Cortisol Release From Adipose Tissue by 11β-Hydroxysteroid Dehydrogenase Type 1 in Humans

OBJECTIVE—11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol from cortisone. 11β-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11β-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11β-HSD1 from adipose tissue and its effect on portal vein cortisol concentrations have not been quantified in vivo

Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain

Effect of temperature and strain rate on the compressive behaviour of supramolecular polyurethane

Supramolecular polyurethanes (SPUs) possess thermoresponsive and thermoreversible properties, and those characteristics are highly desirable in both bulk commodity and value-added applications such as adhesives, shape-memory materials, healable coatings and lightweight, impact-resistant structures (e.g. protection for mobile electronics). A better understanding of the mechanical properties, especially the rate and temperature sensitivity, of these materials are required to assess their suitability for different applications. In this paper, a newly developed SPU with tuneable thermal properties was studied, and the response of this SPU to compressive loading over strain rates from 10−3 to 104 s−1 was presented. Furthermore, the effect of temperature on the mechanical response was also demonstrated. The sample was tested using an Instron mechanical testing machine for quasi-static loading, a home-made hydraulic system for moderate rates and a traditional split Hopkinson pressure bars (SHPBs) for high strain rates. Results showed that the compression stress-strain behaviour was affected significantly by the thermoresponsive nature of SPU, but that, as expected for polymeric materials, the general trends of the temperature and the rate dependence mirror each other. However, this behaviour is more complicated than observed for many other polymeric materials, as a result of the richer range of transitions that influence the behaviour over the range of temperatures and strain rates tested

MUSE-ALMA Halos XI: Gas flows in the circumgalactic medium

The flow of gas into and out of galaxies leaves traces in the circumgalactic medium which can then be studied using absorption lines towards background quasars. We analyse 27 log(N_HI) > 18.0 HI absorbers at z = 0.2 to 1.4 from the MUSE-ALMA Halos survey with at least one galaxy counterpart within a line of sight velocity of +/-500 km s^{-1}. We perform 3D kinematic forward modelling of these associated galaxies to examine the flow of dense, neutral gas in the circumgalactic medium. From the VLT/MUSE, HST broadband imaging and VLT/UVES and Keck/HIRES high-resolution UV quasar spectroscopy observations, we compare the impact parameters, star-formation rates and stellar masses of the associated galaxies with the absorber properties. We find marginal evidence for a bimodal distribution in azimuthal angles for strong HI absorbers, similar to previous studies of the MgII and OVI absorption lines. There is no clear metallicity dependence on azimuthal angle and we suggest a larger sample of absorbers are required to fully test the relationship predicted by cosmological hydrodynamical simulations. A case-by-case study of the absorbers reveals that ten per cent of absorbers are consistent with gas accretion, up to 30 per cent trace outflows while the remainder trace gas in the galaxy disk, the intragroup medium and low-mass galaxies below the MUSE detection limit. Our results highlight that the baryon cycle directly affects the dense neutral gas required for star-formation and plays a critical role in galaxy evolution.Comment: 13 pages, 6 figures, 12 pages of appendix. Accepted for publication in MNRA

MUSE-ALMA Haloes IX: Morphologies and Stellar Properties of Gas-rich Galaxies

Understanding how galaxies interact with the circumgalactic medium (CGM) requires determining how galaxies morphological and stellar properties correlate with their CGM properties. We report an analysis of 66 well-imaged galaxies detected in HST and VLT MUSE observations and determined to be within $\pm$500 km s$^{-1}$ of the redshifts of strong intervening quasar absorbers at $0.2 \lesssim z \lesssim 1.4$ with H I column densities $N_{\rm H I}$ $>$ $10^{18}$ $\rm cm^{-2}$. We present the geometrical properties (S\'ersic indices, effective radii, axis ratios, and position angles) of these galaxies determined using GALFIT. Using these properties along with star formation rates (SFRs, estimated using the H$\alpha$ or [O II] luminosity) and stellar masses ($M_{*}$ estimated from spectral energy distribution fits), we examine correlations among various stellar and CGM properties. Our main findings are as follows: (1) SFR correlates well with $M_{*}$, and most absorption-selected galaxies are consistent with the star formation main sequence (SFMS) of the global population. (2) More massive absorber counterparts are more centrally concentrated and are larger in size. (3) Galaxy sizes and normalized impact parameters correlate negatively with $N_{\rm H I}$, consistent with higher $N_{\rm H I}$ absorption arising in smaller galaxies, and closer to galaxy centers. (4) Absorption and emission metallicities correlate with $M_{*}$ and sSFR, implying metal-poor absorbers arise in galaxies with low past star formation and faster current gas consumption rates. (5) SFR surface densities of absorption-selected galaxies are higher than predicted by the Kennicutt-Schmidt relation for local galaxies, suggesting a higher star formation efficiency in the absorption-selected galaxies.Comment: Accepted for publication in MNRAS, 25 pages, 19 figure

In-reach specialist nursing teams for residential care homes : uptake of services, impact on care provision and cost-effectiveness

Background: A joint NHS-Local Authority initiative in England designed to provide a dedicated nursing and physiotherapy in-reach team (IRT) to four residential care homes has been evaluated.The IRT supported 131 residents and maintained 15 'virtual' beds for specialist nursing in these care homes. Methods: Data captured prospectively (July 2005 to June 2007) included: numbers of referrals; reason for referral; outcome (e.g. admission to IRT bed, short-term IRT support); length of stay in IRT; prevented hospital admissions; early hospital discharges; avoided nursing home transfers; and detection of unrecognised illnesses. An economic analysis was undertaken. Results: 733 referrals were made during the 2 years (range 0.5 to 13.0 per resident per annum)resulting in a total of 6,528 visits. Two thirds of referrals aimed at maintaining the resident's independence in the care home. According to expert panel assessment, 197 hospital admissions were averted over the period; 20 early discharges facilitated; and 28 resident transfers to a nursing home prevented. Detection of previously unrecognised illnesses accounted for a high number of visits. Investment in IRT equalled £44.38 per resident per week. Savings through reduced hospital admissions, early discharges, delayed transfers to nursing homes, and identification of previously unrecognised illnesses are conservatively estimated to produce a final reduction in care cost of £6.33 per resident per week. A sensitivity analysis indicates this figure might range from a weekly overall saving of £36.90 per resident to a 'worst case' estimate of £2.70 extra expenditure per resident per week. Evaluation early in implementation may underestimate some cost-saving activities and greater savings may emerge over a longer time period. Similarly, IRT costs may reduce over time due to the potential for refinement of team without major loss in effectiveness. Conclusion: Introduction of a specialist nursing in-reach team for residential homes is at least cost neutral and, in all probability, cost saving. Further benefits include development of new skills in the care home workforce and enhanced quality of care. Residents are enabled to stay in familiar surroundings rather than unnecessarily spending time in hospital or being transferred to a higher dependency nursing home setting

Exploring What Factors Mediate Treatment Effect: Example of the STarT Back Study High-Risk Intervention

Interventions developed to improve disability outcomes for low back pain (LBP) often show only small effects. Mediation analysis was used to investigate what led to the effectiveness of the STarT Back trial, a large primary care-based trial that treated patients consulting with LBP according to their risk of a poor outcome. The high-risk subgroup, randomized to receive either psychologically-informed physiotherapy (n = 93) or current best care (n = 45), was investigated to explore pain-related distress and pain intensity as potential mediators of the relationship between treatment allocation and change in disability. Structural equation modeling was used to generate latent variables of pain-related distress and pain intensity from measures used to identify patients at high risk (fear-avoidance beliefs, depression, anxiety, and catastrophizing thoughts). Outcome was measured using the Roland–Morris Disability Questionnaire. Change in pain-related distress and pain intensity were found to have a significant mediating effect of .25 (standardized estimate, bootstrapped 95% confidence interval, .09–.39) on the relationship between treatment group allocation and change in disability outcome. This study adds to the evidence base of treatment mediation studies in pain research and the role of distress in influencing disability outcome in those with complex LBP. Perspective Mediation analysis using structural equation modeling found that change in pain-related distress and pain intensity mediated treatment effect in the STarT Back trial. This type of analysis can be used to gain further insight into how interventions work, and lead to the design of more effective interventions in future

Delivering an Optimised Behavioural Intervention (OBI) to people with low back pain with high psychological risk; results and lessons learnt from a feasibility randomised controlled trial of Contextual Cognitive Behavioural Therapy (CCBT) vs. Physiotherapy

Background: Low Back Pain (LBP) remains a common and costly problem. Psychological obstacles to recovery have been identified, but psychological and behavioural interventions have produced only moderate improvements. Reviews of trials have suggested that the interventions lack clear theoretical basis, are often compromised by low dose, lack of fidelity, and delivery by non-experts. In addition, interventions do not directly target known risk mechanisms. We identified a theory driven intervention (Contexual Cognitive Behavioural Therapy, CCBT) that directly targets an evidence-based risk mechanism (avoidance and ensured dose and delivery were optimised. This feasibility study was designed to test the credibility and acceptability of optimised CCBT against physiotherapy for avoidant LBP patients, and to test recruitment, delivery of the intervention and response rates prior to moving to a full definitive trial. Methods: A randomised controlled feasibility trial with patients randomised to receive CCBT or physiotherapy. CCBT was delivered by trained supervised psychologists on a one to one basis and comprised up to 8 one-hour sessions. Physiotherapy comprised back to fitness group exercises with at least 60 % of content exercise-based. Patients were eligible to take part if they had back pain for more than 3 months, and scored above a threshold indicating fear avoidance, catastrophic beliefs and distress. Results: 89 patients were recruited. Uptake rates were above those predicted. Scores for credibility and acceptability of the interventions met the set criteria. Response rates at three and six months fell short of the 75 % target. Problems associated with poor response rates were identified and successfully resolved, rates increased to 77 % at 3 months, and 68 % at 6 months. Independent ratings of treatment sessions indicated that CCBT was delivered to fidelity. Numbers were too small for formal analysis. Although average scores for acceptance were higher in the CCBT group than in the group attending physiotherapy (increase of 7.9 versus 5.1) and change in disability and pain from baseline to 6 months were greater in the CCBT group than in the physiotherapy group, these findings should be interpreted with caution. Conclusions: CCBT is a credible and acceptable intervention for LBP patients who exhibit psychological obstacles to recovery