Regularity of Infinity for Elliptic Equations with Measurable Coefficients and Its Consequences

This paper introduces a notion of regularity (or irregularity) of the point at infinity for the unbounded open subset of \rr^{N} concerning second order uniformly elliptic equations with bounded and measurable coefficients, according as whether the A-harmonic measure of the point at infinity is zero (or positive). A necessary and sufficient condition for the existence of a unique bounded solution to the Dirichlet problem in an arbitrary open set of \rr^{N}, N\ge 3 is established in terms of the Wiener test for the regularity of the point at infinity. It coincides with the Wiener test for the regularity of the point at infinity in the case of Laplace equation. From the topological point of view, the Wiener test at infinity presents thinness criteria of sets near infinity in fine topology. Precisely, the open set is a deleted neigborhood of the point at infinity in fine topology if and only if infinity is irregular.Comment: 20 page

Kleene Algebras and Semimodules for Energy Problems

With the purpose of unifying a number of approaches to energy problems found in the literature, we introduce generalized energy automata. These are finite automata whose edges are labeled with energy functions that define how energy levels evolve during transitions. Uncovering a close connection between energy problems and reachability and B\"uchi acceptance for semiring-weighted automata, we show that these generalized energy problems are decidable. We also provide complexity results for important special cases

Simulations of Weighted Tree Automata

Simulations of weighted tree automata (wta) are considered. It is shown how such simulations can be decomposed into simpler functional and dual functional simulations also called forward and backward simulations. In addition, it is shown in several cases (fields, commutative rings, Noetherian semirings, semiring of natural numbers) that all equivalent wta M and N can be joined by a finite chain of simulations. More precisely, in all mentioned cases there exists a single wta that simulates both M and N. Those results immediately yield decidability of equivalence provided that the semiring is finitely (and effectively) presented.Comment: 17 pages, 2 figure

Blooming Artifact Reduction in Coronary Artery Calcification by A New De-blooming Algorithm: Initial Study

The aim of this study was to investigate the use of de-blooming algorithm in coronary CT angiography (CCTA) for optimal evaluation of calcified plaques. Calcified plaques were simulated on a coronary vessel phantom and a cardiac motion phantom. Two convolution kernels, standard (STND) and high-definition standard (HD STND), were used for imaging reconstruction. A dedicated de-blooming algorithm was used for imaging processing. We found a smaller bias towards measurement of stenosis using the deblooming algorithm (STND: bias 24.6% vs 15.0%, range 10.2% to 39.0% vs 4.0% to 25.9%; HD STND: bias 17.9% vs 11.0%, range 8.9% to 30.6% vs 0.5% to 21.5%). With use of de-blooming algorithm, specificity for diagnosing significant stenosis increased from 45.8% to 75.0% (STND), from 62.5% to 83.3% (HD STND); while positive predictive value (PPV) increased from 69.8% to 83.3% (STND), from 76.9% to 88.2% (HD STND). In the patient group, reduction in calcification volume was 48.1 ± 10.3%, reduction in coronary diameter stenosis over calcified plaque was 52.4 ± 24.2%. Our results suggest that the novel de-blooming algorithm could effectively decrease the blooming artifacts caused by coronary calcified plaques, and consequently improve diagnostic accuracy of CCTA in assessing coronary stenosis

Experience of safety monitoring in the context of a prospective observational study of artemether-lumefantrine in rural Tanzania: lessons learned for pharmacovigilance reporting

<p>Abstract</p> <p>Objectives</p> <p>To identify and implement strategies that help meet safety monitoring requirements in the context of an observational study for artemether-lumefantrine (AL) administered as first-line treatment for uncomplicated malaria in rural Tanzania.</p> <p>Methods</p> <p>Pharmacovigilance procedures were developed through collaboration between the investigating bodies, the relevant regulatory authority and the manufacturer of AL. Training and refresher sessions on the pharmacovigilance system were provided for healthcare workers from local health facilities and field recorders of the Ifakara Health Demographic Surveillance System (IHDSS). Three distinct channels for identification of adverse events (AEs) and serious adverse events (SAEs) were identified and implemented. Passive reporting took place through IHDSS and health care facilities, starting in October 2007. The third channel was through solicited reporting that was included in the context of a survey on AL as part of the ALIVE (<b>A</b>rtemether-<b>L</b>umefantrine <b>I</b>n <b>V</b>ulnerable patients: <b>E</b>xploring health impact) study (conducted only in March-April 2008).</p> <p>Results</p> <p>Training was provided for 40 healthcare providers (with refresher training 18 months later) and for six field recorders. During the period 1^stSeptember 2007 to 31^stMarch 2010, 67 AEs were reported including 52 under AL, five under sulphadoxine-pyrimethamine, one under metakelfin, two after antibiotics; the remaining seven were due to anti-pyretic or anti-parasite medications. Twenty patients experienced SAEs; in 16 cases, a relation to AL was suspected. Six of the 20 cases were reported within 24 hours of occurrence.</p> <p>Discussion</p> <p>Safety monitoring and reporting is possible even in settings with weak health infrastructure. Reporting can be enhanced by regular and appropriate training of healthcare providers. SMS text alerts provide a practical solution to communication challenges.</p> <p>Conclusion</p> <p>Experience gained in this setting could help to improve spontaneous reporting of AEs and SAEs to health authorities or marketing authorization holders.</p

Ongoing challenges in the management of malaria

This article gives an overview of some of the ongoing challenges that are faced in the prevention, diagnosis and treatment of malaria

Intravenous pharmacokinetics, oral bioavailability, dose proportionality and in situ permeability of anti-malarial lumefantrine in rats

<p>Abstract</p> <p>Background</p> <p>Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats.</p> <p>Methods</p> <p>A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. <it>In-situ </it>permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC.</p> <p>Results</p> <p>For nominal doses increasing in a 1:2:4 proportion, the C_maxand AUC_0-∞values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the C_maxand the AUC_0-tvalues for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10^-5cm/s) in permeability study.</p> <p>Conclusions</p> <p>The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the <it>in-situ </it>permeability study.</p