Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes

Funded by •ERC. Grant Number: 284167 •NIH. Grant Number: 1RO1DK0921127-01 •NWO. Grant Numbers: 463-06-001, 451-04-034Peer reviewedPublisher PD

Pharmacy-led implementation of evidence based medicine in primary care : Evaluating Diuretics in Usual Care study (EVIDENCE)

Introduction Obtaining evidence of comparative effectiveness and safety of widely prescribed drugs in a timely cost-effective way is emerging as a major global challenge for healthcare systems. The Evaluating Drugs in Normal Care (EVIDENCE) programme addresses this challenge through novel methodology. We describe an exemplar pilot study comparing thiazide type diuretics for hypertension. Method Patients prescribed either indapamide or bendroflumethiazide for hypertension were identified in each primary care practice recruited. Random allocation of a prescribing policy for one or other of these drugs was then applied to the whole practice and where required repeat prescriptions were switched to comply with randomised policy. Patients were informed of the potential switch by letter with the option to discuss further with the study team and/or opt-out of the switch. Routinely collected hospitalization and death data in NHS will be used to compare cardiovascular event rates between the two policies. Results We found bendroflumethiazide was prescribed to 78% of patients prescribed either of these drugs despite recent NICE preference for indapamide. 29 primary care practices in 5 Scottish NHS boards were recruited and 14 randomised to indapamide and 15 to bendroflumethiazide creating a study population of 5985 patients. Less than 0.23% of patients opted out. Conclusion This pilot study demonstrated the feasibility and cost efficiency of the EVIDENCE approach. A relatively large study was generated rapidly with negligible disruption to practice workflows. EVIDENCE methodology offers a novel way to compare the effectiveness of a wide range of medicines where there is clinical equipoise.Non peer reviewe

Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas

Identification of novel prognostic biomarkers typically requires a large dataset which provides sufficient statistical power for discovery research. To this end, we took advantage of the high‐throughput data from The Cancer Genome Atlas (TCGA) to identify a set of prognostic biomarkers in head and neck squamous cell carcinomas (HNSCC) including oropharyngeal squamous cell carcinoma (OPSCC) and other subtypes. In this study, we analyzed miRNA‐seq data obtained from TCGA patients to identify prognostic biomarkers for OPSCC. The identified miRNAs were further tested with an independent cohort. miRNA‐seq data from TCGA was also analyzed to identify prognostic miRNAs in oral cavity squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC). Our study identified that miR‐193b‐3p and miR‐455‐5p were positively associated with survival, and miR‐92a‐3p and miR‐497‐5p were negatively associated with survival in OPSCC. A combined expression signature of these four miRNAs was prognostic of overall survival in OPSCC, and more importantly, this signature was validated in an independent OPSCC cohort. Furthermore, we identified four miRNAs each in OSCC and LSCC that were prognostic of survival, and combined signatures were specific for subtypes of HNSCC. A robust 4‐miRNA prognostic signature in OPSCC, as well as prognostic signatures in other subtypes of HNSCC, was developed using sequencing data from TCGA as the primary source. This demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care

On post-Lie algebras, Lie--Butcher series and moving frames

Pre-Lie (or Vinberg) algebras arise from flat and torsion-free connections on differential manifolds. They have been studied extensively in recent years, both from algebraic operadic points of view and through numerous applications in numerical analysis, control theory, stochastic differential equations and renormalization. Butcher series are formal power series founded on pre-Lie algebras, used in numerical analysis to study geometric properties of flows on euclidean spaces. Motivated by the analysis of flows on manifolds and homogeneous spaces, we investigate algebras arising from flat connections with constant torsion, leading to the definition of post-Lie algebras, a generalization of pre-Lie algebras. Whereas pre-Lie algebras are intimately associated with euclidean geometry, post-Lie algebras occur naturally in the differential geometry of homogeneous spaces, and are also closely related to Cartan's method of moving frames. Lie--Butcher series combine Butcher series with Lie series and are used to analyze flows on manifolds. In this paper we show that Lie--Butcher series are founded on post-Lie algebras. The functorial relations between post-Lie algebras and their enveloping algebras, called D-algebras, are explored. Furthermore, we develop new formulas for computations in free post-Lie algebras and D-algebras, based on recursions in a magma, and we show that Lie--Butcher series are related to invariants of curves described by moving frames.Comment: added discussion of post-Lie algebroid

Hamiltonian dynamics and constrained variational calculus: continuous and discrete settings

The aim of this paper is to study the relationship between Hamiltonian dynamics and constrained variational calculus. We describe both using the notion of Lagrangian submanifolds of convenient symplectic manifolds and using the so-called Tulczyjew's triples. The results are also extended to the case of discrete dynamics and nonholonomic mechanics. Interesting applications to geometrical integration of Hamiltonian systems are obtained.Comment: 33 page

Understanding Anthropological Understanding: for a merological anthropology

In this paper I argue for a merological anthropology in which ideas of ‘partiality’ and ‘practical adequacy’ provide a way out of the impasse of relativism which is implied by post-modernism and the related abandonment of a concern with ‘truth’. Ideas such as ‘aptness’ and ‘faithfulness’ enable us to re-establish empirical foundations without having to espouse a simple realism which has been rightly criticised. Ideas taken from ethnomethodology, particularly the way we bootstrap from ‘practical adequacy’ to ‘warrants for confidence’ point to a merological anthropology in which we recognize that we do not and cannot know everything, but that we can have reasons for being confident in the little we know

Does offering an incentive payment improve recruitment to clinical trials and increase the proportion of socially deprived and elderly participants?

BACKGROUND: Patient recruitment into clinical trials is a major challenge, and the elderly, socially deprived and those with multiple comorbidities are often underrepresented. The idea of paying patients an incentive to participate in research is controversial, and evidence is needed to evaluate this as a recruitment strategy. METHOD: In this study, we sought to assess the impact on clinical trial recruitment of a £100 incentive payment and whether the offer of this payment attracted more elderly and socially deprived patients. A total of 1,015 potential patients for five clinical trials (SCOT, FAST and PATHWAY 1, 2 and 3) were randomised to receive either a standard trial invitation letter or a trial invitation letter containing an incentive offer of £100. To receive payment, patients had to attend a screening visit and consent to be screened (that is, sign a consent form). To maintain equality, eventually all patients who signed a consent form were paid £100. RESULTS: The £100 incentive offer increased positive response to the first invitation letter from 24.7% to 31.6%, an increase of 6.9% (P < 0.05). The incentive offer increased the number of patients signing a consent form by 5.1% (P < 0.05). The mean age of patients who responded positively to the invitation letter was 66.5 ± 8.7 years, whereas those who responded negatively were significantly older, with a mean age of 68.9 ± 9.0 years. The incentive offer did not influence the age of patients responding. The incentive offer did not improve response in the most socially deprived areas, and the response from patients in these areas was significantly lower overall. CONCLUSION: A £100 incentive payment offer led to small but significant improvements in both patient response to a clinical trial invitation letter and in the number of patients who consented to be screened. The incentive payment did not attract elderly or more socially deprived patients. TRIAL REGISTRATIONS: Standard care versus Celecoxib Outcome Trial (SCOT) (ClinicalTrials.gov identifier: NCT00447759). Febuxostat versus Allopurinol Streamlined Trial (FAST) (EudraCT number: 2011-001883-23). Prevention and Treatment of Hypertension with Algorithm Guided Therapy (British Heart Foundation funded trials) (PATHWAY) 1: Monotherapy versus dual therapy for initiating treatment (EudraCT number: 2008-007749-29). PATHWAY 2: Optimal treatment of drug-resistant hypertension (EudraCT number: 2008-007149-30). PATHWAY 3: Comparison of single and combination diuretics in low-renin hypertension (EudraCT number: 2009-010068-41). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0582-8) contains supplementary material, which is available to authorized users

Comparison Studies of Finite Momentum Correlators on Anisotropic and Isotropic Lattices

We study hadronic two- and three-point correlators relevant for heavy to light pseudoscalar meson semi-leptonic decays, using Symanzik improved glue, D234 light quark and NRQCD heavy quark actions. Detailed comparisons are made between simulations on anisotropic and isotropic lattices involving finite momentum hadrons. We find evidence that having an anisotropy helps in extracting better signals at higher momenta. Initial results for the form factors f_+(q^2) and f_0(q^2) are presented with tree-level matching of the lattice heavy-light currents.Comment: 43 pages with 50 postscript figure