The cost-effectiveness of an early interventional strategy in non-ST-elevation acute coronary syndrome based on the RITA 3 trial

The published version of the aritcle can be found at the link below.Background: Evidence suggests that an early interventional strategy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) can improve health outcomes but also increase costs when compared with a conservative strategy.Objective: The aim of this study was to assess the cost-effectiveness of an early interventional strategy in different risk groups from a UK health-service perspective.Design: Decision-analytic model based on randomised clinical trial data.Main outcome measures: Costs in UK Sterling at 2003/2004 prices and quality-adjusted life years (QALYs) combined into an incremental cost-effectiveness ratio.Methods: Data from the third Randomised Intervention Trial of unstable Angina (RITA 3) was employed to estimate rates of cardiovascular death and myocardial infarction, costs and health-related quality of life. Cost-effectiveness was estimated over patients' lifetimes within the decision-analytic model.Results: The mean incremental cost per QALY gained for an early interventional strategy was approximately £55000, £22000 and £12000 for patients at low, intermediate and high risk, respectively. The early interventional strategy is approximately 1%, 35% and 95% likely to be cost-effective for patients at low, intermediate and high risk, respectively, at a threshold of £20000 per QALY. The cost-effectiveness of early intervention in low-risk patients is sensitive to assumptions about the duration of the treatment effect.Conclusion: An early interventional strategy in patients presenting with NSTE-ACS is likely to be considered cost-effective for patients at high and intermediate risk, but this is less likely to be the case for patients at low risk

Exploratory topic modeling with distributional semantics

As we continue to collect and store textual data in a multitude of domains, we are regularly confronted with material whose largely unknown thematic structure we want to uncover. With unsupervised, exploratory analysis, no prior knowledge about the content is required and highly open-ended tasks can be supported. In the past few years, probabilistic topic modeling has emerged as a popular approach to this problem. Nevertheless, the representation of the latent topics as aggregations of semi-coherent terms limits their interpretability and level of detail. This paper presents an alternative approach to topic modeling that maps topics as a network for exploration, based on distributional semantics using learned word vectors. From the granular level of terms and their semantic similarity relations global topic structures emerge as clustered regions and gradients of concepts. Moreover, the paper discusses the visual interactive representation of the topic map, which plays an important role in supporting its exploration.Comment: Conference: The Fourteenth International Symposium on Intelligent Data Analysis (IDA 2015

Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight.

BACKGROUND: Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed. RESULTS: We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI. CONCLUSION: This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight

Extensive winter subglacial water storage beneath the Greenland Ice Sheet

This is the final version of the article. Available from AGU via the DOI in this record.Surface meltwater that reaches the base of the Greenland Ice Sheet exerts a fundamental impact on ice flow, but observations of catchment-wide movement and distribution of subglacial water remain limited. Using radar-sounding data from two seasons, we identify the seasonal distribution of subglacial water in western Greenland. Our analysis provides evidence of widespread subglacial water storage beneath Greenland in the wintertime. The winter storage is located primarily on bedrock ridges with higher bed elevations in excess of 200 m. During the melt season water moves to the subglacial troughs. This inverse relationship with topography indicates that the material properties of the glacier bed strongly influence subglacial drainage development. Both the spatial variations in bed properties and the initial state of the subglacial hydrology system at the start of the melt season lead to differing glacier dynamical responses to surface melting across the Greenland Ice Sheet.W.C. is a recipient of the NASA Earth and Space Science Fellowship. D.M.S. is supported by a grant from the NASA Cryospheric Sciences Program. H.S. is supported by grants from the NASA Cryospheric Sciences and Sea Level Rise Programs. T.T.C and R.E.B are supported by grants from National Science Foundation (NSF) and NASA Cryospheric Sciences. S.P. is supported by the Natural Environment Research Council’s Centre for Polar Observatio

Salivary Testosterone and Sexual Function and Behavior in Men and Women: Findings from the Third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Using data from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) we examined associations between salivary testosterone (Sal-T) and sexual function and behavior. Single morning saliva samples were self-collected from a subsample of participants aged 18–74 years and analyzed using mass spectrometry. 1,599 men and 2,123 women were included in the analysis (40.6% of those invited to provide a sample). We adjusted for confounders in a stepwise manner: in model 1 we adjusted for age only; model 2 for age, season and relationship status, and model 3 we added BMI and self-reported health. In the fully adjusted models, among men, Sal-T was positively associated with both partnered sex (vaginal sex and concurrent partners) and masturbation. Among women, Sal-T was positively associated with masturbation, the only association with partnered sex was with ever experience of same-sex sex. We found no clear association between Sal-T and sexual function. Our study contributes toward addressing the sparsity of data outside the laboratory on the differences between men and women in the relationship between T and sexual function and behavior. To our knowledge, this is the first population study, among men and women, using a mass spectrometry Sal-T assay to do so

The Mitochondrial Genome of the Legume Vigna radiata and the Analysis of Recombination across Short Mitochondrial Repeats

The mitochondrial genomes of seed plants are exceptionally fluid in size, structure, and sequence content, with the accumulation and activity of repetitive sequences underlying much of this variation. We report the first fully sequenced mitochondrial genome of a legume, Vigna radiata (mung bean), and show that despite its unexceptional size (401,262 nt), the genome is unusually depauperate in repetitive DNA and "promiscuous" sequences from the chloroplast and nuclear genomes. Although Vigna lacks the large, recombinationally active repeats typical of most other seed plants, a PCR survey of its modest repertoire of short (38–297 nt) repeats nevertheless revealed evidence for recombination across all of them. A set of novel control assays showed, however, that these results could instead reflect, in part or entirely, artifacts of PCR-mediated recombination. Consequently, we recommend that other methods, especially high-depth genome sequencing, be used instead of PCR to infer patterns of plant mitochondrial recombination. The average-sized but repeat- and feature-poor mitochondrial genome of Vigna makes it ever more difficult to generalize about the factors shaping the size and sequence content of plant mitochondrial genomes

Acceptability of a first-line anti-tuberculosis formulation for children: qualitative data from the SHINE trial.

SETTING: We conducted a qualitative exploration into the palatability and acceptability of a novel fixed-dose combination (FDC) anti-tuberculosis drug. This study was nested in the SHINE (Shorter treatment for minimal TB in children) trial, which compares the safety and efficacy of treating non-severe drug-susceptible tuberculosis (TB) with a 6 vs. 4 months anti-tuberculosis regimen in children aged 0-16 years. Participants were recruited in Cape Town, South Africa.OBJECTIVE: To describe the palatability and acceptability of a FDC of rifampicin, isoniazid and pyrazinamide among South African children and their caregivers in the SHINE trial.METHODS: We conducted 20 clinic observations of treatment administration, during which we conducted 16 semi-structured interviews with children and their caregivers. Data were organised thematically to report on experiences with administering and ingesting the FDC.RESULTS: Children and caregivers' experiences varied from delight to disgust. In general, participants said that the FDC compared favourably to other formulations. Pragmatic challenges such as dissolving the FDC and the time required to administer the FDC impeded caregivers' ability to integrate treatment into their daily routines. Drug manipulation was common among caregivers to improve TB treatment administration.CONCLUSION: This novel FDC appears acceptable for children, albeit with practical challenges to administration. Scale-up of FDC use should include supplementary intervention components to support caregivers

Transformation Pathways of Silica under High Pressure

Concurrent molecular dynamics simulations and ab initio calculations show that densification of silica under pressure follows a ubiquitous two-stage mechanism. First, anions form a close-packed sub-lattice, governed by the strong repulsion between them. Next, cations redistribute onto the interstices. In cristobalite silica, the first stage is manifest by the formation of a metastable phase, which was observed experimentally a decade ago, but never indexed due to ambiguous diffraction patterns. Our simulations conclusively reveal its structure and its role in the densification of silica.Comment: 14 pages, 4 figure

Evolution of predator dispersal in relation to spatio-temporal prey dynamics : how not to get stuck in the wrong place!

Peer reviewedPublisher PD