We study differential cohomology on categories of globally hyperbolic Lorentzian manifolds. The Lorentzian metric allows us to define a natural transformation whose kernel generalizes Maxwell's equations and fits into a restriction of the fundamental exact sequences of differential cohomology. We consider smooth Pontryagin duals of differential cohomology groups, which are subgroups of the character groups. We prove that these groups fit into smooth duals of the fundamental exact sequences of differential cohomology and equip them with a natural presymplectic structure derived from a generalized Maxwell Lagrangian. The resulting presymplectic Abelian groups are quantized using the CCR-functor, which yields a covariant functor from our categories of globally hyperbolic Lorentzian manifolds to the category of C∗-algebras. We prove that this functor satisfies the causality and time-slice axioms of locally covariant quantum field theory, but that it violates the locality axiom. We show that this violation is precisely due to the fact that our functor has topological subfunctors describing the Pontryagin duals of certain singular cohomology groups. As a byproduct, we develop a Fréchet–Lie group structure on differential cohomology groups.

We show a connection between the CDE′ inequality introduced in Horn et al. (Volume doubling, Poincaré inequality and Gaussian heat kernel estimate for nonnegative curvature graphs. arXiv:1411.5087v2, 2014) and the CDψ inequality established in Münch (Li–Yau inequality on finite graphs via non-linear curvature dimension conditions. arXiv:1412.3340v1, 2014). In particular, we introduce a CDφψ inequality as a slight generalization of CDψ which turns out to be equivalent to CDE′ with appropriate choices of φ and ψ. We use this to prove that the CDE′ inequality implies the classical CD inequality on graphs, and that the CDE′ inequality with curvature bound zero holds on Ricci-flat graphs.

Background: Infliximab (IFX), an anti-TNF monoclonal antibody approved for the treatment of inflammatory bowel disease, is dosed per kg body weight (BW). However, the rationale for body size adjustment has not been unequivocally demonstrated [1], and first attempts to improve IFX therapy have been undertaken [2]. The aim of our study was to assess the impact of different dosing strategies (i.e. body size-adjusted and fixed dosing) on drug exposure and pharmacokinetic (PK) target attainment. For this purpose, a comprehensive simulation study was performed, using patient characteristics (n=116) from an in-house clinical database. Methods: IFX concentration-time profiles of 1000 virtual, clinically representative patients were generated using a previously published PK model for IFX in patients with Crohn's disease [3]. For each patient 1000 profiles accounting for PK variability were considered. The IFX exposure during maintenance treatment after the following dosing strategies was compared: i) fixed dose, and per ii) BW, iii) lean BW (LBW), iv) body surface area (BSA), v) height (HT), vi) body mass index (BMI) and vii) fat-free mass (FFM)). For each dosing strategy the variability in maximum concentration Cmax, minimum concentration Cmin (= C8weeks) and area under the concentration-time curve (AUC), as well as percent of patients achieving the PK target, Cmin=3 μg/mL [4] were assessed. Results: For all dosing strategies the variability of Cmin (CV ≈110%) was highest, compared to Cmax and AUC, and was of similar extent regardless of dosing strategy. The proportion of patients reaching the PK target (≈⅓ was approximately equal for all dosing strategies.

We study biased Maker-Breaker positional games between two players, one of whom is playing randomly against an opponent with an optimal strategy. In this work we focus on the case of Breaker playing randomly and Maker being "clever". The reverse scenario is treated in a separate paper. We determine the sharp threshold bias of classical games played on the edge set of the complete graph , such as connectivity, perfect matching, Hamiltonicity, and minimum degree-1 and -2. In all of these games, the threshold is equal to the trivial upper bound implied by the number of edges needed for Maker to occupy a winning set. Moreover, we show that CleverMaker can not only win against asymptotically optimal bias, but can do so very fast, wasting only logarithmically many moves (while the winning set sizes are linear in n).

The paper develops some crucial steps in extending the first-order cone or edge calculus to higher singularity orders. We focus here on order 2, but the ideas are motivated by an iterative approach for higher singularities.