The use of inhaled corticosteroids in the treatment, of bronchial asthma with particular reference to beclomethasome dipropionate.

MDThe Problem : Corticosteroids may be necessary to control the symptoms of many patients with chronic bronchial asthma, their use, however, is frequently complicated by side effects, which are unpleasant for the patient and often worrying for the physician. Any measure, therefore, which would permit a useful anti-inflammatory effect of these drugs whilst minimising side effects would be of benefit to patients. It is for this reason that, for over twenty years, repeated attempts have been made with every corticosteroid as they have been introduced, to administer them directly onto the bronchial mucous membrane by inhalation in one form or another. These attempts have failed, probably because the steroids used have had potent systemic glucocorticoid effects following any route of administration. The use of inhaled beclomethasone-17,21-dipropionate, however, is in marked contrast to the earlier experiences with inhaled corticosteroids, because the symptoms of bronchial asthma are controlled without important. corticosteroid induced side effects. The aim of this thesis is twofold, first, to establish by simple means, the properties of beclomethasone-17, 21- dipropionate in in an attempt to discover, the reasons why this corticosteroid should be successful when given by inhalation whilst others were not, and secondly, to discover whether the regular use of an inhaled corticosteroid may be complicated by any side effects, peculiar to this route of administration. Summary of the Present Work : The use of corticosteroids in the treatment of bronchial asthma, and, the attempts to reduce side effects by clinical means, including the local, inhaled use of corticosteroids are reviewed. The work of steroid chemists aimed at producing compounds where there may be some separation of antiinflammatory from other glucocorticoid effects is outlined. The literature on inhaled beclomethasone-l7, 2l-dipropionate is reviewed and contrasted with the earlier studies on inhaled corticosteroids. The properties of beclomethasone-17,21-dipropionate in man are investigated. These original studies include an assessment of its topical anti-inflammatory potency on the skin; the effects following its administration by inhalation by mouth, intra-nasally and intravenously on the Hypothalamic-Pituitary-Adrenal (H. P. A. ) axis, together with an investigation of its absorption, and metabolic fate after oral and intravenous administration are described. The effects of beclomethasone-l7,2l0-dipropionate upon circulating white blood cells and fasting blood sugar levels have also been investigated. Particular attention has been paid to describing and reviewing the evidence in animals and in man concerned with potential toxic effects on the tissues of the respiratory tract. The incidence of bacterial infection in the lungs of patients treated with beclomethasone-17,21-dipropionate has also been investigated. Increased colonisation of the oro-phaxynx with candida albicans, and, less frequently, clinical candidiasis is a complication of treatment with beclomethasone-17,21-dipropionate. This, together with possible predisposing factors is assessed. It is concluded : one, that high topical activity together with lower systemic activity and metabolic inactivation of the swallowed portion of beclomethasone-17,2l-dipropionate are the likely reasons why this corticosteroid, in the doses employed, controls bronchial asthma in most patients without causing important glucocorticoid. side effects. And two, although no clinical or experimental evidence exists at present to suggest that this drug is exerting any deleterious effect on the tissues of the respiratory tract, this cannot be excluded and continued vigilance is necessary. Oro-pharyngeal candidiasis is a complication of this treatment, but, at present, the advantages to the patient of reduced or no oral dosage with corticosteroids, outweighs the disadvantages of candidiasis, because this does not occur invariably, it is frequently symptomless, easily treated and has only occurred superficially

Kernel Ellipsoidal Trimming

Ellipsoid estimation is an issue of primary importance in many practical areas such as control, system identification, visual/audio tracking, experimental design, data mining, robust statistics and novelty/outlier detection. This paper presents a new method of kernel information matrix ellipsoid estimation (KIMEE) that finds an ellipsoid in a kernel defined feature space based on a centered information matrix. Although the method is very general and can be applied to many of the aforementioned problems, the main focus in this paper is the problem of novelty or outlier detection associated with fault detection. A simple iterative algorithm based on Titterington's minimum volume ellipsoid method is proposed for practical implementation. The KIMEE method demonstrates very good performance on a set of real-life and simulated datasets compared with support vector machine methods

Missing energy in black hole production and decay at the Large Hadron Collider

Black holes could be produced at the Large Hadron Collider in TeV-scale gravity scenarios. We discuss missing energy mechanisms in black hole production and decay in large extra-dimensional models. In particular, we examine how graviton emission into the bulk could give the black hole enough recoil to leave the brane. Such a perturbation would cause an abrupt termination in Hawking emission and result in large missing-energy signatures.Comment: addressed reviewer comments and updated reference

`NMR Crystallization': in-situ NMR techniques for time-resolved monitoring of crystallization processes

Solid-state NMR spectroscopy is a well-established and versatile technique for studying structural and dynamic properties of solids, and there is considerable potential to exploit the power and versatility of solid-state NMR for in-situ studies of chemical processes. However, a number of technical challenges are associated with adapting this technique for in-situ studies, depending on the process of interest. Recently, an in-situ solid-state NMR strategy for monitoring the evolution of crystallization processes has been developed and has proven to be a promising approach for identifying the sequence of distinct solid forms present as a function of time during crystallization from solution, and for the discovery of new polymorphs. The latest development of this technique, called “CLASSIC” NMR, allows simultaneous measurement of both liquid-state and solid-state NMR spectra as a function of time, thus yielding complementary information on the evolution of both the liquid phase and the solid phase during crystallization from solution. This article gives an overview of the range of NMR strategies that are currently available for in-situ studies of crystallization processes, with examples of applications that highlight the potential of these strategies to deepen our understanding of crystallization phenomena

Hybridization in bottlenose dolphins—A case study of Tursiops aduncus × T. truncatus hybrids and successful backcross hybridization events

The bottlenose dolphin, genus Tursiops is one of the best studied of all the Cetacea with a minimum of two species widely recognised. Common bottlenose dolphins (T. truncatus), are the cetacean species most frequently held in captivity and are known to hybridize with species from at least 6 different genera. In this study, we document several intra-generic hybridization events between T. truncatus and T. aduncus held in captivity. We demonstrate that the F1 hybrids are fertile and can backcross producing apparently healthy offspring, thereby showing introgressive inter-specific hybridization within the genus. We document that female F1 hybrids can reach sexual maturity at 4 yr and 3 mo of age, and can become pregnant and give birth before being fully weaned. The information presented has implications for understanding hybrid reticulation among cetacean species and practical implications for captive facilities housing either Tursiops species or hybrids thereof

Signatures of black holes at the LHC

Signatures of black hole events at CERN's Large Hadron Collider are discussed. Event simulations are carried out with the Fortran Monte Carlo generator CATFISH. Inelasticity effects, exact field emissivities, color and charge conservation, corrections to semiclassical black hole evaporation, gravitational energy loss at formation and possibility of a black hole remnant are included in the analysis.Comment: 13 pages, 7 figure

Superconductivity in the two dimensional Hubbard Model.

Quasiparticle bands of the two-dimensional Hubbard model are calculated using the Roth two-pole approximation to the one particle Green's function. Excellent agreement is obtained with recent Monte Carlo calculations, including an anomalous volume of the Fermi surface near half-filling, which can possibly be explained in terms of a breakdown of Fermi liquid theory. The calculated bands are very flat around the (pi,0) points of the Brillouin zone in agreement with photoemission measurements of cuprate superconductors. With doping there is a shift in spectral weight from the upper band to the lower band. The Roth method is extended to deal with superconductivity within a four-pole approximation allowing electron-hole mixing. It is shown that triplet p-wave pairing never occurs. Singlet d_{x^2-y^2}-wave pairing is strongly favoured and optimal doping occurs when the van Hove singularity, corresponding to the flat band part, lies at the Fermi level. Nearest neighbour antiferromagnetic correlations play an important role in flattening the bands near the Fermi level and in favouring superconductivity. However the mechanism for superconductivity is a local one, in contrast to spin fluctuation exchange models. For reasonable values of the hopping parameter the transition temperature T_c is in the range 10-100K. The optimum doping delta_c lies between 0.14 and 0.25, depending on the ratio U/t. The gap equation has a BCS-like form and (2*Delta_{max})/(kT_c) ~ 4.Comment: REVTeX, 35 pages, including 19 PostScript figures numbered 1a to 11. Uses epsf.sty (included). Everything in uuencoded gz-compressed .tar file, (self-unpacking, see header). Submitted to Phys. Rev. B (24-2-95

Discrimination, labour markets and the Labour Market Prospects of Older Workers: What Can a Legal Case Teach us?

As governments become increasingly concerned about the fiscal implications of the ageing population, labour market policies have sought to encourage mature workers to remain in the labour force. The ‘human capital’ discourses motivating these policies rest on the assumption that older workers armed with motivation and vocational skills will be able to return to fulfilling work. This paper uses the post-redundancy recruitment experiences of former Ansett Airlines flight attendants to develop a critique of these expectations. It suggests that policies to increase older workers’ labour market participation will not succeed while persistent socially constructed age- and gender- typing shape labour demand. The conclusion argues for policies sensitive to the institutional structures that shape employer preferences, the competitive rationality of discriminatory practices, and the irresolvable tension between workers’ human rights and employers’ property rights

In-situ velocity imaging of ultracold atoms using slow--light

The optical response of a moving medium suitably driven into a slow-light propagation regime strongly depends on its velocity. This effect can be used to devise a novel scheme for imaging ultraslow velocity fields. The scheme turns out to be particularly amenable to study in-situ the dynamics of collective and topological excitations of a trapped Bose-Einstein condensate. We illustrate the advantages of using slow-light imaging specifically for sloshing oscillations and bent vortices in a stirred condensate