Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms

Optimal designs for composed models in pharmacokinetic-pharmacodynamic experiments

We discuss design issues for pharmacokinetic and pharmacodynamic (PK/PD) models and provide closed form descriptions for locally optimal designs for estimating individual parameter in two frequently used models. We propose standardized maximin optimal designs that remove dependence on the particular parameter of interest by maximizing the minimal efficiency across all parameters. Further, robust designs are proposed to overcome the dependence on the parameters of interest and the nominal values of the parameters. We compare performance of these optimal designs with designs used in four real studies from the pharmacokinetic/pharmacodynamic literature and show that our proposed designs provide definite advantages over those used in practice

Optimal designs for discriminating dose response models in toxicology studies

We consider design issues for toxicology studies when we have a continuous response but the true mean response is only known to be a member in a class of nested models. This class of models were proposed by toxicologists who were concerned with only estimation problems. We develop robust and effcient designs for model discrimination and optimal designs for estimating parameters in the selected model at the same time. In particular, we propose designs that maximize the minimum of D- or D_1-efficiencies over all models in the given class. We show that these optimal designs are efficient for determining an appropriate model from the postulated class, quite efficient for estimating model parameters in the identified model and also robust with respect to model mis-specification. To facilitate use of these designs in practice, we have also constructed a web site to enable practitioners to generate optimal designs for their problems

Risk estimators for choosing regularization parameters in ill-posed problems - Properties and limitations

This paper discusses the properties of certain risk estimators that recently regained popularity for choosing regularization parameters in ill-posed problems, in particular for sparsity regularization. They apply Stein’s unbiased risk estimator (SURE) to estimate the risk in either the space of the unknown variables or in the data space. We will call the latter PSURE in order to distinguish the two different risk functions. It seems intuitive that SURE is more appropriate for ill-posed problems, since the properties in the data space do not tell much about the quality of the reconstruction. We provide theoretical studies of both approaches for linear Tikhonov regularization in a finite dimensional setting and estimate the quality of the risk estimators, which also leads to asymptotic convergence results as the dimension of the problem tends to infinity. Unlike previous works which studied single realizations of image processing problems with a very low degree of ill-posedness, we are interested in the statistical behaviour of the risk estimators for increasing ill-posedness. Interestingly, our theoretical results indicate that the quality of the SURE risk can deteriorate asymptotically for ill-posed problems, which is confirmed by an extensive numerical study. The latter shows that in many cases the SURE estimator leads to extremely small regularization parameters, which obviously cannot stabilize the reconstruction. Similar but less severe issues with respect to robustness also appear for the PSURE estimator, which in comparison to the rather conservative discrepancy principle leads to the conclusion that regularization parameter choice based on unbiased risk estimation is not a reliable procedure for ill-posed problems. A similar numerical study for sparsity regularization demonstrates that the same issue appears in non-linear variational regularization approaches

Strong asymptotics for Jacobi polynomials with varying nonstandard parameters

Strong asymptotics on the whole complex plane of a sequence of monic Jacobi polynomials $P_n^{(\alpha_n, \beta_n)}$ is studied, assuming that $$\lim_{n\to\infty} \frac{\alpha_n}{n}=A, \qquad \lim_{n\to\infty} \frac{\beta _n}{n}=B,$$ with $A$ and $B$ satisfying $A > -1$, $B>-1$, $A+B < -1$. The asymptotic analysis is based on the non-Hermitian orthogonality of these polynomials, and uses the Deift/Zhou steepest descent analysis for matrix Riemann-Hilbert problems. As a corollary, asymptotic zero behavior is derived. We show that in a generic case the zeros distribute on the set of critical trajectories $\Gamma$ of a certain quadratic differential according to the equilibrium measure on $\Gamma$ in an external field. However, when either $\alpha_n$, $\beta_n$ or $\alpha_n+\beta_n$ are geometrically close to $\Z$, part of the zeros accumulate along a different trajectory of the same quadratic differential.Comment: 31 pages, 12 figures. Some references added. To appear in Journal D'Analyse Mathematiqu

The quest for companions to post-common envelope binaries: I. Searching a sample of stars from the CSS and SDSS

As part of an ongoing collaboration between student groups at high schools and professional astronomers, we have searched for the presence of circum-binary planets in a bona-fide unbiased sample of twelve post-common envelope binaries (PCEBs) from the Catalina Sky Survey (CSS) and the Sloan Digital Sky Survey (SDSS). Although the present ephemerides are significantly more accurate than previous ones, we find no clear evidence for orbital period variations between 2005 and 2011 or during the 2011 observing season. The sparse long-term coverage still permits O-C variations with a period of years and an amplitude of tens of seconds, as found in other systems. Our observations provide the basis for future inferences about the frequency with which planet-sized or brown-dwarf companions have either formed in these evolved systems or survived the common envelope (CE) phase.Comment: accepted by A&

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13