Lifetime cost effectiveness of simvastatin in a range of risk groups and age groups derived from a randomised trial of 20,536 people

<i>Objectives</i>: To evaluate the cost effectiveness of 40 mg simvastatin daily continued for life in people of different ages with differing risks of vascular disease. Design A model developed from a randomised trial was used to estimate lifetime risks of vascular events and costs of treatment and hospital admissions in the United Kingdom. <i>Setting</i>: 69 hospitals in the UK. <i>Participants</i>: 20 536 men and women (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes. <i>Interventions</i>: 40 mg simvastatin daily versus placebo for an average of 5 years. <i>Main</i> <i>outcome</i> <i>measures</i>: Cost effectiveness of 40 mg simvastatin daily expressed as additional cost per life year gained. Major vascular event defined as non-fatal myocardial infarction or death from coronary disease, any stroke, or revascularisation procedure. Results were extrapolated to younger and older age groups at lower risk of vascular disease than were studied directly, as well as to lifetime treatment. <i>Results</i>: At the April 2005 UK price of £4.87 (€7; $9) per 28 day pack of generic 40 mg simvastatin, lifetime treatment was cost saving in most age groups and vascular disease risk groups studied directly. Gains in life expectancy and cost savings decreased with increasing age and with decreasing risk of vascular disease. People aged 40-49 with 5 year risks of major vascular events of 42% and 12% at start of treatment gained 2.49 and 1.67 life years, respectively. Treatment with statins remained cost saving or cost less than £2500 per life year gained in people as young as 35 years or as old as 85 with 5 year risks of a major vascular event as low as 5% at the start of treatment. <i>Conclusions</i>: Treatment with statins is cost effective in a wider population than is routinely treated at present

Travelling waves in a nonlinear degenerate diffusion model for bacterial pattern formation

We study a reaction diffusion model recently proposed in [5] to describe the spatiotemporal evolution of the bacterium Bacillus subtilis on agar plates containing nutrient. An interesting mathematical feature of the model, which is a coupled pair of partial differential equations, is that the bacterial density satisfies a degenerate nonlinear diffusion equation. It was shown numerically that this model can exhibit quasi-one-dimensional constant speed travelling wave solutions. We present an analytic study of the existence and uniqueness problem for constant speed travelling wave solutions. We find that such solutions exist only for speeds greater than some threshold speed giving minimum speed waves which have a sharp profile. For speeds greater than this minimum speed the waves are smooth. We also characterise the dependence of the wave profile on the decay of the front of the initial perturbation in bacterial density. An investigation of the partial differential equation problem establishes,via a global existence and uniqueness argument, that these waves are the only long time solutions supported by the problem. Numerical solutions of the partial differential equation problem are presented and they confirm the results of the analysis

Astrometric signatures of self-gravitating protoplanetary discs

We use high resolution numerical simulations to study whether gravitational instabilities within circumstellar discs can produce astrometrically detectable motion of the central star. For discs with masses of M_disc = 0.1 M_star, which are permanantly stable against fragmentation, we find that the magnitude of the astrometric signal depends upon the efficiency of disc cooling. Short cooling times produce prominent filamentary spiral structures in the disc, and lead to stellar motions that are potentially observable with future high precision astrometric experiments. For a disc that is marginally unstable within radii of \~10 au, we estimate astrometric displacements of 10-100 microarcsec on decade timescales for a star at a distance of 100 pc. The predicted displacement is suppressed by a factor of several in more stable discs in which the cooling time exceeds the local dynamical time by an order of magnitude. We find that the largest contribution comes from material in the outer regions of the disc and hence, in the most pessimistic scenario, the stellar motions caused by the disc could confuse astrometric searches for low mass planets orbiting at large radii. They are, however, unlikely to present any complications in searches for embedded planets orbiting at small radii, relative to the disc size, or Jupiter mass planets or greater orbiting at large radii.Comment: 6 pages, 9 figures, accepted for publication in MNRA

An Analysis of Factors Affecting the Oxygen Consumption of the Isopod Ligia oceanica

This is the publisher's version, also available electronically from http://www.jstor.org/stable/info/30155682A multiple-regression equation was derived in which the statistical significance of the effects of six independent variables on metabolic rate could be arranged in the following order: exposure temperature, body weight, starvation period, feeding period, acclimation temperature, and percentage of lipids. Two multiple-regression equations were required to express the metabolism of Ligia oceanica without loss of accuracy when reapplied to the individual experimental data. One equation accounted for 84% of the variation of metabolism in animals acclimated to 5 or 12 C; the second accounted for 85% of the variation of metabolism in animals acclimated to 18 or 26 C. The rate:temperature curve for aerobic metabolism was sigmoid. A region of reduced temperature sensitivity occurred at intermediate exposure temperatures. Thermal acclimation had little effect on the level of metabolism of well-fed Ligia. The maximum metabolic rate shifted from 27.6 C in fed animals acclimated at 5 C to 28.2 C in those acclimated at 12 C, to 33.1 C in those acclimated at 18 C, and to 33.4 C in those acclimated at 26 C. The region of reduced temperature sensitivity shifted from 15-25 C at low acclimation temperatures to 20-35 C at high acclimation temperatures. The effects of starvation on oxygen consumption are controlled by body size, duration of starvation, and acclimation temperature. Metabolism is suppressed in small animals sooner than large ones at each acclimation temperature; high acclimation temperatures enhance the onset and magnitude of such effects. Exposure temperature and the period of starvation influenced the effect of body size on metabolism

Extrasolar planetary dynamics with a generalized planar Laplace-Lagrange secular theory

The dynamical evolution of nearly half of the known extrasolar planets in multiple-planet systems may be dominated by secular perturbations. The commonly high eccentricities of the planetary orbits calls into question the utility of the traditional Laplace-Lagrange (LL) secular theory in analyses of the motion. We analytically generalize this theory to fourth-order in the eccentricities, compare the result with the second-order theory and octupole-level theory, and apply these theories to the likely secularly-dominated HD 12661, HD 168443, HD 38529 and Ups And multi-planet systems. The fourth-order scheme yields a multiply-branched criterion for maintaining apsidal libration, and implies that the apsidal rate of a small body is a function of its initial eccentricity, dependencies which are absent from the traditional theory. Numerical results indicate that the primary difference the second and fourth-order theories reveal is an alteration in secular periodicities, and to a smaller extent amplitudes of the planetary eccentricity variation. Comparison with numerical integrations indicates that the improvement afforded by the fourth-order theory over the second-order theory sometimes dwarfs the improvement needed to reproduce the actual dynamical evolution. We conclude that LL secular theory, to any order, generally represents a poor barometer for predicting secular dynamics in extrasolar planetary systems, but does embody a useful tool for extracting an accurate long-term dynamical description of systems with small bodies and/or near-circular orbits.Comment: 14 pages, 12 figures, 1 table, accepted for publication in Ap