Institut für Mathematik
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Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis alpha monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting.
We construct eta- and rho-invariants for Dirac operators, on the universal covering of a closed manifold, that are invariant under the projective action associated to a 2-cocycle of the fundamental group. We prove an Atiyah-Patodi-Singer index theorem in this setting, as well as its higher generalisation. Applications concern the classification of positive scalar curvature metrics on closed spin manifolds. We also investigate the properties of these twisted invariants for the signature operator and the relation to the higher invariants.
The evolution of the closed Friedmann Universe with a packet of short scalar waves is considered with the help of the Wheeler-DeWitt equation. The packet ensures conservation of homogeneity and isotropy of the metric on average. It is shown that during tunneling the amplitudes of short waves of a scalar field can increase catastrophically promptly if their influence to the metric is not taken into account. This effect is similar to the Rubakov-effect of catastrophic particle creation calculated already in 1984. In our approach to the problem it is possible to consider a self- consistent dynamics of the expansion of the Universe and amplification of short waves. It results in a decrease of the barrier and interruption of amplification of waves, and we get an exit of the wave function from the quantum to the classically available region.