One evidence base; three stories: do opioids relieve chronic breathlessness?

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. The efficacy of low-dose systemic opioids for chronic breathlessness was questioned by the recent Cochrane review by Barnes et al We examined the reasons for this conflicting finding and re-evaluated the efficacy of systemic opioids. Compared with previous meta-analyses, Barnes et al reported a smaller effect and lower precision, but did not account for matched data of crossover trials (11/12 included trials) and added a risk-of-bias criterion (sample size). When re-analysed to account for crossover data, opioids decreased breathlessness (standardised mean differences -0.32; -0.18 to -0.47; I2=44.8%) representing a clinically meaningful reduction of 0.8 points (0-10 numerical rating scale), consistent across meta-analyses

An Empirical Analysis of the Canadian Term Structure of Zero-Coupon Interest Rates

Zero-coupon interest rates are the fundamental building block of fixed-income mathematics, and as such have an extensive number of applications in both finance and economics. The risk-free government zero-coupon term structure is, however, not directly observable and needs to be generated from the prices of marketable, coupon-bearing bonds. The authors introduce the first public-domain database of constant-maturity zero-coupon yield curves for the Government of Canada bond market. They first outline the mechanics of the curve-fitting algorithm that underlie the model, and then perform some preliminary statistical analysis on the resulting yield curves. The full sample period extends from January 1986 to May 2003; it is broken down into two subsamples, reflecting the structural and macroeconomic changes that impacted the Canadian fixed-income markets over that time. The authors examine the evolution of a number of key interest rates and yield-curve measures over the period, perform a principal-components analysis of the common factors that have influenced yield changes over time, and compare holding-period returns over the sample for assets of various maturities.Financial markets; Interest rates; Econometric and statistical methods

The Kahler Structure of Supersymmetric Holographic RG Flows

We study the metrics on the families of moduli spaces arising from probing with a brane the ten and eleven dimensional supergravity solutions corresponding to renormalisation group flows of supersymmetric large n gauge theory. In comparing the geometry to the physics of the dual gauge theory, it is important to identify appropriate coordinates, and starting with the case of SU(n) gauge theories flowing from N=4 to N=1 via a mass term, we demonstrate that the metric is Kahler, and solve for the Kahler potential everywhere along the flow. We show that the asymptotic form of the Kahler potential, and hence the peculiar conical form of the metric, follows from special properties of the gauge theory. Furthermore, we find the analogous Kahler structure for the N=4 preserving Coulomb branch flows, and for an N=2 flow. In addition, we establish similar properties for two eleven dimensional flow geometries recently presented in the literature, one of which has a deformation of the conifold as its moduli space. In all of these cases, we notice that the Kahler potential appears to satisfy a simple universal differential equation. We prove that this equation arises for all purely Coulomb branch flows dual to both ten and eleven dimensional geometries, and conjecture that the equation holds much more generally.Comment: 26 pages. Late

Induction and repression of mammalian achaete-scute homologue (MASH) gene expression during neuronal differentiation of P19 embryonal carcinoma cells

MASH1 and MASH2, mammalian homologues of the Drosophila neural determination genes achaete-scute, are members of the basic helix-loop-helix (bHLH) family of transcription factors. We show here that murine P19 embryonal carcinoma cells can be used as a model system to study the regulation and function of these genes. MASH1 and MASH2 display complementary patterns of expression during the retinoic-acid-induced neuronal differentiation of P19 cells. MASH1 mRNA is undetectable in undifferentiated P19 cells but is induced to high levels by retinoic acid coincident with neuronal differentiation. In contrast, MASH2 mRNA is expressed in undifferentiated P19 cells and is repressed by retinoic acid treatment. These complementary expression patterns suggest distinct functions for MASH1 and MASH2 in development, despite their sequence homology. In retinoic-acid-treated P19 cells, MASH1 protein expression precedes and then overlaps expression of neuronal markers. However, MASH1 is expressed by a smaller proportion of cells than expresses such markers. MASH1 immunoreactivity is not detected in differentiated cells displaying a neuronal morphology, suggesting that its expression is transient. These features of MASH1 expression are similar to those observed in vivo, and suggest that P19 cells represent a good model system in which to study the regulation of this gene. Forced expression of MASH1 was achieved in undifferentiated P19 cells by transfection of a cDNA expression construct. The transfected cells expressing exogenous MASH1 protein contained E-box-binding activity that could be super-shifted by an anti-MASH1 antibody, but exhibited no detectable phenotypic changes. Thus, unlike myogenic bHLH genes, such as MyoD, which are sufficient to induce muscle differentiation, expression of MASH1 appears insufficient to promote neurogenesis

Optimizing Abstract Abstract Machines

The technique of abstracting abstract machines (AAM) provides a systematic approach for deriving computable approximations of evaluators that are easily proved sound. This article contributes a complementary step-by-step process for subsequently going from a naive analyzer derived under the AAM approach, to an efficient and correct implementation. The end result of the process is a two to three order-of-magnitude improvement over the systematically derived analyzer, making it competitive with hand-optimized implementations that compute fundamentally less precise results.Comment: Proceedings of the International Conference on Functional Programming 2013 (ICFP 2013). Boston, Massachusetts. September, 201

STABILIZATION OF UPLAND RICE PRODUCTION UNDER SHORTENED FALLOW IN WEST AFRICA: RESEARCH PRIORITY SETTING IN A DYNAMIC ENVIRONMENTAL AND ECONOMIC CLIMATE

This paper presents a dynamic model of land resource degradation and shifting rice cultivation in West Africa based upon Boserup and Dvorak. The model indicates the ex ante impact of research strategies to maximize the economic benefits of host plant resistance and land resource management and thereby stabilize yield decline and reduce land degradation.Land Economics/Use, Resource /Energy Economics and Policy,

K-Form Organizations

Contemporary organizations are confronted with increasing challenges in matching their structuraldesigns to the ever increasing flood of information and to the necessity to translate this informationinto actionable knowledge represented in innovations. The progression of organizations from U-forms,or simple unitary functions represented in classic bureaucracies, to M-forms, or multidivisionalstructures with many products often manufactured in many places were both embedded in aone-to-many framework, a top-down approach. However, modern organizations need to develop deeperand deeper tacit understandings that can lead to actionable knowledge that results in innovations andunique strategic advantages. This suggests a need to describe a newly emerging organizational from –the K-form. After detailing its fundamental unit, knowledge spheres, representing the increasingunderstanding from recognition of patterns in matter and energy to information to explicit and tacitknowledge to wisdom, how these spheres interact within a knowledge cube, formed by three dimensionsof domain, access, and function is discussed. Finally, the implications for practice of this approach, theintegration problem, and the importance of visualization are examined. Â