The influence of coagulation system on early leukocyte recruitment and acute microcirculatory injury after extended hepatectomy

Das hepatektomie-induzierte Leberversagen ist ein potentiell tödliches Krankheitsbild nach erweiterter Leberresektion oder Leberteiltransplantation. Dieses Versagen scheint einerseits durch eine supraphysiologische Belastung der Restleber, andererseits durch die hyperperfusionsbedingten Mikrozirkulationsverletzungen und eine verhinderte Leberregeneration verursacht zu werden. Der genaue pathophysiologische Mechanismus der mikrovaskulären Schädigung in der akuten Phase konnte jedoch bisher noch nicht entschlüsselt werden. Im Rahmen der vorliegenden Doktorarbeit wurden die Einflüsse der wichtigen Bestandteile der Koagulationskaskade bei akuter Leberschädigung nach partieller Hepatektomie mittels intravitalmikroskopischer Methoden sowie weiterführender laborchemischer Untersuchungen und (immun-)histochemischer Aufarbeitung der Leberpräparate untersucht. Zuerst wurde ein Mausmodell für die intravitalmikroskopische Untersuchung etabliert. Nach erweiterter Hepatektomie wurde neben einer Perfusionsstörung eine ausgeprägte Endothel- Leukozyten-Interaktion beobachtet. Die Serinproteasen beeinflussten sowohl die Mikroperfusion wie auch die Leberschädigung durch eine frühe Leukozytenrekrutierung nach partieller Hepatektomie. Mittels eines Thrombozytendepletionsmodells wurde der Einfluss der Thrombozyten nach erweiterter Hepatektomie untersucht. Die Ergebnisse deuteten darauf hin, dass Thrombozyten die Rekrutierung der verschiedenen Leukozytensubpopulationen durch eine ICAM-1-abhängige Endothel-Leukozyten-Interaktion regulierten. Zudem führte die Depletion der Thrombozyten zu einer signifikant verminderten Verschlechterung der Leberfunktion. Infolgedessen wurde die Rolle des PAR-4, ein Aktivator der Thrombozyten, in der Bildung von Mikrothrombosen als Ursache der Perfusionsstörung nach partieller Hepatektomie mithilfe der Zwei-Photon-Mikroskopie untersucht. Die Thrombozytenaktivierung über PAR-4 induzierte Mikrothrombosen und vermehrte Neutrophil-Thrombozyten-Interaktionen in hepatischen Sinusoiden, wodurch eine Akutleberschädigung nach partieller Hepatektomie verschlimmert wurde. Schlussendlich wurde die Fibrinogenbindung am hepatischen Endothel nach partieller Hepatektomie beobachtet. Die deutliche Ablagerung des Fibrinogens in der Lebermikrozirkulation bewies eine Aktivierung und Beanspruchung des Koagulationssystems unter einem stark gesteigerten Scherstress unmittelbar nach der Leberresektion. In dieser Studie wurde der Pathomechanismus des Leberversagens nach Hepatektomie mit Hilfe der in-vivo-Mikroskopie und verschiedener Mausmodelle innovativ untersucht. Dies war auch die erste Beschreibung einer intravitalen Zwei-Photonen-Mikroskopie-Studie im Zusammenhang mit dem hepatektomie-induzierten Leberversagen. Die klinische Relevanz der vorgestellten Komponenten der Koagulationskaskade für therapeutische Interventionen bleibt in weiterführenden Studien zu überprüfen.Post-hepatectomy liver failure or Small-for-size syndrome is a potentially fatal complication after extended liver resection or partial liver transplantation. This is caused by supraphysiologic perfusion in the remnant liver and microcirculatory injury. However, the exact pathophysiological mechanism of microvascular injury in the acute phase is still unclear. In the present work, the impact of important components from the coagulation cascade was investigated in acute liver injury after partial hepatectomy. First, a mouse model suitable for intravital microscopic examination was established. After extended hepatectomy, an increased endothelial-leukocyte interaction was observed in addition to perfusion failure. Serine proteases affected both microperfusion and liver injury by inducing early leukocyte recruitment after partial hepatectomy. A platelet depletion model was used to investigate the influence of platelets after extended hepatectomy. The results indicated that platelets regulated the recruitment of different leukocyte subpopulations through an ICAM-1-dependent pattern. In addition, the platelet depletion resulted in significantly improved liver function. Furtherly, the role of PAR-4, an activator of platelets, was investigated using two-photon microscopy. Platelet activation via PAR-4 induced microthrombosis and increased neutrophil- platelet interactions in hepatic sinusoids, exacerbating acute liver injury after partial hepatectomy. Finally, fibrinogen deposition to hepatic endothelium after partial hepatectomy was investigated. The deposition of fibrinogen in the liver microcirculation reflected the activation of the coagulation system under increased shear stress immediately after liver resection. In this study, the pathomechanism of post-hepatectomy liver failure was innovatively investigated by utilizing in vivo microscopy and different murine models. This was also the first description of in vivo two-photon microscopy study in the context of post-hepatectomy liver failure. The clinical relevance of the presented components of the coagulation cascade as therapeutic interventions remains to be verified in further studies

Convergence and value in environmental and animal ethics

This thesis concerns the plausibility of arguments that certain normative ethical theories converge on the answer to the practical question of normative ethics (e.g., What (morally) ought I to do?) and the explanatory question of normative ethics (e.g., What explains why certain actions are permissible, required, or forbidden?). I explore different strategies for arguing that normative ethical theories converge on the answer to these questions. I then turn to the prospects of convergence between certain normative ethical theories in environmental ethics and animal ethics. In environmental ethics, I consider the prospects of convergence between Anthropocentrism (i.e., human-centred ethics) and Non-Anthropocentrism. I argue that Bryan Norton’s influential convergence argument fails to show that there is convergence between these two views. I then propose my own version of Anthropocentrism (i.e., “Broad Anthropocentrism”) and argue that it exhibits some degree of convergence with NonAnthropocentrism on the answer to both the practical and the explanatory question of normative ethics. In animal ethics, I consider the prospects of convergence between Utilitarianism and a moral rights-based approach. I argue that a prominent attempt to argue for convergence between these theories fails because it relies on implausible or incomplete versions of a moral rights theory. Finally, I shift focus from convergence on the answer to the practical and explanatory questions to convergence on the question of whether one ought to care about nature and animals. I argue that there is a large amount of convergence between Broad Anthropocentrism and Non-Anthropocentrism on the answer to the questions of “Should one finally care about nature?” and “Why should one finally care about nature?” I also argue that there is a fair amount of convergence between Utilitarianism and a plausible moral rights view on the answer to the questions, “Should I care about animals?” and “Why should I care about animals?

Diammonium bis­[(2-amino­acetato-κ2 N,O)(2,2′-bipyridine-κ2 N,N′)(N,N-dimethyl­formamide-κO)copper(II)] hexa­cosa­oxidoocta­molybdate(VI)

The title compound, (NH4)2[Cu(C2H4NO2)(C10H8N2)(C3H7NO)]2[Mo8O26], contains a centrosymmetric β-type octa­molybdate anion, two copper(II) complex cations and two ammonium ions. The CuII atom is coordinated in a square-pyramidal geometry by a 2,2′-bipyridine and a 2-amino­acetate ligands in the basal plane and by an O atom of N,N-dimethyl­formamide in the apical position. The anions and cations are linked by N—H⋯O hydrogen bonds into a three-dimensional network

Learning Rich Features for Gait Recognition by Integrating Skeletons and Silhouettes

Gait recognition captures gait patterns from the walking sequence of an individual for identification. Most existing gait recognition methods learn features from silhouettes or skeletons for the robustness to clothing, carrying, and other exterior factors. The combination of the two data modalities, however, is not fully exploited. Previous multimodal gait recognition methods mainly employ the skeleton to assist the local feature extraction where the intrinsic discrimination of the skeleton data is ignored. This paper proposes a simple yet effective Bimodal Fusion (BiFusion) network which mines discriminative gait patterns in skeletons and integrates with silhouette representations to learn rich features for identification. Particularly, the inherent hierarchical semantics of body joints in a skeleton is leveraged to design a novel Multi-Scale Gait Graph (MSGG) network for the feature extraction of skeletons. Extensive experiments on CASIA-B and OUMVLP demonstrate both the superiority of the proposed MSGG network in modeling skeletons and the effectiveness of the bimodal fusion for gait recognition. Under the most challenging condition of walking in different clothes on CASIA-B, our method achieves the rank-1 accuracy of 92.1%.Comment: The paper is under consideration at Multimedia Tools and Application