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Since the description of sepsis by Schottmüller in 1914, the amount on knowledge available on sepsis and its underlying pathophysiology has substantially increased. Epidemiologic examinations of abdominal septic shock patients show the potential for high risk posed by and the extensive therapy situation in the intensive care unit (ICU) (5). Unfortunately, until now it has not been possible to significantly reduce the mortality rate of septic shock, which is as high as 50-60% worldwide, although PROWESS' results (1) are encouraging. This paper summarizes the main results of the MEDAN project and their medical impacts. Several aspects are already published, see the references. The heterogeneity of patient groups and the variations in therapy strategies is seen as one of the main problems for sepsis trials. In the MEDAN multi-center study of 71 intensive care units in Germany, a group of 382 patients made up exclusively of abdominal septic shock patients who met the consensus criteria for septic shock (3) was analysed. For use within scores or stand-alone experiments variables are often studied as isolated variables, not as a multidimensional whole, e.g. a recent study takes a look at the role thrombocytes play (15). To avoid this limitation, our study compares several established scores (SOFA, APACHE II, SAPS II, MODS) by a multi-dimensional neuronal network analysis. For outcome prediction the data of 382 patients was analysed by using most of the commonly documented vital parameters and doses of medicine (metric variables). Data was collected in German hospitals from 1998 to 2001. The 382 handwritten patient records were transferred to an electronic database giving the amount of 2.5 million data entries. The metric data contained in the database is composed of daily measurements and doses of medicine. We used range and plausibility checks to allow no faulty data in the electronic database. 187 of the 382 patients are deceased (49 %).
Data driven automatic model selection and parameter adaptation – a case study for septic shock
(2004)
In bioinformatics, biochemical pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically learning the parameters is necessary. This paper propose as model selection criterion the least complex description of the observed data by the model, the minimum description length. For the small, but important example of inflammation modeling the performance of the approach is evaluated.
In bioinformatics, biochemical signal pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically obtaining the most appropriate model and learning its parameters is extremely interesting. One of the most often used approaches for model selection is to choose the least complex model which “fits the needs”. For noisy measurements, the model which has the smallest mean squared error of the observed data results in a model which fits too accurately to the data – it is overfitting. Such a model will perform good on the training data, but worse on unknown data. This paper propose as model selection criterion the least complex description of the observed data by the model, the minimum description length. For the small, but important example of inflammation modeling the performance of the approach is evaluated. Keywords: biochemical pathways, differential equations, septic shock, parameter estimation, overfitting, minimum description length.
In bioinformatics, biochemical pathways can be modeled by many differential equations. It is still an open problem how to fit the huge amount of parameters of the equations to the available data. Here, the approach of systematically learning the parameters is necessary. In this paper, for the small, important example of inflammation modeling a network is constructed and different learning algorithms are proposed. It turned out that due to the nonlinear dynamics evolutionary approaches are necessary to fit the parameters for sparse, given data. Keywords: model parameter adaption, septic shock. coupled differential equations, genetic algorithm.
It is shown that between one-turn pushdown automata (1-turn PDAs) and deterministic finite automata (DFAs) there will be savings concerning the size of description not bounded by any recursive function, so-called non-recursive tradeoffs. Considering the number of turns of the stack height as a consumable resource of PDAs, we can show the existence of non-recursive trade-offs between PDAs performing k+ 1 turns and k turns for k >= 1. Furthermore, non-recursive trade-offs are shown between arbitrary PDAs and PDAs which perform only a finite number of turns. Finally, several decidability questions are shown to be undecidable and not semidecidable.
RDF is widely used in order to catalogue the chaos of data across the internet. But these descriptions must be stored, evaluated, analyzed and verified. This creates the need to search for an environment to realize these aspects and strengthen RDFs influence. InterSystems postrelational database Caché exposes many features that are similar to RDF and provide persistence with semantic part. Some models for relational databases exist but these lack features like object-oriented data-structures and multidimensional variables. The aim of this thesis is to develop an RDF model for Caché that saves RDF data in an object-oriented form. Furthermore an interface for importing RDF data will be presented and implemented.
Configuration, simulation and visualization of simple biochemical reaction-diffusion systems in 3D
(2004)
Background In biological systems, molecules of different species diffuse within the reaction compartments and interact with each other, ultimately giving rise to such complex structures like living cells. In order to investigate the formation of subcellular structures and patterns (e.g. signal transduction) or spatial effects in metabolic processes, it would be helpful to use simulations of such reaction-diffusion systems. Pattern formation has been extensively studied in two dimensions. However, the extension to three-dimensional reaction-diffusion systems poses some challenges to the visualization of the processes being simulated. Scope of the Thesis The aim of this thesis is the specification and development of algorithms and methods for the three-dimensional configuration, simulation and visualization of biochemical reaction-diffusion systems consisting of a small number of molecules and reactions. After an initial review of existing literature about 2D/3D reaction-diffusion systems, a 3D simulation algorithm (PDE solver), based on an existing 2D-simulation algorithm for reaction-diffusion systems written by Prof. Herbert Sauro, has to be developed. In a succeeding step, this algorithm has to be optimized for high performance. A prototypic 3D configuration tool for the initial state of the system has to be developed. This basic tool should enable the user to define and store the location of molecules, membranes and channels within the reaction space of user-defined size. A suitable data structure has to be defined for the representation of the reaction space. The main focus of this thesis is the specification and prototypic implementation of a suitable reaction space visualization component for the display of the simulation results. In particular, the possibility of 3D visualization during course of the simulation has to be investigated. During the development phase, the quality and usability of the visualizations has to be evaluated in user tests. The simulation, configuration and visualization prototypes should be compliant with the Systems Biology Workbench to ensure compatibility with software from other authors. The thesis is carried out in close cooperation with Prof. Herbert Sauro at the Keck Graduate Institute, Claremont, CA, USA. Due to this international cooperation the thesis will be written in English.
In the last decade, much effort went into the design of robust third-person pronominal anaphor resolution algorithms. Typical approaches are reported to achieve an accuracy of 60-85%. Recent research addresses the question of how to deal with the remaining difficult-toresolve anaphors. Lappin (2004) proposes a sequenced model of anaphor resolution according to which a cascade of processing modules employing knowledge and inferencing techniques of increasing complexity should be applied. The individual modules should only deal with and, hence, recognize the subset of anaphors for which they are competent. It will be shown that the problem of focusing on the competence cases is equivalent to the problem of giving precision precedence over recall. Three systems for high precision robust knowledge-poor anaphor resolution will be designed and compared: a ruleset-based approach, a salience threshold approach, and a machine-learning-based approach. According to corpus-based evaluation, there is no unique best approach. Which approach scores highest depends upon type of pronominal anaphor as well as upon text genre.
Assessing enhanced knowledge discovery systems (eKDSs) constitutes an intricate issue that is understood merely to a certain extent by now. Based upon an analysis of why it is difficult to formally evaluate eKDSs, it is argued for a change of perspective: eKDSs should be understood as intelligent tools for qualitative analysis that support, rather than substitute, the user in the exploration of the data; a qualitative gap will be identified as the main reason why the evaluation of enhanced knowledge discovery systems is difficult. In order to deal with this problem, the construction of a best practice model for eKDSs is advocated. Based on a brief recapitulation of similar work on spoken language dialogue systems, first steps towards achieving this goal are performed, and directions of future research are outlined.
We modify the concept of LLL-reduction of lattice bases in the sense of Lenstra, Lenstra, Lovasz [LLL82] towards a faster reduction algorithm. We organize LLL-reduction in segments of the basis. Our SLLL-bases approximate the successive minima of the lattice in nearly the same way as LLL-bases. For integer lattices of dimension n given by a basis of length 2exp(O(n)), SLLL-reduction runs in O(n.exp(5+epsilon)) bit operations for every epsilon > 0, compared to O(exp(n7+epsilon)) for the original LLL and to O(exp(n6+epsilon)) for the LLL-algorithms of Schnorr (1988) and Storjohann (1996). We present an even faster algorithm for SLLL-reduction via iterated subsegments running in O(n*exp(3)*log n) arithmetic steps.