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Using the extensible markup language (XML) in automated clinical practice guidelines.

Much work has been done in the area of web-based clinical practice guidelines. Issues such as representation, description, architectures, and implementation have been explored previously. Most if not all of these web-based applications rely exclusively on HTML, the HyperText Markup Language. In the process of prototyping a guideline service to be used in a diabetes operations improvement project, we developed a model for a guideline engine that makes use of the Extensible Markup Language (XML), both as an interface to the engine and as a vehicle for delivering structured guideline content. We feel that XML may offer advantages in implementing guideline services that are difficult (if not impossible) to accomplish with HTML alone.

Computer Systems↗

Relative survival analysis in R.

Relative survival techniques are used to compare the survival experience in a study cohort with the one expected should they follow the background population mortality rates. The techniques are especially useful when the cause-specific death information is not accurate or not available since they provide a measure of excess mortality in a group of patients with a certain disease. There are several approaches to modeling relative survival, but there is no widely used statistical package that would incorporate the relevant techniques. The existing software was mostly written by the authors of different methods, in different computer languages and with different requirements for the data input, which makes it almost impossible for a user to choose between available models. We describe our R package relsurv that provides functions for easy and flexible fitting of several relative survival regression models.

Cohort Studies↗

Representation and simulation of biochemical processes using the pi-calculus process algebra.

Despite the rapidly accumulating body of knowledge about protein networks, there is currently no convenient way of sharing and manipulation of such information. We suggest that a formal computer language for describing the biomolecular processes underlying protein networks is essential for rapid advancement in this field. We propose to model biomolecular processes by using the pi-Calculus, a process algebra, originally developed for describing computer processes. Our model for biochemical processes is mathematically well-defined, while remaining biologically faithful and transparent. It is amenable to computer simulation, analysis and formal verification. We have developed a computer simulation system, the PiFCP, for execution and analysis of pi-calculus programs. The system allows us to trace, debug and monitor the behavior of biochemical networks under various manipulations. We present a pi-calculus model for the RTK-MAPK signal transduction pathway, formally represent detailed molecular and biochemical information, and study it by various PiFCP simulations.

Biochemistry↗

ProML--the protein markup language for specification of protein sequences, structures and families.

We propose a specification language ProML for protein sequences, structures, and families based on the open XML standard. The language allows for portable, system-independent, machine-parsable and human-readable representation of essential features of proteins. The language is of immediate use for several bioinformatics applications: we discuss clustering of proteins into families and the representation of the specific shared features of the respective clusters. Moreover, we use ProML for specification of data used in fold recognition bench-marks exploiting experimentally derived distance constraints.

Programming Languages↗

The development of variable MLM editor and TSQL translator based on Arden Syntax in Taiwan.

The Arden Syntax standard has been utilized in the medical informatics community in several countries during the past decade. It is never used in nursing in Taiwan. We try to develop a system that acquire medical expert knowledge in Chinese and translates data and logic slot into TSQL Language. The system implements TSQL translator interpreting database queries referred to in the knowledge modules. The decision-support systems in medicine are data driven system where TSQL triggers as inference engine can be used to facilitate linking to a database.

Artificial Intelligence↗

Generating interactive molecular documentaries using a library of graphical actions.

Paper-based publishing of scientific articles limits the types of presentations that can be used. The emergence of electronic publishing has created opportunities to increase the range of formats available for conveying scientific content. We introduce the Graphical Explanation Markup Language, GEML, implemented as an XML format for defining molecular documentaries which exploit the interactive capabilities of electronic publishing. GEML builds upon existing molecular structure definitions such as the Protein Data Bank (PDB) standard file format. GEML provides a library of gestures (or actions) commonly used for structural explanations, and is extensible. XML allows us to separate explicit statements about how to highlight a molecular structure from the implementation of these instructions. We also present GEIS (Generator of Explanatory Interactive Systems), a program that takes as input a GEML documentary definition file and produces all the files necessary for an interactive, web-based molecular documentary. To demonstrate GEML and GEIS, we constructed a documentary capturing the difficult 3D notions expressed in two selected published reports about human topoisomerase I. We have created a prototype Java application, GEMLBuilder, as an editor of GEML files.

Computer Graphics↗

The Sophus anaesthesia simulator v. 2.0. A Windows 95 control-center of a full-scale simulator.

The Sophus group was founded in Denmark in 1992 with the aims of doing research into human error in anaesthesiology. Development of a simulation-environment was seen as one of the tools for research and training. This article describes the PC user interface of the SOPHUS anaesthesia simulator, SOPHUS v. 2.0 for Windows 95, and the script language, SASL v. 1.2. The script language provides possibilities of making scenarios, which develop in different directions according to the treatment of the patient by means of IF/THEN-statements, loops etc.

Anesthesiology↗

Improving interorganizational data interchange for drug development.

This paper presents a reengineered process that uses a markup language to do interorganizational data interchange between the participants in the US drug development process. The two major goals of this paper are to present (1) a detailed enough description of the reengineered version of this process that a practitioner will be able to use it and (2) a case-study of the reengineering of an interorganizational data interchange system that is applicable to other areas in health care. The detailed description is augmented with a companion web-site that shows all programs in a working prototype. The case-study uses an IDEF0 model to show the structure of benefits from markup standards for interorganizational data interchange.

Computer Communication Networks↗

SRS--an indexing and retrieval tool for flat file data libraries.

SRS (Sequence Retrieval System) is an information indexing and retrieval system designed for libraries with a flat file format such as the EMBL nucleotide sequence databank, the SwissProt protein sequence databank or the Prosite library of protein subsequence consensus patterns. SRS supports the data structure of these libraries by providing special indices for implementing lists of subentities (e.g. feature tables) or hierarchically structured data-fields (e.g. taxonomic classification). A language (ODD) has been designed for the convenient specification of library format and organization, representation of individual data-fields within the system (design of indices) and structuring other data needed during retrieval. This ensures flexibility required for coping with different library formats, which are subject to continuous change. Queries and inspection of retrieved entries can be performed from a user interface with pull-down menus and windows. SRS supports various input and output formats but is particularly well adapted to the GCG programs.

Abstracting and Indexing↗

The carbohydrate sequence markup language (CabosML): an XML description of carbohydrate structures.

UNLABELLED: Bioinformatics resources for glycomics are very poor as compared with those for genomics and proteomics. The complexity of carbohydrate sequences makes it difficult to define a common language to represent them, and the development of bioinformatics tools for glycomics has not progressed. In this study, we developed a carbohydrate sequence markup language (CabosML), an XML description of carbohydrate structures. AVAILABILITY: The language definition (XML Schema) and an experimental database of carbohydrate structures using an XML database management system are available at http://www.phoenix.hydra.mki.co.jp/CabosDemo.html CONTACT: kikuchi@hydra.mki.co.jp.

Carbohydrate Sequence↗

Detecting clusters of different geometrical shapes in microarray gene expression data.

MOTIVATION: Clustering has been used as a popular technique for finding groups of genes that show similar expression patterns under multiple experimental conditions. Many clustering methods have been proposed for clustering gene-expression data, including the hierarchical clustering, k-means clustering and self-organizing map (SOM). However, the conventional methods are limited to identify different shapes of clusters because they use a fixed distance norm when calculating the distance between genes. The fixed distance norm imposes a fixed geometrical shape on the clusters regardless of the actual data distribution. Thus, different distance norms are required for handling the different shapes of clusters. RESULTS: We present the Gustafson-Kessel (GK) clustering method for microarray gene-expression data. To detect clusters of different shapes in a dataset, we use an adaptive distance norm that is calculated by a fuzzy covariance matrix (F) of each cluster in which the eigenstructure of F is used as an indicator of the shape of the cluster. Moreover, the GK method is less prone to falling into local minima than the k-means and SOM because it makes decisions through the use of membership degrees of a gene to clusters. The algorithmic procedure is accomplished by the alternating optimization technique, which iteratively improves a sequence of sets of clusters until no further improvement is possible. To test the performance of the GK method, we applied the GK method and well-known conventional methods to three recently published yeast datasets, and compared the performance of each method using the Saccharomyces Genome Database annotations. The clustering results of the GK method are more significantly relevant to the biological annotations than those of the other methods, demonstrating its effectiveness and potential for clustering gene-expression data. AVAILABILITY: The software was developed using Java language, and can be executed on the platforms that JVM (Java Virtual Machine) is running. It is available from the authors upon request. SUPPLEMENTARY INFORMATION: Supplementary data are available at http://dragon.kaist.ac.kr/gk.

Algorithms↗

An interlingua for electronic interchange of medical information: using frames to map between clinical vocabularies.

The proliferation of medical knowledge has led to the development of extensive dictionaries for electronically accessing information resources. The task of standardizing terminology used for electronic hospital records and for knowledge bases for medical expert systems and indexing the medical literature cannot easily be met by developing a single, monolithic "official" medical vocabulary. Developing a monolithic vocabulary would require a massive effort, and its existence would not guarantee its use by third-party payors, by practicing clinicians, or by developers of electronic medical information systems. Recognizing this, the National Library of Medicine (NLM) has begun to develop the Unified Medical Language System (UMLS) as a means of promoting electronic information exchange among systems with controlled vocabularies. The authors describe a frame-based system developed as an experimental approach to mapping between controlled clinical vocabularies.

Cluster Analysis↗

Effects of treatment on linguistic and social skills in toddlers with delayed language development.

This study investigated the effects of early language intervention on various linguistic and social skills of late-talking toddlers. The 21 children who participated in the investigation were randomly assigned to an experimental group (n = 11) or a control (delayed-treatment) group (n = 10). The experimental group participated in a 12-week clinician-implemented language intervention program. Groups were compared at pretest and posttest on five linguistic variables: Mean Length of Utterance, Total Number of Words, Number of Different Words, Lexical Repertoire, and Percentage of Intelligible Utterances, as well as on Socialization and Parental Stress. Significant group differences were found for each of the variables, indicating facilitative effects of the treatment. Notably, increases were observed in areas that were not specifically targeted by the intervention. Implications of these results are discussed with respect to considerations regarding clinical management decisions for toddlers with delayed language development.

Child Language↗

A basis for a visual language for describing, archiving and analyzing functional models of complex biological systems.

BACKGROUND: We propose that a computerized, internet-based graphical description language for systems biology will be essential for describing, archiving and analyzing complex problems of biological function in health and disease. RESULTS: We outline here a conceptual basis for designing such a language and describe BioD, a prototype language that we have used to explore the utility and feasibility of this approach to functional biology. Using example models, we demonstrate that a rather limited lexicon of icons and arrows suffices to describe complex cell-biological systems as discrete models that can be posted and linked on the internet. CONCLUSIONS: Given available computer and internet technology, BioD may be implemented as an extensible, multidisciplinary language that can be used to archive functional systems knowledge and be extended to support both qualitative and quantitative functional analysis.

Animals↗

The UMLS Semantic Network and the Semantic Web.

The Unified Medical Language System is an extensive source of biomedical knowledge developed and maintained by the US National Library of Medicine (NLM) and is being currently used in a wide variety of biomedical applications. The Semantic Network, a component of the UMLS is a structured description of core biomedical knowledge consisting of well defined semantic types and relationships between them. We investigate the expressiveness of DAML+OIL, a markup language proposed for ontologies on the Semantic Web, for representing the knowledge contained in the Semantic Network. Requirements specific to the Semantic Network, such as polymorphic relationships and blocking relationship inheritance are discussed and approaches to represent these in DAML+OIL are presented. Finally, conclusions are presented along with a discussion of ongoing and future work.

Programming Languages↗

Using the Unified Modelling Language (UML) to guide the systemic description of biological processes and systems.

One of the main issues in Systems Biology is to deal with semantic data integration. Previously, we examined the requirements for a reference conceptual model to guide semantic integration based on the systemic principles. In the present paper, we examine the usefulness of the Unified Modelling Language (UML) to describe and specify biological systems and processes. This makes unambiguous representations of biological systems, which would be suitable for translation into mathematical and computational formalisms, enabling analysis, simulation and prediction of these systems behaviours.

Epigenesis, Genetic↗

Knowledge-based verification of clinical guidelines by detection of anomalies.

As shown in numerous studies, a significant part of published clinical guidelines is tainted with different types of semantical errors that interfere with their practical application. The adaptation of generic guidelines, necessitated by circumstances such as resource limitations within the applying organization or unexpected events arising in the course of patient care, further promotes the introduction of defects. Still, most current approaches for the automation of clinical guidelines are lacking mechanisms, which check the overall correctness of their output. In the domain of software engineering in general and in the domain of knowledge-based systems (KBS) in particular, a common strategy to examine a system for potential defects consists in its verification. The focus of this work is to present an approach, which helps to ensure the semantical correctness of clinical guidelines in a three-step process. We use a particular guideline specification language called Asbru to demonstrate our verification mechanism. A scenario-based evaluation of our method is provided based on a guideline for the artificial ventilation of newborn infants. The described approach is kept sufficiently general in order to allow its application to several other guideline representation formats.

Artificial Intelligence↗

Towards health care process description framework: an XML DTD design.

The development of health care and hospital information systems has to meet users needs as well as requirements such as the tracking of all care activities and the support of quality improvement. The use of process-oriented analysis is of-value to provide analysts with: (i) a systematic description of activities; (ii) the elicitation of the useful data to perform and record care tasks; (iii) the selection of relevant decision-making support. But paper-based tools are not a very suitable way to manage and share the documentation produced during this step. The purpose of this work is to propose a method to implement the results of process analysis according to XML techniques (eXtensible Markup Language). It is based on the IDEF0 activity modeling language (Integration DEfinition for Function modeling). A hierarchical description of a process and its components has been defined through a flat XML file with a grammar of proper metadata tags. Perspectives of this method are discussed.

Blood Transfusion↗