Research into practice : collaboration for leadership in applied health research and care (CLAHRC) for Nottinghamshire, Derbyshire, Lincolnshire (NDL)

To address the problem of translation from research-based evidence to routine healthcare practice, the Collaboration for Leadership in Applied Health Research and Care for Nottinghamshire, Derbyshire, and Lincolnshire (CLAHRC-NDL) was funded by the National Institute for Health Research as one of nine CLAHRCs across England. This paper outlines the underlying theory and its application that CLAHRC-NDL has adopted, as a case example that might be generalised to practice outside the CLAHRC, in comparison to alternative models of implementation

Lyapunov instability for a periodic Lorentz gas thermostated by deterministic scattering

In recent work a deterministic and time-reversible boundary thermostat called thermostating by deterministic scattering has been introduced for the periodic Lorentz gas [Phys. Rev. Lett. {\bf 84}, 4268 (2000)]. Here we assess the nonlinear properties of this new dynamical system by numerically calculating its Lyapunov exponents. Based on a revised method for computing Lyapunov exponents, which employs periodic orthonormalization with a constraint, we present results for the Lyapunov exponents and related quantities in equilibrium and nonequilibrium. Finally, we check whether we obtain the same relations between quantities characterizing the microscopic chaotic dynamics and quantities characterizing macroscopic transport as obtained for conventional deterministic and time-reversible bulk thermostats.Comment: 18 pages (revtex), 7 figures (postscript

What do I do now? Intolerance of uncertainty is associated with discrete patterns of anticipatory physiological responding to different contexts

Heightened physiological responses to uncertainty are a common hallmark of anxiety disorders. Many separate studies have examined the relationship between individual differences in intolerance of uncertainty (IU) and physiological responses to uncertainty during different contexts. Despite this there is a scarcity of research examining the extent to which individual differences in IU are related to shared or discrete patterns of anticipatory physiological responding across different contexts. Anticipatory physiological responses to uncertainty were assessed in three different contexts (associative threat learning and extinction, threat uncertainty, decision-making) within the same sample (n = 45). During these tasks, behavioural responses (i.e. reaction times, choices), skin conductance and corrugator supercilli activity were recorded. In addition, self-reported IU and trait anxiety were measured. IU was related to both skin conductance and corrugator supercilii activity for the associative threat learning and extinction context, and decision-making context. However, trait anxiety was related to corrugator supercilii activity during the threat uncertainty context. Ultimately, this research helps us further tease apart the role of IU on different aspects of anticipation (i.e. valence and arousal) across contexts, which will be relevant for future IU-related models of psychopathology

A Synthetic Loop Replacement Peptide That Blocks Canonical NFâ κB Signaling

Aberrant canonical NFâ κB signaling is implicated in diseases from autoimmune disorders to cancer. A major therapeutic challenge is the need for selective inhibition of the canonical pathway without impacting the many nonâ canonical NFâ κB functions. Here we show that a selective peptideâ based inhibitor of canonical NFâ κB signaling, in which a hydrogen bond in the NBD peptide is synthetically replaced by a nonâ labile bond, shows an about 10â fold increased potency relative to the original inhibitor. Not only is this molecule, NBD2, a powerful tool for dissection of canonical NFâ κB signaling in disease models and healthy tissues, the success of the synthetic loop replacement suggests that the general strategy could be useful for discovering modulators of the many proteinâ protein interactions mediated by such structures.A peptideâ based inhibitor of canonical NFâ κB signaling, in which a hydrogen bond in the NBD peptide is synthetically replaced by a nonâ labile bond, shows an about 10â fold increased potency relative to the original inhibitor. The success of the synthetic replacement of a peptide loop suggests that the general strategy could be broadly useful for discovering modulators of many proteinâ protein interactions mediated by such structures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135096/1/anie201607990.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135096/2/anie201607990-sup-0001-misc_information.pd

Developing a framework for the analysis of power through depotentia

Stakeholder participation in tourism policy-making is usually perceived as providing a means of empowerment. However participatory processes drawing upon stakeholders from traditionally empowered backgrounds may provide the means of removing empowerment from stakeholders. Such an outcome would be in contradiction to the claims that participatory processes improve both inclusivity and sustainability. In order to form an understanding of the sources through which empowerment may be removed, an analytical perspective has been developed deriving from Lukes�s views of power dating from 1974. This perspective considers the concept of depotentia as the removal of �power to� without speculating upon the underlying intent and also provides for the multidimensionality of power to be examined within a single study. The application of this analytical perspective has been tested upon findings of the government-commissioned report of the Countryside and Community Research Unit in 2005. The survey and report investigated the progress of Local Access Forums in England created in response to the Countryside and Rights of Way Act 2000. Consideration of the data from this perspective permits the classification of individual sources of depotentia which can each be addressed and potentially enable stakeholder groups to reverse loss of empowerment where it has occurred

General practitioners' views on reattribution for patients with medically unexplained symptoms: a questionnaire and qualitative study

Background: The successful introduction of new methods for managing medically unexplained symptoms in primary care is dependent to a large degree on the attitudes, experiences and expectations of practitioners. As part of an exploratory randomised controlled trial of reattribution training, we sought the views of participating practitioners on patients with medically unexplained symptoms, and on the value of and barriers to the implementation of reattribution in practice. Methods: A nested attitudinal survey and qualitative study in sixteen primary care teams in north-west England. All practitioners participating in the trial (n = 74) were invited to complete a structured survey. Semi-structured interviews were undertaken with a purposive sub-sample of survey respondents, using a structured topic guide. Interview transcripts were used to identify key issues, concepts and themes, which were grouped to construct a conceptual framework: this framework was applied systematically to the data. Results: Seventy (95%) of study participants responded to the survey. Survey respondents often found it stressful to work with patients with medically unexplained symptoms, though those who had received reattribution training were more optimistic about their ability to help them. Interview participants trained in reattribution (n = 12) reported that reattribution increased their confidence to practice in a difficult area, with heightened awareness, altered perceptions of these patients, improved opportunities for team-building and transferable skills. However general practitioners also reported potential barriers to the implementation of reattribution in routine clinical practice, at the level of the patient, the doctor, the consultation, diagnosis and the healthcare context. Conclusion: Reattribution training increases practitioners' sense of competence in managing patients with medically unexplained symptoms. However, barriers to its implementation are considerable, and frequently lie outside the control of a group of practitioners generally sympathetic to patients with medically unexplained symptoms and the purpose of reattribution. These findings add further to the evidence of the difficulty of implementing reattribution in routine general practice

Fatigue Intervention by Nurses Evaluation - The FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610]

Background: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition characterised primarily by severe, disabling fatigue, of unknown origin, which has a poor prognosis and serious personal and economic consequences. Evidence for the effectiveness of any treatment for CFS/ME in primary care, where most patients are seen, is sparse. Recently, a brief, pragmatic treatment for CFS/ME, based on a physiological dysregulation model of the condition, was shown to be successful in improving fatigue and physical functioning in patients in secondary care. The treatment involves providing patients with a readily understandable explanation of their symptoms, from which flows the rationale for a graded rehabilitative plan, developed collaboratively with the therapist. The present trial will test the effectiveness and cost-effectiveness of pragmatic rehabilitation when delivered by specially trained general nurses in primary care. We selected a client-centred counselling intervention, called supportive listening, as a comparison treatment. Counselling has been shown to be as effective as cognitive behaviour therapy for treating fatigue in primary care, is more readily available, and controls for supportive therapist contact time. Our control condition is treatment as usual by the general practitioner (GP). Methods and design: This study protocol describes the design of an ongoing, single-blind, pragmatic randomized controlled trial of a brief (18 week) self-help treatment, pragmatic rehabilitation, delivered by specially trained nurse-therapists in patients' homes, compared with nurse-therapist delivered supportive listening and treatment as usual by the GP. An economic evaluation, taking a societal viewpoint, is being carried out alongside the clinical trial. Three adult general nurses were trained over a six month period to deliver the two interventions. Patients aged over 18 and fulfilling the Oxford criteria for CFS are assessed at baseline, after the intervention, and again one year later. Primary outcomes are self-reported physical functioning and fatigue at one year, and will be analysed on an intention-to-treat basis. A qualitative study will examine the interventions' mechanisms of change, and also GPs' drivers and barriers towards referral

Localized behavior in the Lyapunov vectors for quasi-one-dimensional many-hard-disk systems

We introduce a definition of a "localization width" whose logarithm is given by the entropy of the distribution of particle component amplitudes in the Lyapunov vector. Different types of localization widths are observed, for example, a minimum localization width where the components of only two particles are dominant. We can distinguish a delocalization associated with a random distribution of particle contributions, a delocalization associated with a uniform distribution and a delocalization associated with a wave-like structure in the Lyapunov vector. Using the localization width we show that in quasi-one-dimensional systems of many hard disks there are two kinds of dependence of the localization width on the Lyapunov exponent index for the larger exponents: one is exponential, and the other is linear. Differences, due to these kinds of localizations also appear in the shapes of the localized peaks of the Lyapunov vectors, the Lyapunov spectra and the angle between the spatial and momentum parts of the Lyapunov vectors. We show that the Krylov relation for the largest Lyapunov exponent $\lambda\sim-\rho\ln\rho$ as a function of the density $\rho$ is satisfied (apart from a factor) in the same density region as the linear dependence of the localization widths is observed. It is also shown that there are asymmetries in the spatial and momentum parts of the Lyapunov vectors, as well as in their $x$ and $y$-components.Comment: 41 pages, 21 figures, Manuscript including the figures of better quality is available from http://www.phys.unsw.edu.au/~gary/Research.htm

Lamotrigine versus inert placebo in the treatment of borderline personality disorder: study protocol for a randomized controlled trial and economic evaluation

Background: People with borderline personality disorder (BPD) experience rapid and distressing changes in mood, poor social functioning and have high rates of suicidal behaviour. Several small scale studies suggest that mood stabilizers may produce short-term reductions in symptoms of BPD, but have not been large enough to fully examine clinical and cost-effectiveness. Methods/Design: A two parallel-arm, placebo controlled randomized trial of usual care plus either lamotrigine or an inert placebo for people aged over 18 who are using mental health services and meet diagnostic criteria for BPD. We will exclude people with comorbid bipolar affective disorder or psychosis, those already taking a mood stabilizer, those who speak insufficient English to complete the baseline assessment and women who are pregnant or contemplating becoming pregnant. Those meeting inclusion criteria and provide written informed consent will be randomized to up to 200mg of lamotrigine per day or an inert placebo (up to 400mg if taking combined oral contraceptives).Participants will be randomized via a remote web-based system using permuted stacked blocks stratified by study centre, severity of personality disorder, and level of bipolarity. Follow-up assessments will be conducted by masked researchers 12, 24 weeks, and 52 weeks after randomization. The primary outcome is the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). The secondary outcomes are depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment, adverse events and withdrawal of trial medication due to adverse effects. The main analyses will use intention to treat without imputation of missing data. The economic evaluation will take an NHS/Personal Social Services perspective. A cost-utility analysis will compare differences in total costs and differences in quality of life using QALYs derived from the EQ-5D. Discussion: The evidence base for the use of pharmacological treatments for people with borderline personality disorder is poor. In this trial we will examine the clinical and cost-effectiveness of lamotrigine to assess what if any impact offering this has on peoples’ mental health, social functioning, and use of other medication and other resources. Trial registration: Current Controlled Trials ISRCTN90916365 (registered 01/08/2012