WISDOM: history and early demise - was it inevitable?

In 1989, the UK Medical Research Council (MRC) agreed that, if feasible, a randomized controlled trial to assess the long-term risks and benefits of hormone replacement therapy (HRT) was a priority. Feasibility work began in 1990 and demonstrated that a large-scale multicenter trial was possible. An application for funding for a main trial was submitted to MRC in 1993 and, after extensive review, funding was released in late 1996. Set-up work for the trial - the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) - began in 1997 with recruitment in 1999. In October 2002, following the early discontinuation of one arm of the US Women's Health Initiative HRT trial, the MRC decided to stop the WISDOM trial. This article, by the principal UK investigators of WISDOM, sets out the background and history of the trial

Progressive managerial bonuses in a spatial Bertrand duopoly

The relationship of managerial bonuses and profit maximization is interesting both from an economic and a managerial viewpoint. Our contribution to this literature is showing that progressive managerial bonuses can increase profits in a spatial Bertrand competition, and furthermore they can help collusion

Community rotorcraft air transportation benefits and opportunities

Information about rotorcraft that will assist community planners in assessing and planning for the use of rotorcraft transportation in their communities is provided. Information useful to helicopter researchers, manufacturers, and operators concerning helicopter opportunities and benefits is also given. Three primary topics are discussed: the current status and future projections of rotorcraft technology, and the comparison of that technology with other transportation vehicles; the community benefits of promising rotorcraft transportation opportunities; and the integration and interfacing considerations between rotorcraft and other transportation vehicles. Helicopter applications in a number of business and public service fields are examined in various geographical settings

Self-Similar Evaporation of a Rigidly-Rotating Cosmic String Loop

The gravitational back-reaction on a certain type of rigidly-rotating cosmic string loop, first discovered by Allen, Casper and Ottewill, is studied at the level of the weak-field approximation. The near-field metric perturbations are calculated and used to construct the self-acceleration vector of the loop. Although the acceleration vector is divergent at the two kink points on the loop, its net effect on the trajectory over a single oscillation period turns out to be finite. The net back-reaction on the loop over a single period is calculated using a method due to Quashnock and Spergel, and is shown to induce a uniform shrinkage of the loop while preserving its original shape. The loop therefore evolves by self-similar evaporation.Comment: 41 pages, 5 figures. Accepted for publication in Classical and Quantum Gravit

A topos for algebraic quantum theory

The aim of this paper is to relate algebraic quantum mechanics to topos theory, so as to construct new foundations for quantum logic and quantum spaces. Motivated by Bohr's idea that the empirical content of quantum physics is accessible only through classical physics, we show how a C*-algebra of observables A induces a topos T(A) in which the amalgamation of all of its commutative subalgebras comprises a single commutative C*-algebra. According to the constructive Gelfand duality theorem of Banaschewski and Mulvey, the latter has an internal spectrum S(A) in T(A), which in our approach plays the role of a quantum phase space of the system. Thus we associate a locale (which is the topos-theoretical notion of a space and which intrinsically carries the intuitionistic logical structure of a Heyting algebra) to a C*-algebra (which is the noncommutative notion of a space). In this setting, states on A become probability measures (more precisely, valuations) on S(A), and self-adjoint elements of A define continuous functions (more precisely, locale maps) from S(A) to Scott's interval domain. Noting that open subsets of S(A) correspond to propositions about the system, the pairing map that assigns a (generalized) truth value to a state and a proposition assumes an extremely simple categorical form. Formulated in this way, the quantum theory defined by A is essentially turned into a classical theory, internal to the topos T(A).Comment: 52 pages, final version, to appear in Communications in Mathematical Physic

Naked Singularity and Thunderbolt

We consider quantum theoretical effects of the sudden change of the boundary conditions which mimics the occurrence of naked singularities. For a simple demonstration, we study a massless scalar field in $(1 + 1)$-dimensional Minkowski spacetime with finite spatial interval. We calculate the vacuum expectation value of the energy-momentum tensor and explicitly show that singular wave or {\em thunderbolt} appears along the Cauchy horizon. The thunderbolt possibly destroys the Cauchy horizon if its backreaction on the geometry is taken into account, leading to quantum restoration of the global hyperbolicity. The result of the present work may also apply to the situation that a closed string freely oscillating is traveling to a brane and changes itself to an open string pinned-down by the ends satisfying the Dirichlet boundary conditions on the brane.Comment: 12 pages, 1 figure, references added, to appear in Phys. Rev.

Acupuncture is a feasible treatment for post-thoracotomy pain: results of a prospective pilot trial

BACKGROUND: Thoracotomy is associated with severe pain that may persist for years. Acupuncture is a complementary therapy with a proven role in pain control. A randomized trial showed that acupuncture was effective in controlling pain after abdominal surgery, but the efficacy of this technique for the treatment of thoracotomy pain has not been established. We developed a novel technique for convenient application of acupuncture to patients undergoing thoracotomy, and in a Phase II trial evaluated the safety of this intervention and the feasibility of doing a randomized trial. METHODS: Adult patients scheduled for unilateral thoracotomy with preoperative epidural catheter placement received acupuncture immediately prior to surgery. Eighteen semi-permanent intradermal needles were inserted on either side of the spine, and four were inserted in the legs and auricles. Needles were removed after four weeks. Using a numerical rating scale, pain was measured on the first five postoperative days. After discharge, pain was assessed using the Brief Pain Inventory at 7, 30, 60 and 90 days. RESULTS: Thirty-six patients were treated with acupuncture. Of these, 25, 23, and 22 patients provided data at 30, 60, and 90 days, respectively. The intervention was well tolerated by patients with only one minor and transient adverse event of skin ulceration. CONCLUSION: The rate of data completion met our predefined criterion for determining a randomized trial to be feasible (at least 75% of patients tolerated the intervention and provided evaluable data). This novel intervention is acceptable to patients undergoing thoracotomy and does not interfere with standard preoperative care. There was no evidence of important adverse events. We are now testing the hypothesis that acupuncture significantly adds to standard perioperative pain management in a randomized trial

Geophysical anomalies and quartz deformation of the Warburton West structure, central Australia

This paper reports geophysical anomalies and intra-crystalline quartz lamellae in drill cores from the Warburton West Basin overlapping the border of South Australia and the Northern Territory. The pre-Upper Carboniferous ~450×300km-large Warburton Basin, north-eastern South Australia, is marked by distinct eastern and western magnetic, gravity and low-velocity seismic tomography anomalies. Quartz grains from arenite core samples contain intra-crystalline lamellae in carbonate-quartz veins and in clastic grains, similar to those reported earlier from arenites, volcanic rocks and granites from the Warburton East Basin. Universal Stage measurements of quartz lamellae in both sub-basins define Miller-Bravais indices of {10-12} and {10-13}. In-situ quartz lamellae occur only in pre-Late Carboniferous rocks whereas lamellae-bearing clastic quartz grains occur in both pre-Late Carboniferous and post-Late Carboniferous rocks - the latter likely redeposited from the pre-Late Carboniferous basement. Quartz lamellae in clastic quartz grains are mostly curved and bent either due to tectonic deformation or to re-deformation of impact-generated planar features during crustal rebound or/and post-impact tectonic deformation. Seismic tomography low-velocity anomalies in both Warburton West Basin and Warburton East Basin suggest fracturing of the crust to depths of more than 20km. Geophysical modelling of the Cooper Basin, which overlies the eastern Warburton East Basin, suggests existence of a body of high-density (~2.9-3.0gr/cm) and high magnetic susceptibility (SI~0.012-0.037) at a depth of ~6-10km at the centre of the anomalies. In the Warburton West Basin a large magnetic body of SI=0.030 is modelled below ~10km, with a large positive gravity anomaly offset to the north of the magnetic anomaly. In both the Warburton East and Warburton West the deep crustal fracturing suggested by the low velocity seismic tomography complicates interpretations of the gravity data. Universal Stage measurements of quartz lamellae suggest presence of both planar deformation features of shock metamorphic derivation and deformed planar lamella. The latter may be attributed either to re-deformation of impact-generated lamella, impact rebound deformation or/and post impact tectonic deformation. The magnetic anomalies in the Warburton East and West sub-basins are interpreted in terms of (1) presence of deep seated central mafic bodies; (2) deep crustal fracturing and (3) removal of Devonian and Carboniferous strata associated with rebound of a central uplift consequent on large asteroid impact. Further tests of the Warburton structures require deep crustal seismic transects

De-novo transcriptome assembly for gene identification, analysis, annotation, and molecular marker discovery in Onobrychis viciifolia

Background Sainfoin (Onobrychis viciifolia) is a highly nutritious tannin-containing forage legume. In the diet of ruminants sainfoin can have anti-parasitic effects and reduce methane emissions under in vitro conditions. Many of these benefits have been attributed to condensed tannins or proanthocyanidins in sainfoin. A combination of increased use of industrially produced nitrogen fertilizer, issues with establishment and productivity in the first year and more reliable alternatives, such as red clover led to a decline in the use of sainfoin since the middle of the last century. In recent years there has been a resurgence of interest in sainfoin due to its potential beneficial nutraceutical and environmental attributes. However, genomic resources are scarce, thus hampering progress in genetic analysis and improvement. To address this we have used next generation RNA sequencing technology to obtain the first transcriptome of sainfoin. We used the library to identify gene-based simple sequence repeats (SSRs) and potential single nucleotide polymorphisms (SNPs). Results One genotype from each of five sainfoin accessions was sequenced. Paired-end (PE) sequences were generated from cDNA libraries of RNA extracted from 7 day old seedlings. A combined assembly of 92,772 transcripts was produced de novo using the Trinity programme. About 18,000 transcripts were annotated with at least one GO (gene ontology) term. A total of 63 transcripts were annotated as involved in the tannin biosynthesis pathway. We identified 3786 potential SSRs. SNPs were identified by mapping the reads of the individual assemblies against the combined assembly. After stringent filtering a total of 77,000 putative SNPs were identified. A phylogenetic analysis of single copy number genes showed that sainfoin was most closely related to red clover and Medicago truncatula, while Lotus japonicus, bean and soybean are more distant relatives. Conclusions This work describes the first transcriptome assembly in sainfoin. The 92 K transcripts provide a rich source of SNP and SSR polymorphisms for future use in genetic studies of this crop. Annotation of genes involved in the condensed tannin biosynthesis pathway has provided the basis for further studies of the genetic control of this important trait in sainfoin

Curvature singularity of the distributional BTZ black hole geometry

For the non-rotating BTZ black hole, the distributional curvature tensor field is found. It is shown to have singular parts proportional to a $\delta$-distribution with support at the origin. This singularity is related, through Einstein field equations, to a point source. Coordinate invariance and independence on the choice of differentiable structure of the results are addressed.Comment: Latex, 7 page