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PubMed2006

Improving medical protocols by formal methods.

OBJECTIVES: During the last decade, evidence-based medicine has given rise to an increasing number of medical practice guidelines and protocols. However, the work done on developing and distributing protocols outweighs the efforts on guaranteeing their quality. Indeed, anomalies like ambiguity and incompleteness are frequent in medical protocols. Recent efforts have tried to address the problem of protocol improvement, but they are not sufficient since they rely on informal processes and notations. Our objective is to improve the quality of medical protocols. APPROACH: The solution we suggest to the problem of quality improvement of protocols consists in the utilisation of formal methods. It requires the definition of an adequate protocol representation language, the development of techniques for the formal analysis of protocols described in that language and, more importantly, the evaluation of the feasibility of the approach based on the formalisation and verification of real-life medical protocols. For the first two aspects we rely on earlier work from the fields of knowledge representation and formal methods. The third aspect, i.e. the evaluation of the use of formal methods in the quality improvement of protocols, constitutes our main objective. The steps with which we have carried out this evaluation are the following: (1) take two real-life reference protocols which cover a wide variety of protocol characteristics; (2) formalise these reference protocols; (3) check the formalisation for the verification of interesting protocol properties; and (4) determine how many errors can be uncovered in this way. RESULTS: Our main results are: a consolidated formal language to model medical practice protocols; two protocols, each both modelled and formalised; a list of properties that medical protocols should satisfy; verification proofs for these protocols and properties; and perspectives of the potentials of this approach. Our results have been evaluated by a panel of medical experts, who judged that the problems we detected in the protocols with the help of formal methods were serious and should be avoided. CONCLUSIONS: We have succeeded in demonstrating the feasibility of formal methods for improving medical protocols.

Artificial Intelligence↗
PubMed2005

Pathology data integration with eXtensible Markup Language.

It is impossible to overstate the importance of XML (eXtensible Markup Language) as a data organization tool. With XML, pathologists can annotate all of their data (clinical and anatomic) in a format that can transform every pathology report into a database, without compromising narrative structure. The purpose of this manuscript is to provide an overview of XML for pathologists. Examples will demonstrate how pathologists can use XML to annotate individual data elements and to structure reports in a common format that can be merged with other XML files or queried using standard XML tools. This manuscript gives pathologists a glimpse into how XML allows pathology data to be linked to other types of biomedical data and reduces our dependence on centralized proprietary databases.

Database Management Systems↗
PubMed2000

[Use of the ACSL simulation language for physiologic toxicokinetic models].

For the description of the processes of absorption, excretion or elimination of chemicals, the open one- or two-compartment models have been used thus far. The latter consist mainly of the fast (central) and slow (peripheral) compartments. The toxicological studies were based on an assumption that the organic processes develop according to is the first order kinetic reaction. However, the absorption, elimination or excretion of toxic chemicals are in fact much more complicated processes that should be explained using, e.g. the physiologically-based toxicokinetic (PBTK) models, covering physiological, biochemical and metabolic parameters, as well as the allometric calibration of selected parameters for interspecies extrapolations, and in vitro/in vivo extrapolations of metabolic parameters. Simulation languages, e.g. ACSL (Advanced Continuous Simulation Language) are indispensable application tools to be operated with PBTK models. They have been developed for modelling systems described by time-dependent non-linear differential equations and/or transfer functions. ACSL with its interfaces (ACSL Builder, ACSL Graphic Modeller, ACSL Math) ensures data input and communication inside the model by the control, transfer and computed parameters. The physiologically-based toxicokinetic models employ a large number of different parameters, which enables, e.g. forecasting the dose/effect or dose/response relationship absorption rate, metabolic pathways, excretion or elimination according to the absorbed dose of xenobiotic; evaluation of risk assessment; extrapolation from high to low doses characteristic of environmental exposure or setting biological exposure limits.

Body Fluid Compartments↗
PubMed1994

Simplified user poll and experience report language (SUPER): implementation and application.

Biological computing is generally organized as standalone implementation on a PC-type computer or on a central facility (e.g. a university computer center). Services provided by central facilities need to be tailored to the user community. Unless very work-intensive individual contacts are used, the feedback must be collected with generalized tools, such as questionnaires distributed in the form of a newsletter. We have developed a method to have such polls automated and tailored, as well as having multiple-choice questions combined with branching after fundamental questions. As the evaluation of the results needs to know the questions asked, we have also included a method to process the answers and give detailed tables on the answers. SUPER was applied in a poll to query the academic usership in Switzerland on the usage of molecular biology databases.

Biology↗
PubMed2005

ROCR: visualizing classifier performance in R.

UNLABELLED: ROCR is a package for evaluating and visualizing the performance of scoring classifiers in the statistical language R. It features over 25 performance measures that can be freely combined to create two-dimensional performance curves. Standard methods for investigating trade-offs between specific performance measures are available within a uniform framework, including receiver operating characteristic (ROC) graphs, precision/recall plots, lift charts and cost curves. ROCR integrates tightly with R's powerful graphics capabilities, thus allowing for highly adjustable plots. Being equipped with only three commands and reasonable default values for optional parameters, ROCR combines flexibility with ease of usage. AVAILABILITY: http://rocr.bioinf.mpi-sb.mpg.de. ROCR can be used under the terms of the GNU General Public License. Running within R, it is platform-independent. CONTACT: tobias.sing@mpi-sb.mpg.de.

Computer Graphics↗
PubMed2004

An XML standard for the dissemination of annotated 2D gel electrophoresis data complemented with mass spectrometry results.

BACKGROUND: Many proteomics initiatives require a seamless bioinformatics integration of a range of analytical steps between sample collection and systems modeling immediately assessable to the participants involved in the process. Proteomics profiling by 2D gel electrophoresis to the putative identification of differentially expressed proteins by comparison of mass spectrometry results with reference databases, includes many components of sample processing, not just analysis and interpretation, are regularly revisited and updated. In order for such updates and dissemination of data, a suitable data structure is needed. However, there are no such data structures currently available for the storing of data for multiple gels generated through a single proteomic experiments in a single XML file. This paper proposes a data structure based on XML standards to fill the void that exists between data generated by proteomics experiments and storing of data. RESULTS: In order to address the resulting procedural fluidity we have adopted and implemented a data model centered on the concept of annotated gel (AG) as the format for delivery and management of 2D Gel electrophoresis results. An eXtensible Markup Language (XML) schema is proposed to manage, analyze and disseminate annotated 2D Gel electrophoresis results. The structure of AG objects is formally represented using XML, resulting in the definition of the AGML syntax presented here. CONCLUSION: The proposed schema accommodates data on the electrophoresis results as well as the mass-spectrometry analysis of selected gel spots. A web-based software library is being developed to handle data storage, analysis and graphic representation. Computational tools described will be made available at http://bioinformatics.musc.edu/agml. Our development of AGML provides a simple data structure for storing 2D gel electrophoresis data.

Computational Biology↗
PubMed2000

Experience using a programmable rules engine to implement a complex medical protocol during order entry.

WizOrder, Vanderbilt University Medical Center's (VUMC) clinician order entry system, is an excellent platform for delivering high-quality decision support to clinical end-users. A scripting language designed to make it easy for non-programmer domain experts to enter rules helps distribute the generation and maintenance of the knowledge-base necessary to drive effective decision support. Domain-experts have used this system to successfully implement relatively simple protocols. The VUMC Care Improvement Committee identified diagnosis of and treatment for suspected or confirmed deep venous thrombosis or pulmonary embolism as an area where decision-support could improve clinician compliance with established evidence-based protocols. The authors describe our experience with using our existing scripting system to implement decision support for a complex medical protocol.

Clinical Protocols↗
PubMed1994

Simplified user poll and experience report language (SUPER): implementation and application.

Biological computing is generally organized as stand-alone implementation on a PC-type computer or on a central facility (e.g. a university computer center). Services provided by central facilities need to be tailored to the user community. Unless very work-intensive individual contacts are used, the feedback must be collected with generalized tools, such as questionnaires distributed in the form of a newsletter. We have developed a method to have such polls automated and tailored, as well as having multiple-choice questions combined with branching after fundamental questions. As the evaluation of the results needs to know the questions asked, we have also included a method to process the answers and give detailed tables on the answers. SUPER was applied in a poll to query the academic usership in Switzerland on the usage of molecular biology databases.

Evaluation Studies as Topic↗
PubMed2005

Computer language for identifying chemicals with comprehensive two-dimensional gas chromatography and mass spectrometry.

This paper describes a language for expressing criteria for chemical identification with comprehensive two-dimensional gas chromatography paired with mass spectrometry (GC x GC-MS) and presents computer-based tools implementing the language. The Computer Language for Indentifying Chemicals (CLIC) allows expressions that describe rules (or constraints) for selecting chemical peaks or data points based on multi-dimensional chromatographic properties and mass spectral characteristics. CLIC offers chromatographic functions of retention times, functions of mass spectra, numbers for quantitative and relational evaluation, and logical and arithmetic operators. The language is demonstrated with the compound-class selection rules described by Welthagen et al. [W. Welthagen, J. Schnelle-Kreis, R. Zimmermann, J. Chromatogr. A 1019 (2003) 233-249]. A software implementation of CLIC provides a calculator-like graphical user-interface (GUI) for building and applying selection expressions. From the selection calculator, expressions can be used to select chromatographic peaks that meet the criteria or create selection chromatograms that mask data points inconsistent with the criteria. Selection expressions can be combined with graphical, geometric constraints in the retention-time plane as a powerful component for chemical identification with template matching or used to speed and improve mass spectrum library searches.

Gas Chromatography-Mass Spectrometry↗
PubMed2002

Clinical data retrieval: 25 years of temporal query management at the University of Vienna Medical School.

OBJECTIVES: Today, many clinical information systems include analysis components which allow clinicians to apply a selection of predefined statistical functions that satisfy typical cases. They are mostly to inflexible to handle complex, non-standard problems, however. The focus of this paper, therefore, is to present an approach that enables clinicians to autonomously create ad hoc queries including temporal relations in an interactive environment. METHODS: We developed the query language AMAS, which was specifically customized for users from the medical domain to flexibly retrieve and interpret temporal, clinical data. AMAS provides for a significant temporal expressiveness in data retrieval using time-stamped clinical databases and relies on an operator-operand concept for the specification of a query. RESULTS: Within the last 25 years, four different clinical retrieval systems have been implemented at the Department of Medical Computer Sciences, based on the AMAS query language. Currently, these systems allow access to the medical records of more than 2 million patients. Physicians of 46 different departments at the University of Vienna and Graz Medical Schools have made extensive use of these systems in the course of clinical research and patient care, executing more than 10,000 queries per year. CONCLUSIONS: We discuss a list of 20 issues that represent the most essential lessons we have learned in the development of the four systems mentioned above. Amongst others, our experiences indicate that the operator-operand concept allows on intuitive specification of complex, temporal queries. Further, customization to different user classes, based on their statistical background, is essential.

Austria↗
PubMed2003

The latest MML (Medical Markup Language) version 2.3--XML-based standard for medical data exchange/storage.

As a set of standards, Medical Markup Language (MML) has been developed over the last 8 years to allow the exchange of medical data between different medical information providers MML version 2.21 was characterized by XML as metalanguage and was announced in 1999, at which time full-scale implementation tests were carried out; subsequently, various information and functional inadequacies were discovered in this version. MML was therefore updated to version 2.3 in 2001. At present, MML contains 12 MML modules including the new referral, test result, and report modules. In version 2.3, the group ID element was added; the access right definition and health insurance module were amended.

Humans↗
PubMed2005

The tissue microarray data exchange specification: a document type definition to validate and enhance XML data.

BACKGROUND: The Association for Pathology Informatics (API) Extensible Mark-up Language (XML) TMA Data Exchange Specification (TMA DES) proposed in April 2003 provides a community-based, open source tool for sharing tissue microarray (TMA) data in a common format. Each tissue core within an array has separate data including digital images; therefore an organized, common approach to produce, navigate and publish such data facilitates viewing, sharing and merging TMA data from different laboratories. The AIDS and Cancer Specimen Resource (ACSR) is a HIV/AIDS tissue bank consortium sponsored by the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis (DCTD). The ACSR offers HIV-related malignancies and uninfected control tissues in microarrays (TMA) accompanied by de-identified clinical data to approved researchers. Exporting our TMA data into the proposed API specified format offers an opportunity to evaluate the API specification in an applied setting and to explore its usefulness. RESULTS: A document type definition (DTD) that governs the allowed common data elements (CDE) in TMA DES export XML files was written, tested and evolved and is in routine use by the ACSR. This DTD defines TMA DES CDEs which are implemented in an external file that can be supplemented by internal DTD extensions for locally defined TMA data elements (LDE). CONCLUSION: ACSR implementation of the TMA DES demonstrated the utility of the specification and allowed application of a DTD to validate the language of the API specified XML elements and to identify possible enhancements within our TMA data management application. Improvements to the specification have additionally been suggested by our experience in importing other institution's exported TMA data. Enhancements to TMA DES to remove ambiguous situations and clarify the data should be considered. Better specified identifiers and hierarchical relationships will make automatic use of the data possible. Our tool can be used to reorder data and add identifiers; upgrading data for changes in the specification can be automatically accomplished. Using a DTD (optionally reflecting our proposed enhancements) can provide stronger validation of exported TMA data.

AIDS-Related Complex↗
PubMed2000

Automating parallel implementation of neural learning algorithms.

Neural learning algorithms generally involve a number of identical processing units, which are fully or partially connected, and involve an update function, such as a ramp, a sigmoid or a Gaussian function for instance. Some variations also exist, where units can be heterogeneous, or where an alternative update technique is employed, such as a pulse stream generator. Associated with connections are numerical values that must be adjusted using a learning rule, and and dictated by parameters that are learning rule specific, such as momentum, a learning rate, a temperature, amongst others. Usually, neural learning algorithms involve local updates, and a global interaction between units is often discouraged, except in instances where units are fully connected, or involve synchronous updates. In all of these instances, concurrency within a neural algorithm cannot be fully exploited without a suitable implementation strategy. A design scheme is described for translating a neural learning algorithm from inception to implementation on a parallel machine using PVM or MPI libraries, or onto programmable logic such as FPGAs. A designer must first describe the algorithm using a specialised Neural Language, from which a Petri net (PN) model is constructed automatically for verification, and building a performance model. The PN model can be used to study issues such as synchronisation points, resource sharing and concurrency within a learning rule. Specialised constructs are provided to enable a designer to express various aspects of a learning rule, such as the number and connectivity of neural nodes, the interconnection strategies, and information flows required by the learning algorithm. A scheduling and mapping strategy is then used to translate this PN model onto a multiprocessor template. We demonstrate our technique using a Kohonen and backpropagation learning rules, implemented on a loosely coupled workstation cluster, and a dedicated parallel machine, with PVM libraries.

Algorithms↗
PubMed2005

Manuscript Architect: a Web application for scientific writing in virtual interdisciplinary groups.

BACKGROUND: Although scientific writing plays a central role in the communication of clinical research findings and consumes a significant amount of time from clinical researchers, few Web applications have been designed to systematically improve the writing process. This application had as its main objective the separation of the multiple tasks associated with scientific writing into smaller components. It was also aimed at providing a mechanism where sections of the manuscript (text blocks) could be assigned to different specialists. Manuscript Architect was built using Java language in conjunction with the classic lifecycle development method. The interface was designed for simplicity and economy of movements. Manuscripts are divided into multiple text blocks that can be assigned to different co-authors by the first author. Each text block contains notes to guide co-authors regarding the central focus of each text block, previous examples, and an additional field for translation when the initial text is written in a language different from the one used by the target journal. Usability was evaluated using formal usability tests and field observations. RESULTS: The application presented excellent usability and integration with the regular writing habits of experienced researchers. Workshops were developed to train novice researchers, presenting an accelerated learning curve. The application has been used in over 20 different scientific articles and grant proposals. CONCLUSION: The current version of Manuscript Architect has proven to be very useful in the writing of multiple scientific texts, suggesting that virtual writing by interdisciplinary groups is an effective manner of scientific writing when interdisciplinary work is required.

Authorship↗
PubMed2006

ClaML: a standard for the electronic publication of classification coding schemes.

This paper proposes a number of revisions to CEN/TS 14463 (ClaML), which is a pre-standard mark-up language for the electronic publication of classification coding schemes. A CEN Taskforce in close collaboration with the WHO network carefully analysed 70 classifications from the healthcare domain. All were transformed in ClaML using a dedicated classification management tool. The proposal removes all formatting elements and adds a number of layout structuring elements. Several elements have been replaced by attributes to enforce internal consistency. A modest number of extensions are proposed to help users and authors in maintenance and version control. A pilot implementation has shown that ICD10 as one of the most complex traditional classifications can be adequately represented to produce quality printed output.

Forms and Records Control↗
PubMed2005

simuPOP: a forward-time population genetics simulation environment.

SUMMARY: simuPOP is a forward-time population genetics simulation environment. The core of simuPOP is a scripting language (Python) that provides a large number of objects and functions to manipulate populations, and a mechanism to evolve populations forward in time. Using this R/Splus-like environment, users can create, manipulate and evolve populations interactively, or write a script and run it as a batch file. Owing to its flexible and extensible design, simuPOP can simulate large and complex evolutionary processes with ease. At a more user-friendly level, simuPOP provides an increasing number of built-in scripts that perform simulations ranging from implementation of basic population genetics models to generating datasets under complex evolutionary scenarios. AVAILABILITY: simuPOP is freely available at http://simupop.sourceforge.net, distributed under GPL license.

Algorithms↗
PubMed1994

Writing Arden Syntax Medical Logic Modules.

The Arden Syntax for Medical Logic Modules is a language for encoding medical knowledge bases that consist of independent modules. The Arden Syntax has been used to generate clinical alerts, diagnostic interpretations, management messages, and screening for research studies and quality assurance. An Arden Syntax knowledge base consists of rules called Medical Logic Modules (MLMs), which are stored as simple ASCII files that can be written on any text editor. An MLM is made of slots grouped into three categories: maintenance information, library information, and the actual medical knowledge. Most MLMs are triggered by clinical events, evaluate medical criteria, and, if appropriate, perform an action such as sending a message to a health care provider. This paper provides a detailed tutorial on how to write MLMs.

Artificial Intelligence↗
PubMed1999

Optimizing healthcare research data warehouse design through past COSTAR query analysis.

Over the past two years we have reviewed and implemented the specifications for a large relational database (a data warehouse) to find research cohorts from data similar to that contained within the clinical COSTAR database at the Massachusetts General Hospital. A review of 16 years of COSTAR research queries was conducted to determine the most common search strategies. These search strategies are relevant to the general research community, because they use the Medical Query Language (MQL) developed for the COSTAR M database which is extremely flexible (much more so than SQL) and allows searches by coded fields, text reports, and laboratory values in a completely ad hoc fashion. By reviewing these search strategies, we were able to obtain user specifications for a research oriented healthcare data warehouse that could support 90% of the queries. The data warehouse was implemented in a relational database using the star schema, allowing for highly optimized analytical processing. This allowed queries that performed slowly in the M database to be performed very rapidly in the relational database. It also allowed the data warehouse to scale effectively.

Databases as Topic↗