Visual fields measured with standard automated perimetry are a benchmark test for determining retinal function in ocular pathologies such as glaucoma. Their monitoring over time is crucial in detecting change in disease course and, therefore, in prompting clinical intervention and defining endpoints in clinical trials of new therapies. However, conventional change detection methods do not take into account non-stationary measurement variability or spatial correlation present in these measures. An inferential statistical model, denoted ‘Analysis with Non-Stationary Weibull Error Regression and Spatial enhancement’ (ANSWERS), was proposed. In contrast to commonly used ordinary linear regression models, which assume normally distributed errors, ANSWERS incorporates non-stationary variability modelled as a mixture of Weibull distributions. Spatial correlation of measurements was also included into the model using a Bayesian framework. It was evaluated using a large dataset of visual field measurements acquired from electronic health records, and was compared with other widely used methods for detecting deterioration in retinal function. ANSWERS was able to detect deterioration significantly earlier than conventional methods, at matched false positive rates. Statistical sensitivity in detecting deterioration was also significantly better, especially in short time series. Furthermore, the spatial correlation utilised in ANSWERS was shown to improve the ability to detect deterioration, compared to equivalent models without spatial correlation, especially in short follow-up series. ANSWERS is a new efficient method for detecting changes in retinal function. It allows for better detection of change, more efficient endpoints and can potentially shorten the time in clinical trials for new therapies.
Kinematic analysis of swimming is of interest to improve swimming performances. Although the video recordings of underwater swimmers are commonly used, the available methodologies are rarely precise enough to adequately estimate the three dimensional (3D) joint kinematics. This is mainly due to difficulties in obtaining the required kinematic parameters (anatomical landmarks, joint centres and reference frames) in the swimming environment. In this paper we propose a procedure to investigate the right upper limb's 3D kinematics during front crawl swimming in terms of all elbow and shoulder degrees of freedom (three rotations of the shoulder, two of the elbow). The method is based upon the calibrated anatomical systems technique (CAST), a technique widely used in clinics, which allows estimation of anatomical landmarks of interest even when they are not directly visible. An automatic tracking technique was adopted. The intra-operator repeatability of the manual tracking was also assessed. The root mean squared difference of three anatomical landmarks, processed five times, is always lower than 8 mm. The mean of the root mean squared difference between trajectories obtained with the different methodologies was found to be lower than 20 mm. Results showed that complete 3D kinematics of at least twice as many frames than without CAST can be reconstructed faster and more precisely.
Bayesian networks (BNs) are probabilistic models used for classification and clustering in several fields. Their ability to deal with unobserved variables and to integrate data and expert knowledge make them an appropriate technique for modeling eye functionality measurements in glaucoma. In this study, a set of BNs is used to simultaneously perform classification of early glaucoma and cluster data into different stages of disease. A novel learning algorithm that combines clustering and quasi-greedy search is also proposed. The classification performances of the models are evaluated on an independent dataset, while the clusters are compared to K-means, previous publications, and direct knowledge. The use of clustering and structure learning enabled the exploration of the visual field patterns of the disease while obtaining good results both on pre- (50% sensitivity at 90% specificity) and post- (85% sensitivity at 90% specificity) diagnosis data. Clusters obtained were insightful and in conformity with consolidated knowledge in the field.
Treatment of Ca2+-loaded mitochondria with both aluminum and tyramine results in a swelling of higher amplitude than with aluminum alone, while tyramine alone is ineffective. The phenomenon is accompanied by H2O2 production and thiol and pyridine nucleotide oxidation. Cyclosporin A, N-ethylmaleimide or dithioerythritol completely prevent these effects, while catalase exhibits a lower inhibition, pointing to the induction of the permeability transition (MPT) by an oxidative stress. Reactive oxygen species are generated by the interaction of aluminum with the inner membrane and the oxidation of tyramine by monoamine oxidase on the outer membrane. This different localization determines the oxidation of critical thiol groups located on both internal and external sides of pore-forming structures, resulting in MPT induction. The reduced effect by aluminum or the inefficacy by tyramine, when implied alone, can be attributable to the oxidation of thiol groups located only on the internal or external side, respectively. Ultrastructural observations show that aluminum plus tyramine induce the typical configuration of mitochondria that have undergone the MPT. Instead, with aluminum alone, the sensitive subpopulation, although swollen, preserves the outer membrane and shows an apparently orthodox configuration.
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