High-dimensional simplexes for supermetric search

In a metric space, triangle inequality implies that, for any three objects, a triangle with edge lengths corresponding to their pairwise distances can be formed. The n-point property is a generalisation of this where, for any (n+1) objects in the space, there exists an n-dimensional simplex whose edge lengths correspond to the distances among the objects. In general, metric spaces do not have this property; however in 1953, Blumenthal showed that any semi-metric space which is isometrically embeddable in a Hilbert space also has the n-point property. We have previously called such spaces supermetric spaces, and have shown that many metric spaces are also supermetric, including Euclidean, Cosine, Jensen-Shannon and Triangular spaces of any dimension. Here we show how such simplexes can be constructed from only their edge lengths, and we show how the geometry of the simplexes can be used to determine lower and upper bounds on unknown distances within the original space. By increasing the number of dimensions, these bounds converge to the true distance. Finally we show that for any Hilbert-embeddable space, it is possible to construct Euclidean spaces of arbitrary dimensions, from which these lower and upper bounds of the original space can be determined. These spaces may be much cheaper to query than the original. For similarity search, the engineering tradeoffs are good: we show significant reductions in data size and metric cost with little loss of accuracy, leading to a significant overall improvement in exact search performance

The Improving Rural Cancer Outcomes (IRCO) Trial: A factorial clusterrandomised controlled trial of a complex intervention to reduce time to diagnosis in rural patients with cancer in Western Australia: A study protocol

Introduction: While overall survival for most common cancers in Australia is improving, the rural-urban differential has been widening, with significant excess deaths due to lung, colorectal, breast and prostate cancer in regional Australia. Internationally a major focus on understanding variations in cancer outcomes has been later presentation to healthcare and later diagnosis. Approaches to reducing time to diagnosis of symptomatic cancer include public symptom awareness campaigns and interventions in primary care to improve early cancer detection. This paper reports the protocol of a factorial cluster-randomised trial of community and general practice (GP) level interventions to reduce the time to diagnosis of cancer in rural Western Australia (WA). Methods and analysis: The community intervention is a symptom awareness campaign tailored for rural Australians delivered through a community engagement model. The GP intervention includes a resource card with symptom risk assessment charts and local referral pathways implemented through multiple academic detailing visits and case studies. Participants are eligible if recently diagnosed with breast, colorectal, lung or prostate cancer who reside in specific regions of rural WA with a planned sample size of 1350. The primary outcome is the Total Diagnostic Interval, defined as the duration from first symptom (or date of cancer screening test) to cancer diagnosis. Secondary outcomes include cancer stage, healthcare utilisation, disease-free status, survival at 2 and 5 years and cost-effectiveness. Ethics and dissemination: Ethics approval has been granted by the University of Western Australia and from all relevant hospital recruitment sites in WA. Results: Results of this trial will be reported in peerreviewed publications and in conference presentations. Trial registration number: Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12610000872033

Asteroseismology

Asteroseismology is the determination of the interior structures of stars by using their oscillations as seismic waves. Simple explanations of the astrophysical background and some basic theoretical considerations needed in this rapidly evolving field are followed by introductions to the most important concepts and methods on the basis of example. Previous and potential applications of asteroseismology are reviewed and future trends are attempted to be foreseen.Comment: 38 pages, 13 figures, to appear in: "Planets, Stars and Stellar Systems", eds. T. D. Oswalt et al., Springer Verla

Feller Processes: The Next Generation in Modeling. Brownian Motion, L\'evy Processes and Beyond

We present a simple construction method for Feller processes and a framework for the generation of sample paths of Feller processes. The construction is based on state space dependent mixing of L\'evy processes. Brownian Motion is one of the most frequently used continuous time Markov processes in applications. In recent years also L\'evy processes, of which Brownian Motion is a special case, have become increasingly popular. L\'evy processes are spatially homogeneous, but empirical data often suggest the use of spatially inhomogeneous processes. Thus it seems necessary to go to the next level of generalization: Feller processes. These include L\'evy processes and in particular Brownian motion as special cases but allow spatial inhomogeneities. Many properties of Feller processes are known, but proving the very existence is, in general, very technical. Moreover, an applicable framework for the generation of sample paths of a Feller process was missing. We explain, with practitioners in mind, how to overcome both of these obstacles. In particular our simulation technique allows to apply Monte Carlo methods to Feller processes.Comment: 22 pages, including 4 figures and 8 pages of source code for the generation of sample paths of Feller processe

Solidaires, unitaires et démocratiques: social movement unionism and beyond?

A contribution to a Special Issue on trade union renewal that focuses on this topic in relation to the radical French trade union Solidaires, Unitaires et Démocratiques (SUD)

Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney

BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats. For each period, urine and blood samples were collected at baseline and within 48 h of treatment starting. Plasma renin activity (PRA), plasma and urinary aldosterone concentrations, glomerular filtration rate (GFR) and 24 h urinary volumes, electrolytes and eicosanoids (PGE(2), 6-keto-PGF1(α,) TxB(2)), renal injury biomarker excretions [N-acetyl-beta-D-glucosaminidase (NAG) and Gamma-Glutamyltransferase] were measured. Urine volume (24 h) and urinary sodium, chloride and calcium excretions increased from baseline with all treatments. Plasma creatinine increased with all treatments except placebo, whereas GFR was significantly decreased from baseline only with ketoprofen. PRA increased significantly with placebo and once daily robenacoxib and the increase was significantly higher with placebo compared to ketoprofen (10.5 ± 4.4 vs 4.9 ± 5.0 ng ml(−1) h(−1)). Urinary aldosterone excretion increased with all treatments but this increase was inhibited by 75 % with ketoprofen and 65 % with once daily robenacoxib compared to placebo. Urinary PGE(2) excretion decreased with all treatments and excretion was significantly lower with ketoprofen compared to placebo. Urinary TxB(2) excretion was significantly increased from baseline only with placebo. NAG increased from baseline with all treatments. Immunohistochemistry on post-mortem renal specimens, obtained from a different group of cats that died naturally of non-renal causes, suggested constitutive COX-1 and COX-2 co-localization in many renal structures including the macula densa (MD). CONCLUSIONS: These data suggest that both COX-1 and COX-2 could generate the signal from the MD to the renin secreting cells in cats exposed to furosemide. Co-localization of COX isoenzymes in MD cells supports the functional data reported here. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0598-z) contains supplementary material, which is available to authorized users

Developing Single-Molecule TPM Experiments for Direct Observation of Successful RecA-Mediated Strand Exchange Reaction

RecA recombinases play a central role in homologous recombination. Once assembled on single-stranded (ss) DNA, RecA nucleoprotein filaments mediate the pairing of homologous DNA sequences and strand exchange processes. We have designed two experiments based on tethered particle motion (TPM) to investigate the fates of the invading and the outgoing strands during E. coli RecA-mediated pairing and strand exchange at the single-molecule level in the absence of force. TPM experiments measure the tethered bead Brownian motion indicative of the DNA tether length change resulting from RecA binding and dissociation. Experiments with beads labeled on either the invading strand or the outgoing strand showed that DNA pairing and strand exchange occurs successfully in the presence of either ATP or its non-hydrolyzable analog, ATPγS. The strand exchange rates and efficiencies are similar under both ATP and ATPγS conditions. In addition, the Brownian motion time-courses suggest that the strand exchange process progresses uni-directionally in the 5′-to-3′ fashion, using a synapse segment with a wide and continuous size distribution

Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction

BACKGROUND: There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment. METHODS: Using the UK Biobank resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations [PCE] or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals. RESULTS: The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared with 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI, 4.7–7.0). When individuals were stratified into age-by-sex subgroups, the improvement was larger for all subgroups (range, 8.3%–15.4%), with the best performance in 40- to 54-year-old men (15.4% [95% CI, 11.6–19.3]). Comparable results were found using a different risk tool (QRISK3) and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12 000 deaths in the United States over a 5-year period. CONCLUSIONS: An IRT that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person’s polygenic risk

Ecology: a prerequisite for malaria elimination and eradication

* Existing front-line vector control measures, such as insecticide-treated nets and residual sprays, cannot break the transmission cycle of Plasmodium falciparum in the most intensely endemic parts of Africa and the Pacific * The goal of malaria eradication will require urgent strategic investment into understanding the ecology and evolution of the mosquito vectors that transmit malaria * Priority areas will include understanding aspects of the mosquito life cycle beyond the blood feeding processes which directly mediate malaria transmission * Global commitment to malaria eradication necessitates a corresponding long-term commitment to vector ecolog

The quest for the solar g modes

Solar gravity modes (or g modes) -- oscillations of the solar interior for which buoyancy acts as the restoring force -- have the potential to provide unprecedented inference on the structure and dynamics of the solar core, inference that is not possible with the well observed acoustic modes (or p modes). The high amplitude of the g-mode eigenfunctions in the core and the evanesence of the modes in the convection zone make the modes particularly sensitive to the physical and dynamical conditions in the core. Owing to the existence of the convection zone, the g modes have very low amplitudes at photospheric levels, which makes the modes extremely hard to detect. In this paper, we review the current state of play regarding attempts to detect g modes. We review the theory of g modes, including theoretical estimation of the g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the techniques that have been used to try to detect g modes. We review results in the literature, and finish by looking to the future, and the potential advances that can be made -- from both data and data-analysis perspectives -- to give unambiguous detections of individual g modes. The review ends by concluding that, at the time of writing, there is indeed a consensus amongst the authors that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie