Ray Paton

Early identification of sepsis and mortality risks through simple, rapid clot-waveform analysis. Implications of lipoprotein-complexed C reactive protein formation.

Abstract Objective. To determine if the rapid waveform profile of the activated partial thromboplastin time (aPTT) assay, which detects lipoprotein-complexed C reactive protein (LCCRP) formation, predicts sepsis and mortality in critically ill patients. Design. Observational, cohort study. Setting. General intensive therapy unit (ITU) of a tertiary care hospital. Patients and participants. A total of 1187 consecutive patients admitted to the ITU. Intervention. Activated partial thromboplastin time transmittance waveform analysis was performed within the first hour of admission to the ITU. The degree of change causing a biphasic waveform was quantified through the drop in light transmittance level. Measurements and results. Three hundred forty-six patients had a biphasic waveform on admission to the ITU with a mortality rate of 44% compared with 26% for those with normal waveforms. Logistic regression models showed direct correlation between the likelihood for sepsis and in-patient mortality with increasing waveform abnormalities. The mortality fraction was 0.3 with normal waveforms versus 0.6 when the light transmittance decreased by 30%. The odds ratio (OR) for mortality and sepsis were 4.5 and 11, respectively, from the most abnormal to normal aPTT waveforms. These were comparable with APACHE II scores and superior to those estimated by CRP for mortality (OR 2.3) / sepsis (OR 6.4) prediction. Conclusion. Waveform analysis within the first hour of ITU admission is a single, simple and rapid method of identifying the risks of mortality and sepsis. Its measure of LCCRP formation shows superior prediction over CRP alone and it warrants further assessment as a tool to triage and target prompt, appropriate treatment in the ITU.

Computation in cellular and molecular biological systems

A selection of papers presented at the First International Workshop on Information Processing in Cells and Tissues (IPCAT 95). The book contains contributions from mathematicians, biochemists, cell biologists, physiologists, and computer scientists. It is multidisciplinary in nature and deals with integrative aspects of information processing, cellular systems and dynamical methods.

Evolvable social agents for bacterial systems modeling

We present two approaches to the individual-based modeling (IbM) of bacterial ecologies and evolution using computational tools. The IbM approach is introduced, and its important complementary role to biosystems modeling is discussed. A fine-grained model of bacterial evolution is then presented that is based on networks of interactivity between computational objects representing genes and proteins. This is followed by a coarser grained agent-based model, which is designed to explore the evolvability of adaptive behavioral strategies in artificial bacteria represented by learning classifier systems. The structure and implementation of the two proposed individual-based bacterial models are discussed, and some results from simulation experiments are presented, illustrating their adaptive properties.

Some Computational Models at the Cellular Level

A number of viewpoints on how a cell can be modelled are discussed in this paper in light of the ability it has to process information. The paper begins with a very brief summary of four general types of computation: sequential, parallel, distributed, and emergent. These form the general framework from which a number of comparisons are made. Several metaphors are introduced to enable reflections to be made about cellular computational properties. The most important metaphor, namely the cell as a machine, is discussed, and then a number of other ideas are introduced that complement much current thinking in this area. The idea of networks or circuits in the cell is then developed, as this provides a means of describing the mechanisms within a machine. Following on from this, three further metaphors are applied in order to overcome certain limitations in current machine thinking, cell-as-society, cell-as-text, and cell-as-field.

Glue, Verb and Text Metaphors in Biology

Metaphor influences the construction of biological models and theories and the analysis of its use can reveal important tools of thought. Some aspects of biological organisation are investigated through the analysis of metaphors associated with treating biosystems as a kind of text. In particular, the use of glue and verbs is considered. Some of the reasons why glue is important in the construction of hierarchies are pursued in the light of specific examples, and some of the conceptual links between glue in biology and other domains is discussed. Verbs are shown to be important in the construction of networks. Some of the relations between glue, verb and text are considered and the text metaphor is placed within a much broader context of ideas associated with form, relation and system. The paper concludes with comments on the nature of biological information and the need for extending or better understanding the verbal vocabulary.

Process, structure and context in relation to integrative biology

This paper seeks to provide some integrative tools of thought regarding biological function related to ideas of process, structure, and context. The incorporation of linguistic and mathematical thinking is discussed within the context of managing thinking about natural systems as described by Robert Rosen. Examples from ecology, protein networks, and liver function are introduced to illustrate key ideas. It is hoped that these tools of thought, and the further work needed to mobilise such ideas, will continue to address a number of issues raised and pursued by Michael Conrad, such as the seed-germination model and vertical information processing.

Toward principles for the representation of hierarchical knowledge in formal ontologies

Abstract Early ontological engineering methodologies have necessarily focussed on the management of the whole ontology development process. There is a corresponding need to provide advice to the ontological engineer on the finer details of ontology construction. Here, we specifically address the representation of hierarchical relationships in an ontology. We identify five types of problem that may be encountered in moving from an informal description of a domain to a formal representation of hierarchical knowledge. Each problem type is discussed from the perspective of knowledge sharing and examples from biological ontologies are used to illustrate each type.

Two aspects of the validation and verification of knowledge-based systems

Two research projects that have examined problems related to system verification and validation and the associated issue of maintenance are described. The Mekas (Methodology for Knowledge Analysis) Project has developed a method to give knowledge engineers a thorough characterization of the domain, that is, a full description of the ontology, structure, functions, and theories that underpin the domain. This provides a coherent framework within which a knowledge base can be more readily identified with key aspects of the domain, aiding verification and validation. The second project, known as MAKE (Maintenance Assistance for Knowledge Engineers), was aimed at the process of constructing and revising the knowledge base. It is argued that the primary focus of verification and validation must be on the models, and the transitions between them, rather than simply on the executable representation.<<ETX>>

Transfer of Natural Metaphors to Parallel Problem Solvin Applications

Metaphors are crucial to research as they provide alternative perspectives of seeing and understanding the world; indeed, they have been the basis of many scientific and technological creations. In this paper, we argue that progress in parallel problem solving research could be invaluably enhanced if metaphors that exhibit parallelism, in terms of their underlying structure and the ways they work, are studied. Using biological examples, we demonstrate how nature furnishes us with numerous metaphors. An attempt is made to show how an understanding of the way such metaphors work can help us manage our conceptualisation of complex problems as well as reveal new directions towards parallel problem applications.

JavaSpaces – An Affordable Technology for the Simple Implementation of Reusable Parallel Evolutionary Algorithms

Evolutionary algorithms are powerful optimisation methods and have been applied successfully in many scientific areas including life sciences. However, they have high computational demands. In order to alleviate this, parallel evolutionary algorithms have been developed. Unfortunately, the implementation of parallel evolutionary algorithms can be complicated, and often requires specific hardware and software environments. This frequently results in very problem-specific parallel evolutionary algorithms with little scope for reuse. This paper investigates the use of the JavaSpaces technology to overcome these problems. This technology is free of charge, simplifies the implementation of parallel/distributed applications, and is independent of hardware and software environments. Several approaches for the implementation of different parallel evolutionary algorithms using JavaSpaces are proposed and successfully tested.