Connections of the vestibular nuclei in the rabbit

This thesis descnbes the afferent, efferent and intrinsic connections of the vestibular nuclei in the Dutch belted rabbit. Different anatomical tracing techniques were used to study these projections. A description of the vestibular complex was added, since recent data for the rabbit are scarce (Chapter 2). A comparison between cytoarchitecture and staining for acetylcholinesterase and cytochromoxidase supported the subdivision of the central magnocellular area of the vestibular complex into a dorsal region comprising the lateral vestibular nucleus of Deiters and the ventrally located magnocellular portion of the medial vestibular nucleus. Additional evidence supporting this distinction came from a detailed analysis of the primary vestibular input in the rabbit (Chapter 3). The central projections of the vestibular nerve were investigated with anterograde axonal transport of wheatgerm agglutinin conjugated horseradish peroxidase (WGA-HRP) and tritiated leucine following injection in the vestibular ganglion. Labeled fibers and terminal ramifications were observed throughout the vestibular complex, including the magnocellular part of the medial vestibular nucleus, but they were absent from lateral vestibular nucleus. The absence of a projection of the vesnbular nerve to lateral vestibular nucleus is in accordance with the findings in other mammals (Voogd, 1964, Korte, 1979, Carleton and Carpenter, 1984). Termination in the cortex was restricted to the vermis. Small numbers of mossy fiber terminals were present bilaterally, close to the midline in lobules I and II, and in the depth of the main fissures separating the lobules II- VI. In the posterior vermis labeled mossy fiber terminals were found in lobule X and the ventral aspect of lobule IXd. Here the entire ipsilateral hemivermis contained many terminals, while contralaterally fewer mossy fiber tenninals were present in the medial one-third of these lobules. Labeled mossy fibers and terminals were absent from the flocculus and adjacent ventral paraflocculus

Secondary vestibulocerebellar projections to the flocculus and uvulo-nodular lobule of the rabbit: a study using HRP and double fluorescent tracer techniques

The distribution of vestibular neurons projecting to the flocculus and the nodulus and uvula of the caudal vermis (Larsell's lobules X and IX) was investigated with retrograde axonal transport of horseradish peroxidase and the fluorescent tracers Fast Blue, Nuclear Yellow and Diamidino Yellow. The presence of collateral axons innervating the flocculus on one hand and the nodulus and uvula on the other was studied with simultaneous injection of the different fluorescent tracers. The distribution of vestibular neurons projecting to either flocculus or caudal vermis is rather similar and has a bilateral symmetry. The projection from the magnocellular medial vestibular nucleus is very sparse, while that from the lateral vestibular nucleus is absent. The majority of labeled neurons was found in the medial, superior, and descending vestibular nuclei, in that order. Double labeled neurons were distributed in a similar way as the single labeled ones. Labeled neurons project to the nodulus and uvula, the flocculus, and to both parts of the cerebellum simultaneously in a ratio of 12:4:1. Five different populations of vestibulocerebellar neurons can be distinguished on the basis of their projection to the: (1) ipsilateral flocculus, (2) contralateral flocculus, (3) ipsilateral flocculus and nodulus/uvula, (4) contralateral flocculus and nodulus/uvula, and (5) nodulus/uvula

Identifying and characterizing high-risk clusters in a heterogeneous ICU population with deep embedded clustering

Critically ill patients constitute a highly heterogeneous population, with seemingly distinct patients having similar outcomes, and patients with the same admission diagnosis having opposite clinical trajectories. We aimed to develop a machine learning methodology that identifies and provides better characterization of patient clusters at high risk of mortality and kidney injury. We analysed prospectively collected data including co-morbidities, clinical examination, and laboratory parameters from a minimally-selected population of 743 patients admitted to the ICU of a Dutch hospital between 2015 and 2017. We compared four clustering methodologies and trained a classifier to predict and validate cluster membership. The contribution of different variables to the predicted cluster membership was assessed using SHapley Additive exPlanations values. We found that deep embedded clustering yielded better results compared to the traditional clustering algorithms. The best cluster configuration was achieved for 6 clusters. All clusters were clinically recognizable, and differed in in-ICU, 30-day, and 90-day mortality, as well as incidence of acute kidney injury. We identified two high mortality risk clusters with at least 60%, 40%, and 30% increased. ICU, 30-day and 90-day mortality, and a low risk cluster with 25–56% lower mortality risk. This machine learning methodology combining deep embedded clustering and variable importance analysis, which we made publicly available, is a possible solution to challenges previously encountered by clustering analyses in heterogeneous patient populations and may help improve the characterization of risk groups in critical care