Delivering the Future: Evaluation of a Multidisciplinary Clinical Leadership Programme in NHS Scotland.

The Delivering the Future (DtF) leadership programme was established in 2005 to strengthen senior clinical leadership capacity and capability across NHS Scotland. This paper reports on an evaluation of the programme to determine the extent to which the programme outcomes had been achieved. Sixty-seven (57%) programme participants responded to a questionnaire survey about their experience, and semi-structured interviews were conducted with participants (n=8) and senior leaders (n=7) at NHS Board level. The programme was highly regarded by participants and strategic level leads. The majority of DtF participants had been promoted or taken on expanded roles since completing the programme, taking on greater leadership responsibility. The programme was seen to be a significant influence on accelerating the progression of individuals to these roles, and in developing skills to perform at a senior leadership level. The significant investment in the programme was thought to be worthwhile in terms of wider benefits, albeit with a need to make better collective use of the alumni at a national level

New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism

Design of low-cost ionic liquids for lignocellulosic biomass pretreatment

The cost of ionic liquids (ILs) is one of the main impediments to IL utilization in the cellulosic biorefinery, especially in the pretreatment step. In this study, a number of ionic liquids were synthesized with the goal of optimizing solvent cost and stability whilst demonstrating promising processing potential. To achieve this, inexpensive feedstocks such as sulfuric acid and simple amines were combined into a range of protic ionic liquids containing the hydrogen sulfate [HSO] anion. The performance of these ionic liquids was compared to a benchmark system containing the IL 1-ethyl-3-methylimidazolium acetate [CCim][OAc]. The highest saccharification yields were observed for the triethylammonium hydrogen sulfate IL, which was 75% as effective as the benchmark system. Techno-economic modeling revealed that this promising and yet to be optimized yield was achieved at a fraction of the processing cost. This study demonstrates that some ILs can compete with the cheapest pretreatment chemicals, such as ammonia, in terms of effectiveness and process cost, removing IL cost as a barrier to the economic viability of IL-based biorefineries

Mendelian randomization for studying the effects of perturbing drug targets [version 1; peer review: awaiting peer review]

Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse effects. Large databases of summary level genetic association data are increasingly available and can be leveraged to identify and validate variants that serve as proxies for drug target perturbation. As with all empirical research, Mendelian randomization has limitations including genetic confounding, its consideration of lifelong effects, and issues related to heterogeneity across different tissues and populations. When appropriately applied, Mendelian randomization provides a useful empirical framework for using population level data to improve the success rates of the drug development pipeline

Mendelian randomization for studying the effects of perturbing drug targets [version 2; peer review: 3 approved, 1 approved with reservations]

Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse effects. Large databases of summary level genetic association data are increasingly available and can be leveraged to identify and validate variants that serve as proxies for drug target perturbation. As with all empirical research, Mendelian randomization has limitations including genetic confounding, its consideration of lifelong effects, and issues related to heterogeneity across different tissues and populations. When appropriately applied, Mendelian randomization provides a useful empirical framework for using population level data to improve the success rates of the drug development pipeline

Interventions to improve exercise behaviour in sedentary people living with and beyond cancer: a systematic review

Background: To systematically review the effects of interventions to improve exercise behaviour in sedentary people living with and beyond cancer. Methods: Only randomised controlled trials (RCTs) that compared an exercise intervention to a usual care comparison in sedentary people with a homogeneous primary cancer diagnosis, over the age of 18 years were eligible. The following electronic databases were searched: Cochrane Central Register of Controlled Trials MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; SportDiscus; PEDro from inception to August 2012. Results: Fourteen trials were included in this review, involving a total of 648 participants. Just six trials incorporated prescriptions that would meet current recommendations for aerobic exercise. However, none of the trials included in this review reported intervention adherence of 75% or more for a set prescription that would meet current aerobic exercise guidelines. Despite uncertainty around adherence in many of the included trials, the interventions caused improvements in aerobic exercise tolerance at 8–12 weeks (SMD=0.73, 95% CI=0.51–0.95) in intervention participants compared with controls. At 6 months, aerobic exercise tolerance is also improved (SMD=0.70, 95% CI=0.45–0.94), although four of the five trials had a high risk of bias; hence, caution is warranted in its interpretation. Conclusion: Expecting the majority of sedentary survivors to achieve the current exercise guidelines is likely to be unrealistic. As with all well-designed exercise programmes, prescriptions should be designed around individual capabilities and frequency, duration and intensity or sets, repetitions, intensity of resistance training should be generated on this basis

Spanish validation of Bad Sobernheim Stress Questionnaire (BSSQ (brace).es) for adolescents with braces

<p>Abstract</p> <p>Background</p> <p>As a result of scientific and medical professionals gaining interest in Stress and Health Related Quality of Life (HRQL), the aim of our research is, thus, to validate into Spanish the German questionnaire <b>Bad Sobernheim Stress Questionnaire (BSSQ) (mit Korsett)</b>, for adolescents wearing braces.</p> <p>Methods</p> <p>The methodology used adheres to literature on trans-cultural adaptation by doing a translation and a back translation; it involved 35 adolescents, ages ranging between 10 and 16, with Adolescent Idiopathic Scoliosis (AIS) and wearing the same kind of brace (Rigo System Chêneau Brace). The materials used were a socio-demographics data questionnaire, the SRS-22 and the Spanish version of BSSQ(brace).es. The statistical analysis calculated the reliability (test-retest reliability and internal consistency) and the validity (convergent and construct validity) of the BSSQ (brace).es.</p> <p>Results</p> <p>BSSQ(brace).es is reliable because of its satisfactory internal consistency (Cronbach's alpha coefficient was 0.809, p < 0.001) and temporal stability (test-retest method with a Pearson correlation coefficient of 0.902 (p < 0.01)).</p> <p>It demonstrated convergent validity with SRS-22 since the Pearson correlation coefficient was 0.656 (p < 0.01). By undertaking an Exploratory Principal Components Analysis, a latent structure was found based on two Components which explicate the variance at 60.8%.</p> <p>Conclusions</p> <p>BSSQ (brace).es is reliable and valid and can be used with Spanish adolescents to assess the stress level caused by the brace.</p

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives