Evolution of moments and correlations in non-renewal escape-time processes

The theoretical description of non-renewal stochastic systems is a challenge. Analytical results are often not available or can only be obtained under strong conditions, limiting their applicability. Also, numerical results have mostly been obtained by ad-hoc Monte--Carlo simulations, which are usually computationally expensive when a high degree of accuracy is needed. To gain quantitative insight into these systems under general conditions, we here introduce a numerical iterated first-passage time approach based on solving the time-dependent Fokker--Planck equation (FPE) to describe the statistics of non-renewal stochastic systems. We illustrate the approach using spike-triggered neuronal adaptation in the leaky and perfect integrate-and-fire model, respectively. The transition to stationarity of first-passage time moments and their sequential correlations occur on a non-trivial timescale that depends on all system parameters. Surprisingly this is so for both single exponential and scale-free power-law adaptation. The method works beyond the small noise and timescale separation approximations. It shows excellent agreement with direct Monte Carlo simulations, which allows for the computation of transient and stationary distributions. We compare different methods to compute the evolution of the moments and serial correlation coefficients (SCC), and discuss the challenge of reliably computing the SCC which we find to be very sensitive to numerical inaccuracies for both the leaky and perfect integrate-and-fire models. In conclusion, our methods provide a general picture of non-renewal dynamics in a wide range of stochastic systems exhibiting short and long-range correlations

First passage times in integrate-and-fire neurons with stochastic thresholds

We consider a leaky integrate--and--fire neuron with deterministic subthreshold dynamics and a firing threshold that evolves as an Ornstein-Uhlenbeck process. The formulation of this minimal model is motivated by the experimentally observed widespread variation of neural firing thresholds. We show numerically that the mean first passage time can depend non-monotonically on the noise amplitude. For sufficiently large values of the correlation time of the stochastic threshold the mean first passage time is maximal for non-vanishing noise. We provide an explanation for this effect by analytically transforming the original model into a first passage time problem for Brownian motion. This transformation also allows for a perturbative calculation of the first passage time histograms. In turn this provides quantitative insights into the mechanisms that lead to the non-monotonic behaviour of the mean first passage time. The perturbation expansion is in excellent agreement with direct numerical simulations. The approach developed here can be applied to any deterministic subthreshold dynamics and any Gauss-Markov processes for the firing threshold. This opens up the possibility to incorporate biophysically detailed components into the subthreshold dynamics, rendering our approach a powerful framework that sits between traditional integrate-and-fire models and complex mechanistic descriptions of neural dynamics

Prognostic significance of DNA cytometry in cutaneous malignant lymphomas.

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML

Cirulating Sézary Cells in the Diagnosis of Sézary Syndrome (Quantitative and Morphometric Analyses)

Plastic-embedded circulating Sézary cells were examined in semithin and thin sections (assisted by the nuclear contour index-NCI). Eight cases of Sézary syndrome were analyzed as well as 11 controls (3 cases of widespread eczemas and 8 cases of erythroderma), 7 cases of mycosis fungoides, and 3 healthy individuals. Discriminating criteria between Sézary syndrome and benign diseases were sought: in addition to Sézary cells (NCI > 6.5) intermediate lymphocytes (5.0 < NCI ≤ 6.5) proved to be helpful. Cases with Sézary syndrome were clearly differentiated when the following 3 ultrastructural criteria were fulfilled: (1) Sézary cells (SC) > 9%; (2) intermediate lymphocytes (IL) > 20%; (3) the sum of SC and IL > 37%.A good correlation between thin and semithin sections was obtained (correlation coefficient for Sézary cells r = 0.82). Usually the values of SC were slightly higher on thin sections. The diagnosis of SS can be made on semithin sections when the ultrastructural criteria are fulfilled. In this way 8 of 12 samples of Sézary syndrome were correctly classified. Therefore, semithin sections (studied by light microscopy) are recommended as a routine method in the diagnosis of cases suspected of Sézary syndrome, whereas thin sections (studied by electron microscopy) appeared to be necessary in problem cases only

Feasibility and Usage of RFID in Small and Medium-sized Companies in Germany and the Netherlands

This article describes results of an analysis of RFID projects carried out in cooperation of small and medium sized Enterprises (SME), Fontys Hogescholen, Venlo, Netherlands and Niederrhein University of Applied Sciences, Moenchengladbach, Germany. Main content and questions are: Who can be a driver and main beneficiaries of the potential of RFID for SME? What are the main objectives to use RFID? Which RFID applications are suitable? Which RFID technologies are used in SME

Design of a tourist driven bandwidth determined MultiModal mobile presentation system

In this paper we report on first experiences with a new software architecture for agent toolkits. Agent toolkits mainly consist of a software system that defines an agency, which is responsible to host software agents. Most architectures developed so far already define a large set of services, for example for agent migration, communication, and tracking. We propose to employ a kernel-based approach, where the kernel only provides fundamental concepts and functions common in all toolkits and abstracts from any of these services. We were able to show that in particular agent migration can be implemented as an optional service. We believe that this architecture is a useful foundation for research on agent-related topics as it allows research groups to implement their own results as a service which can be used by other groups running an agent system based on the same architecture

Predicting Survival for Veno-Arterial ECMO Using Conditional Inference Trees-A Multicenter Study

BACKGROUND Despite increasing use and understanding of the process, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy is still associated with considerable mortality. Personalized and quick survival predictions using machine learning methods can assist in clinical decision making before ECMO insertion. METHODS This is a multicenter study to develop and validate an easy-to-use prognostic model to predict in-hospital mortality of VA-ECMO therapy, using unbiased recursive partitioning with conditional inference trees. We compared two sets with different numbers of variables (small and comprehensive), all of which were available just before ECMO initiation. The area under the curve (AUC), the cross-validated Brier score, and the error rate were applied to assess model performance. Data were collected retrospectively between 2007 and 2019. RESULTS 837 patients were eligible for this study; 679 patients in the derivation cohort (median (IQR) age 60 (49 to 69) years; 187 (28%) female patients) and a total of 158 patients in two external validation cohorts (median (IQR) age 57 (49 to 65) and 70 (63 to 76) years). For the small data set, the model showed a cross-validated error rate of 35.79% and an AUC of 0.70 (95% confidence interval from 0.66 to 0.74). In the comprehensive data set, the error rate was the same with a value of 35.35%, with an AUC of 0.71 (95% confidence interval from 0.67 to 0.75). The mean Brier scores of the two models were 0.210 (small data set) and 0.211 (comprehensive data set). External validation showed an error rate of 43% and AUC of 0.60 (95% confidence interval from 0.52 to 0.69) using the small tree and an error rate of 35% with an AUC of 0.63 (95% confidence interval from 0.54 to 0.72) using the comprehensive tree. There were large differences between the two validation sets. CONCLUSIONS Conditional inference trees are able to augment prognostic clinical decision making for patients undergoing ECMO treatment. They may provide a degree of accuracy in mortality prediction and prognostic stratification using readily available variables

The T-pod is as stable as supraacetabular fixation using 1 or 2 Schanz screws in partially unstable pelvic fractures: a biomechanical study

Introduction: Unstable fractures of the pelvis remain the predominant cause of severe hemorrhage, shock and early death in severely injured patients. The use of pelvic binders has become increasingly popular, particularly in the preclinical setting. There is currently insufficient evidence available about the stability of the pelvic binder versus supraacetabular fixation using 1 or 2 Schanz screws. We aimed to analyze the stability of the pelvic binder and supraacetabular fixateurs using either 1 or 2 Schanz screws in a cadaver model of an induced pelvic B-type fracture. Materials and methods: The study was undertaken in 7 human fresh-frozen cadaveric pelvises with induced AO-type B fractures. Three stabilization techniques were compared: T-POD (pelvic bandage), supraacetabular external fixator with 1 pin on each side and external fixator with 2 pins on each side. Stability and stiffness were analyzed in a biomechanical testing machine using a 5-step protocol with static and dynamic loading, dislocation data were retrieved by ultrasound sensors at the fracture sites. Results: No significant differences in fracture fragment displacement were detected when using either the T-POD, a 1-pin external fixator or a 2-pin external fixator (P > 0.05). The average difference in displacement between the three methods was < 1 mm. Conclusions: Pelvic binders are suitable for reduction of pelvic B-type fractures. They provide stability comparable to that of supraacetabular fixators, independently of whether 1 or 2 Schanz screws per side are used. Pelvic binders provide sufficient biomechanical stability for transferring patients without the need to first replace them with surgically applied external fixators. However, soft tissue irritation has to be taken into consideration and prolonged wear should be avoided. Level of evidence: Level III