisotropy by orbital hybridization in (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattice

The asymmetry of chemical nature at the hetero-structural interface offers an unique opportunity to design desirable electronic structure by controlling charge transfer and orbital hybridization across the interface. However, the control of hetero-interface remains a daunting task. Here, we report the modulation of interfacial coupling of (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattices by manipulating the periodic thickness with n unit cells of SrTiO3 and n unit cells La0.67Sr0.33MnO3. The easy axis of magnetic anisotropy rotates from in-plane (n = 10) to out-of-plane (n = 2) orientation at 150 K. Transmission electron microscopy reveals enlarged tetragonal ratio > 1 with breaking of volume conservation around the (La0.67Sr0.33MnO3)n/(SrTiO3)n interface, and electronic charge transfer from Mn to Ti 3d orbitals across the interface. Orbital hybridization accompanying the charge transfer results in preferred occupancy of 3d3z2-r2 orbital at the interface, which induces a stronger electronic hopping integral along the out-of-plane direction and corresponding out-of-plane magnetic easy axis for n = 2. We demonstrate that interfacial orbital hybridization in superlattices of strongly correlated oxides may be a promising approach to tailor electronic and magnetic properties in device applications

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Uptake of home-based voluntary HIV testing in sub-Saharan Africa: a systematic review and meta-analysis

Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Theta-paced flickering between place-cell maps in the hippocampus

The ability to recall discrete memories is thought to depend on the formation of attractor states in recurrent neural networks. In such networks, representations can be reactivated reliably from subsets of the cues that were present when the memory was encoded, at the same time as interference from competing representations is minimized. Theoretical studies have pointed to the recurrent CA3 system of the hippocampus as a possible attractor network. Consistent with predictions from these studies, experiments have shown that place representations in CA3 and downstream CA1 tolerate small changes in the configuration of the environment but switch to uncorrelated representations when dissimilarities become larger. The kinetics supporting such network transitions, at the subsecond time scale, is poorly understood, however. Here we show that instantaneous transformation of the spatial context (\u2018teleportation\u2019) does not change the hippocampal representation all at once but is followed by temporary bistability in the discharge activity of CA3 ensembles. Rather than sliding through a continuum of intermediate activity states, the CA3 network undergoes a short period of competitive flickering between pre-formed representations for past and present environment, before settling on the latter. Network flickers are extremely fast, often with complete replacement of the active ensemble from one theta cycle to the next. Within individual cycles, segregation is stronger towards the end, when firing starts to decline, pointing to the theta cycle as a temporal unit for expression of attractor states in the hippocampus. Repetition of pattern-completion processes across successive theta cycles may facilitate error correction and enhance discriminative power in the presence of weak and ambiguous input cues

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U