The admissibility domain of rarefaction shock waves in the near-critical vapour-liquid equilibrium region of pure typical fluids

Application of the scaled fundamental equation of state of Balfour et al. (Phys. Lett. A, vol. 65, 1978, pp. 223-225) based upon universal critical exponents, demonstrates that there exists a bounded thermodynamic domain, located within the vapour-liquid equilibrium region and close to the critical point, featuring so-called negative nonlinearity. As a consequence, rarefaction shock waves with phase transition are physically admissible in a limited two-phase region in the close proximity of the liquid-vapour critical point. The boundaries of the admissibility region of rarefaction shock waves are identified from first-principle conservation laws governing compressible flows, complemented with the scaled fundamental equations. The exemplary substances considered here are methane, ethylene and carbon dioxide. Nonetheless, the results are arguably valid in the near-critical state of any common fluid, namely any fluid whose molecular interactions are governed by short-range forces conforming to three-dimensional Ising-like systems, including, e.g. water. Computed results yield experimentally feasible admissible rarefaction shock waves generating a drop in pressure from 1 to 6 bar and pre-shock Mach numbers exceeding 1.5

Towards an analytical description of active microswimmers in clean and in surfactant-covered drops

Geometric confinements are frequently encountered in the biological world and strongly affect the stability, topology, and transport properties of active suspensions in viscous flow. Based on a far-field analytical model, the low-Reynolds-number locomotion of a self-propelled microswimmer moving inside a clean viscous drop or a drop covered with a homogeneously distributed surfactant, is theoretically examined. The interfacial viscous stresses induced by the surfactant are described by the well-established Boussinesq-Scriven constitutive rheological model. Moreover, the active agent is represented by a force dipole and the resulting fluid-mediated hydrodynamic couplings between the swimmer and the confining drop are investigated. We find that the presence of the surfactant significantly alters the dynamics of the encapsulated swimmer by enhancing its reorientation. Exact solutions for the velocity images for the Stokeslet and dipolar flow singularities inside the drop are introduced and expressed in terms of infinite series of harmonic components. Our results offer useful insights into guiding principles for the control of confined active matter systems and support the objective of utilizing synthetic microswimmers to drive drops for targeted drug delivery applications.Comment: 19 pages, 7 figures. Regular article contributed to the Topical Issue of the European Physical Journal E entitled "Physics of Motile Active Matter" edited by Gerhard Gompper, Clemens Bechinger, Holger Stark, and Roland G. Winkle

Oscillatory surface rheotaxis of swimming E. coli bacteria

Bacterial contamination of biological conducts, catheters or water resources is a major threat to public health and can be amplified by the ability of bacteria to swim upstream. The mechanisms of this rheotaxis, the reorientation with respect to flow gradients, often in complex and confined environments, are still poorly understood. Here, we follow individual E. coli bacteria swimming at surfaces under shear flow with two complementary experimental assays, based on 3D Lagrangian tracking and fluorescent flagellar labelling and we develop a theoretical model for their rheotactic motion. Three transitions are identified with increasing shear rate: Above a first critical shear rate, bacteria shift to swimming upstream. After a second threshold, we report the discovery of an oscillatory rheotaxis. Beyond a third transition, we further observe coexistence of rheotaxis along the positive and negative vorticity directions. A full theoretical analysis explains these regimes and predicts the corresponding critical shear rates. The predicted transitions as well as the oscillation dynamics are in good agreement with experimental observations. Our results shed new light on bacterial transport and reveal new strategies for contamination prevention.Comment: 12 pages, 5 figure

Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38

We have shown previously that the terminal disposition half-life of SN-38, the active metabolite of irinotecan, is much longer than earlier thought. Currently, it is not known whether this prolonged exposure has any relevance toward SN-38-induced toxicity. Here, we found that SN-38 concentrations present in human plasma for up to 3 weeks after a single irinotecan infusion induce significant cytotoxicity in vitro. Using pharmacokinetic data from 26 patients, with sampling up to 500 h, relationships were evaluated between systemic exposure (AUC) to SN-38 and the per cent decrease in absolute neutrophil count (ANC) at nadir, or by taking the entire time course of ANC into account (AOC). The time course of SN-38 concentrations (AUC500 h) was significantly related to this AOC (P<0.001). Based on these findings, a new limited-sampling model was developed for SN-38 AUC500 h using only two timed samples: AUC500 h=(6.588×C2.5 h)+(146.4×C49.5 h)+15.53, where C2.5 h and C49.5 h are plasma concentrations at 2.5 and 49.5 h after start of infusion, respectively. The use of this limited-sampling model may open up historic databases to retrospectively obtain information about SN-38-induced toxicity in patients treated with irinotecan

The ambiguity of human ashes: exploring encounters with cremated remains in the Netherlands

This article explores cremation and disposal practices in the Netherlands, focusing on the attitudes and experiences of bereaved Dutch people in relation to cremated remains. In academic and professional narratives, human ashes are commonly described as “important,” as “sacred,” and as a vehicle to continue intense and physical relationships with the dead. Based on quantitative and qualitative data this article illustrates the ambiguity of such relationships. It highlights the diverse experiences, unexpected challenges, and moral obligations that can be evoked by the deceased’s ashes, where the latter are seen as embedded in material practices and entangled in social relationships

Applying a cost-based pricing model for innovative cancer treatments subject to indication expansion:A case study for pembrolizumab and daratumumab

BACKGROUND: Expanding the indication of already approved immuno-oncology drugs presents treatment opportunities for patients but also strains healthcare systems. Cost-based pricing models are discussed as a possibility for cost containment. This study focuses on two drugs, pembrolizumab (Keytruda) and daratumumab (Darzalex), to explore the potential effect of indication broadening on the estimated price when using the cost-based pricing (CBP) model proposed by Uyl-de Groot and Löwenberg (2018). METHODS: The model was used to calculate cumulative yearly prices, cumulative prices per indication, and non-cumulative indication-based prices using inputs such as research and development (R&amp;D) costs, manufacturing costs, eligible patient population, and a profit margin. A deterministic stepwise analysis and scenario analysis were conducted to examine how sensitive the estimated price is to the different input assumptions. RESULTS: The yearly cumulative cost-based prices (CBPs) ranged from €52 to €885 for pembrolizumab per vial and €823 to €31,941 for daratumumab per vial. Prices were higher in initial years or indications due to smaller patient populations, decreased over time or after additional indications. Sensitivity analysis showed that the number of eligible patients had the most significant impact on the estimated price. In the scenario analysis the profit margin contributed most to a higher CBPs for both drugs. Lower estimates resulted from assumed lower R&amp;D costs. DISCUSSION: The estimated CBPs are consistently lower than Dutch list prices for pembrolizumab (€2,861), mainly resulting from larger patient populations in registered indications. However, daratumumab's list prices fall within the range of modeled CBPs depending on the year or indication (€4,766). Both CBPs decrease over time or with additional indications. The number of eligible patients and initial R&amp;D costs have the most significant influence on the CBPs. These findings contribute to the ongoing discussions on pharmaceutical pricing, especially concerning cancer drugs with expanding indications.</p

Potential merits for space robotics from novel concepts of actuation for soft robotics

Autonomous robots in dynamic and unstructured environments require high performance, energy efficient and reliable actuators. In this paper we give an overview of the first results of two lines of research regarding the novel actuation principle we introduced: Series-Parallel Elastic Actuation (SPEA). Firstly, we introduce the SPEA concept and present first prototypes and results. Secondly, we discuss the potential of self-healing materials in robotics, and discuss the results on the first self-healing pneumatic cell and selfhealing mechanical fuse. Both concepts have the potential to improve performance, energy efficiency and reliability