The component-based architecture of the HELIOS medical software engineering environment.

The constitution of highly integrated health information networks and the growth of multimedia technologies raise new challenges for the development of medical applications. We describe in this paper the general architecture of the HELIOS medical software engineering environment devoted to the development and maintenance of multimedia distributed medical applications. HELIOS is made of a set of software components, federated by a communication channel called the HELIOS Unification Bus. The HELIOS kernel includes three main components, the Analysis-Design and Environment, the Object Information System and the Interface Manager. HELIOS services consist in a collection of toolkits providing the necessary facilities to medical application developers. They include Image Related services, a Natural Language Processor, a Decision Support System and Connection services. The project gives special attention to both object-oriented approaches and software re-usability that are considered crucial steps towards the development of more reliable, coherent and integrated applications.

Documentation and information services in the HELIOS project.

In a modern software project large amounts of documentation is produced. All parts of the complex software system require extensive documentation--both for reference purposes and promotional reasons. However, there are some aspects that often are forgotten or badly implemented; (i) the availability of on-line documentation, (ii) integration of the different formats of documentation, and (iii) the world wide promotional aspect. To solve these problems, the Helios project has chosen to integrate its public documentation and software material into a hypertext system using the World Wide Web.

Usability and efficiency. The HELIOS approach to development of user interfaces.

This paper describes the user interface related services of the HELIOS project. The design and implementation of efficient user interfaces is a prerequisite for successful introduction of computer support in health care ward units. Design principles must be based on a basic understanding of cognitive aspects of human-computer interaction, as well as on detailed knowledge about the specific needs and requirements of the health care professionals. In the HELIOS project, a style guide for design of user interfaces has been developed. The style guide defines detailed design guide-lines together with a set of interface elements specified for the ward domain. Development tools for construction and implementation of user interfaces to ward applications have been developed and integrated into the HELIOS SEE. The tools are based on the TeleUSE product, which has been extended and adjusted to the HELIOS specifications. A set of new widgets, designed to implement health care interface elements, has been incorporated into the development tool.

The HELIOS medical software engineering environment.

The aim of the HELIOS project is to create an integrated Software Engineering Environment (SEE) to facilitate the development and maintenance of medical applications. HELIOS is made of a set of software components, communicating through a software bus called the HELIOS Unification Bus. The object oriented paradigm is used both as the basic structure for building the software components and as the methodology for modelling, storing and retrieving the entities and procedures used in an application. Development standards include UNIX as operating system and X Window/MOTIF as windowing environment. One of the target applications for the HELIOS prototype is the development of a multimedia medical workstation as a front end to a hospital information system.

Generation-dependent control mechanisms in cell proliferation and differentiation--the power of two.

There is evidence that the proliferation of cells is controlled by the number of divisions after leaving a multi-potent (stem) cell. A detailed study of the growth of tissue in the small intestinal tract, more precisely the growth of crypts and villi, suggests that not only the proliferation but also the differentiation of cells obey the same biological law. We postulate a theory of a cellular internal control mechanism: the cell-generation control of differentiation and proliferation. This basic mechanism, together with external influences, determines the kinetic behaviour of the crypt-villus system.

Modelling and simulation of complex control structures in cell biology.

Biological and biomedical tissues and organs represent very complex and highly dynamic systems. The problem to model such complex systems is twofold. First, it is necessary to identify and describe the biological properties and the connecting control mechanisms of the studied system and its subparts. Here, biological knowledge is often missing. Secondly, we are confronted with the problem to formulate the model of the control structure in a form that allows model analysis. Here, a normal mathematical formalism is often inadequate. To solve these modelling problems and to develop methods for building models of complex control structures that will enable the formulation of dynamic systems in biology, a framework for building such models is presented. The model framework is here mainly used for studies of dynamic cell structures, but the possible application areas are more general. An example is given for modelling cell structures of epithelial tissues in the intestine.

The growth and life of a monoclonal crypt.

A computer simulation of a highly dynamic model for the birth, growth and adult life of a monoclonal crypt in the intestine was developed starting with a single precursor stem cell. The intestinal epithelial system was studied and observed in analogy to 'in vivo' experiments. The model output, e.g. the geometric shape of a crypt, mitotic index, labelling index and the crypt length distribution in adult state, was compared with experimental data. There was evidence from the simulation that a certain steady state in the adult life could be reached regardless of some harmless influences in post-natal life, e.g. the influence of being weaned or non-weaned. The model is based on our hypothesis of the generation-controlled proliferation mechanism and at the same time is a confirmation of it.

The cell cycle time in intestinal crypts by simulation of FLM experiments.

A computer program is developed that permits simulation of the dynamic behaviour of cells in intestinal crypts (Meinzer & Sandblad, 1985). Here we present the simulation of FLM data which is compared with the experimental findings of Al-Dewachi et al. (1974). The phase durations and total cycle times of cells in the jejunal crypts of rats were calculated. Additionally, the influence of various control parameters on the simulation output is discussed, e.g. the standard errors of phase times and the grain dilution at mitosis.

Evidence for cell generation controlled proliferation in the small intestinal crypt.

In this paper we discuss the hypothesis that cell proliferation is controlled by the number of generations after leaving an 'eternal' stem cell. The theory is based on a simulation of the kinetic behaviour of cells in the intestinal crypts. There is evidence of three, four and five generations of cells which are allowed to enter mitosis in the lower and upper part of the normal intestinal tract, and in some disease states, respectively. We suggest an internal proliferation control: some kind of knowledge that cells carry from generation to generation. It is an open question what sets and changes the generation counter: internal genetic information or external influences such as growth factors or chalones. The geometric shape of the epithelial tissue in the intestinal tract can be understood as the steady state of a highly dynamic process. Age and death are determined from the beginning; cell-cell interaction or communication is not necessary and can be neglected. Our theory will be illustrated using the intestinal crypts as they are easily accessible, of a simple structure and completely described in the literature.

A simulation model for studies of intestine cell dynamics.

A dynamic simulation model for the epithelial cell structures of the intestine has been developed. The model is based on hypotheses found in the literature. It is shown that basic cell dynamics can be reproduced by simulation experiments. The simulation program is designed so that model output comparable with experimental findings can be obtained. The use of a dynamic simulation model can be interpreted as a simulated experiment in vivo. The model therefore allows analysis of dynamic behaviour that cannot be performed by normal experimental work. This means that the model can be used as a tool for verification/falsification of hypotheses about dynamics in both normal and abnormal cell structures.

Data security in information systems by language analysis.

The paper describes how a language analyser (parser) is used as interface between a user and the functions of an information system. A specific user is at log-on forced into a sublanguage analyser, which only recognizes statements relevant to this specific user. Every attempt to use non-allowed functions is rejected, and the user is guided into his sublanguage. The language analyser is defined completely separately from the semantics of the information system, and it can be automatically generated outgoing from a definition of language functions.