The effect of weight, body mass index, age, sex, and race on plasma concentrations of subcutaneous sumatriptan: a pooled analysis.

Objective/backgroundFactors such as body size (weight and body mass index [BMI]), age, sex, and race might influence the clinical response to sumatriptan. We evaluated the impact of these covariates on the plasma concentration (Cp) profile of sumatriptan administered subcutaneously.MethodsWe conducted three pharmacokinetic studies of subcutaneous sumatriptan in 98 healthy adults. Sumatriptan was administered subcutaneously (236 administrations) as either DFN-11 3 mg, a novel 0.5 mL autoinjector being developed by Dr. Reddy's Laboratories; Imitrex(®) (Sumatriptan) injection 3 mg or 6 mg (6 mg/0.5 mL); or Imitrex STATdose 4 mg or 6 mg (0.5 mL). Blood was sampled for 12 hours to determine sumatriptan Cp. Maximum Cp (Cmax), area under the curve during the first 2 hours (AUC0-2), and total area under the curve (AUC0-∞) were determined using noncompartmental methods. Post hoc analyses were conducted to determine the relationship between these exposure metrics and each of body weight, BMI, age, sex, and race (categorized as white, black, or others).ResultsBoth weight and BMI correlated negatively with each exposure metric for each treatment group. Across all treatment groups, AUC0-2 for subjects with BMI less than or equal to median value was 1.03-1.12 times the value for subjects with BMI more than median value. For subjects with BMI less than or equal to median value receiving DFN-11, median AUC0-2 was slightly less than that for subjects with BMI more than median value receiving Imitrex 4 mg and larger than that for subjects with BMI more than median value receiving Imitrex 3 mg. Results were similar for the other exposure metrics and for weight. Exposure was higher in women than in men, which can be attributed in part to differences in weight. There was no relationship between exposure and age. For DFN-11, AUC0-2 and AUC0-∞ were lower in nonwhites compared with whites; the ratio of median values was 0.84 and 0.89, respectively. A similar, nonstatistically significant, trend was observed in the other products (ratio of median values ranging from 0.84 to 0.89).ConclusionWeight and BMI appear to be important covariates for sumatriptan exposure: subjects with lower values for either metric of body size have higher systemic exposure compared with subjects with higher values. Additional studies are required to determine if doses of subcutaneous sumatriptan may be adjusted based on BMI for comparable efficacy and a potentially improved tolerability profile

Agent Based Approaches to Engineering Autonomous Space Software

Current approaches to the engineering of space software such as satellite control systems are based around the development of feedback controllers using packages such as MatLab's Simulink toolbox. These provide powerful tools for engineering real time systems that adapt to changes in the environment but are limited when the controller itself needs to be adapted. We are investigating ways in which ideas from temporal logics and agent programming can be integrated with the use of such control systems to provide a more powerful layer of autonomous decision making. This paper will discuss our initial approaches to the engineering of such systems.Comment: 3 pages, 1 Figure, Formal Methods in Aerospac

Method for defect free keyhole plasma arc welding

A plasma arc welding process for welding metal of increased thickness with one pass includes operating the plasma arc welding apparatus at a selected plasma gas flow rate, travel speed and arc current, to form a weld having a penetration ratio to weld height to weld width, and maintaining the penetration ratio at less than 0.74. Parameters for the plasma gas flow rate, travel speed and arc current are adjusted to a steady state condition during a start up period and maintained during the steady state condition to complete a weld. During a terminal stopping period, the travel speed is stopped and instantaneously replaced by filler wire which adds material to fill the keyhole that had been formed by the welding process. Parameters are subsequently adjusted during the stopping period to terminate the weld in a sound manner

Formal Verification of Autonomous Vehicle Platooning

The coordination of multiple autonomous vehicles into convoys or platoons is expected on our highways in the near future. However, before such platoons can be deployed, the new autonomous behaviors of the vehicles in these platoons must be certified. An appropriate representation for vehicle platooning is as a multi-agent system in which each agent captures the "autonomous decisions" carried out by each vehicle. In order to ensure that these autonomous decision-making agents in vehicle platoons never violate safety requirements, we use formal verification. However, as the formal verification technique used to verify the agent code does not scale to the full system and as the global verification technique does not capture the essential verification of autonomous behavior, we use a combination of the two approaches. This mixed strategy allows us to verify safety requirements not only of a model of the system, but of the actual agent code used to program the autonomous vehicles

Measure Transport with Kernel Stein Discrepancy

Measure transport underpins several recent algorithms for posterior approximation in the Bayesian context, wherein a transport map is sought to minimise the Kullback--Leibler divergence (KLD) from the posterior to the approximation. The KLD is a strong mode of convergence, requiring absolute continuity of measures and placing restrictions on which transport maps can be permitted. Here we propose to minimise a kernel Stein discrepancy (KSD) instead, requiring only that the set of transport maps is dense in an $L^2$ sense and demonstrating how this condition can be validated. The consistency of the associated posterior approximation is established and empirical results suggest that KSD is competitive and more flexible alternative to KLD for measure transport

Reconfigurable Autonomy

This position paper describes ongoing work at the Universities of Liverpool, Sheffield and Surrey in the UK on developing hybrid agent architectures for controlling autonomous systems, and specifically for ensuring that agent-controlled dynamic reconfiguration is viable. The work outlined here forms part of the Reconfigurable Autonomy research project

Agent-based autonomous systems and abstraction engines: Theory meets practice

We report on experiences in the development of hybrid autonomous systems where high-level decisions are made by a rational agent. This rational agent interacts with other sub-systems via an abstraction engine. We describe three systems we have developed using the EASS BDI agent programming language and framework which supports this architecture. As a result of these experiences we recommend changes to the theoretical operational semantics that underpins the EASS framework and present a fourth implementation using the new semantics

Relationship between non-thermal electron energy spectra and GOES classes

We investigate the influence of the variations of energy spectrum of non-thermal electrons on the resulting GOES classes of solar flares. Twelve observed flares with various soft to hard X-ray emission ratios were modelled using different non-thermal electron energy distributions. Initial values of the flare physical parameters including geometrical properties were estimated using observations. We found that, for a fixed total energy of non-thermal electrons in a flare, the resulting GOES class of the flare can be changed significantly by varying the spectral index and low energy cut-off of the non-thermal electron distribution. Thus, the GOES class of a flare depends not only on the total non-thermal electrons energy but also on the electron beam parameters. For example, we were able to convert a M2.7 class solar flare into a merely C1.4 class one and a B8.1 class event into a C2.6 class flare. The results of our work also suggest that the level of correlation between the cumulative time integral of HXR and SXR fluxes can depend on the considered HXR energy range.Comment: 8 pages, 5 figures, Astronomy and Astrophysics (accepted, March 2009

Shaken and stirred: conduction and turbulence in clusters of galaxies

(abridged) Uninhibited radiative cooling in clusters of galaxies would lead to excessive mass accretion rates contrary to observations. One of the key proposals to offset radiative energy losses is thermal conduction from outer, hotter layers of cool core clusters to their centers. However, conduction is sensitive to magnetic field topology. In cool-core clusters the heat buoyancy instability (HBI) leads to B-fields ordered preferentially in the direction perpendicular to that of gravity, which significantly reduces the level of conduction below the classical Spitzer-Braginskii value. However, the cluster cool cores are rarely in perfect hydrostatic equilibrium. Sloshing motions due to minor mergers, galaxy motions or AGN can significantly perturb the gas and affect the level of thermal conduction. We perform 3D AMR MHD simulations of the effect of turbulence on the properties of the anisotropic thermal conduction in cool core clusters. We show that very weak subsonic motions, well within observational constraints, can randomize the magnetic field and significantly boost effective thermal conduction beyond the saturated values expected in the pure unperturbed HBI case. We find that the turbulent motions can essentially restore the conductive heat flow to the cool core to level comparable to the theoretical maximum of 1/3 Spitzer for a highly tangled field. Runs with radiative cooling show that the cooling catastrophe can be averted and the cluster core stabilized. Above a critical Froude number, these same turbulent motions also eliminate the tangential bias in the velocity and magnetic field that is otherwise induced by the trapped g-modes. Our results can be tested with future radio polarization measurements, and have implications for efficient metal dispersal in clusters.Comment: submitted to ApJ, references added, expanded Section