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Biomedical subjects

P Tarczy-Hornoch

Publications and source records attributed to P Tarczy-Hornoch.

At least 19 recordsLinked to original sources

BioMediator data integration: beyond genomics to neuroscience data.

The BioMediator system developed at the University of Washington (UW) provides a theoretical and practical foundation for data integration across diverse biomedical research domains and various data types. In this paper we demonstrate the generalizability of its architecture through its application to the UW Human Brain Project (HBP) for understanding language organization in the brain. We first describe the system architecture and the characteristics of the four data sources developed by the UW HBP. Second we present the process of developing the application prototype for HBP neuroscience researchers posing queries across these semantically and syntactically heterogeneous neurophysiologic data sources. Then we discuss the benefits and potential limitations of the BioMediator system as a general data integration solution for different user groups in genomic and neuroscience research domains.

Brain↗

A pilot bridging data integration and analytics: BioMediator and R?

Biological research today involves aggregating and analyzing large amounts of data from disparate sources. Tools such as the University of Washington's BioMediator system integrate heterogeneous data. Analytic packages such as the R environment have a rich set of tools to analyze biomedical research data. Our pilot project bridged data integration and analytics in a general way by successfully incorporating the BioMediator system into the R platform for specific analyses on neurophysiologic research data.

Brain↗

Integration of data for gene annotation using the BioMediator system.

Gene annotation requires integration of data from multiple sources in order to functionally classify genes. We are using BioMediator, a general purpose data-integration solution, to develop a gene annotation system to automate the process of collecting data from disparate genomic databases. Integration of annotation data from multiple sources into a single format will facilitate use of analytic tools for the proper functional classification of genes.

Base Sequence↗

Expression array annotation using the BioMediator biological data integration system and the BioConductor analytic platform.

This paper presents the implementation of a model for expression array annotation (EAA) using the BioMediator biological data integration system along with BioConductor, an analytic tools platform. The model presented addresses the need for annotation sources identified during BioConductor inverted exclamation mark s development. Annotation provides us with well-curated genomic background knowledge for expression array analysis and interpretation. Annotation requests are constructed and posted to the query interface of the EAA package (the EAA model implemented as a component of BioConductor). The software enumerates all possible annotation paths for queries. These are then transformed to PQL queries and processed by BioMediator. Annotation entities returned from the EAA package answer the annotation request.

Computational Biology↗

Implementation of a classification hierarchy for the GeneTests/GeneClinics genetic testing databases.

The combination of a) our changing understanding of genotypic and phenotypic classification of diseases and b) the rapid growth and expansion of the number of entries in two databases targeted toward clinicians resulted in the need to develop a flexible dynamic hierarchical classification system for genetic disorders. The two databases making use of this classification schemas are the GeneClinics (GC) database - www.geneclinics.org and the GeneTests (GT) database - www.genetests.org The GC and GT databases serve respsectively as the users manual and yellow pages of genetic testing. The GeneTests/GeneClinics (GT/GC) classification hierarchy is maintained as a simple set of parent/child relationships in a relational database. The hierarchy is generated in real time in response to a user request. It is not maintained as a set of members with relationships defined by characters that are parsed to determine the structure of the tree. The GT/GC classification hierarchy entries are handled as objects by the data maintenance and search tools and may have a number of attributes and associations that create a rich tool for defining and examining genetic disorders

Databases, Genetic↗

PQL: a declarative query language over dynamic biological schemata.

We introduce the PQL query language (PQL) used in the GeneSeek genetic data integration project. PQL incorporates many features of query languages for semi-structured data. To this we add the ability to express metadata constraints like intended semantics and database curation approach. These constraints guide the dynamic generation of potential query plans. This allows a single query to remain relevant even in the presence of source and mediated schemas that are continually evolving, as is often the case in data integration.

Computational Biology↗

A rule driven bi-directional translation system for remapping queries and result sets between a mediated schema and heterogeneous data sources.

As the number of online biomedical data sources increases, so too do the number of ways to access such data. The research described herein focuses on creating a data access system that provides bi-directional translation and mapping of data between heterogeneous databases and a mediated schema. Semantic mapping rules stored in a knowledge base are used by our generalized software to convert XML query results obtained from each data source to a common schema representing a single ontology. We apply this approach to the domain of online genetic databases, demonstrating the system's scalability and integratability.

Databases as Topic↗

Amniotic fluid infection, cytokines, and adverse outcome among infants at 34 weeks' gestation or less.

OBJECTIVE: We examined the hypothesis that amniotic fluid (AF) infection and elevated cytokine concentrations may cause neonatal injury beyond that expected solely from prematurity. METHODS: The effects of exposure to AF infection and elevated cytokine concentrations were measured in 151 infants born to afebrile women in preterm labor with intact membranes at less than or equal to 34 weeks' gestation. Amniotic fluid was collected by amniocentesis for culture and determination of tumor necrosis factor-alpha and interleukin-6. Cytokine concentrations, stratified by AF infection, were compared for three gestational age groups. We then examined the associations between a positive AF culture or elevated AF tumor necrosis factor-alpha concentration and adverse neonatal outcomes, adjusted for birth weight. RESULTS: Amniotic fluid from 45 (30%) of 151 pregnancies had microorganisms, an elevated tumor necrosis factor-alpha concentration, or both. Amniotic fluid cytokine concentrations were significantly higher among women in preterm labor at less than or equal to 30 weeks, compared with 31-34 weeks. Nine of 11 infants who died at less than or equal to 24 hours of age had AF infection or elevated AF tumor necrosis factor-alpha. For the 140 surviving infants, AF infection and/or an elevated AF tumor necrosis factor-alpha was associated with respiratory distress syndrome (adjusted odds ratio [OR] 1.7), grade 3-4 intraventricular hemorrhage (adjusted OR 2.2), necrotizing enterocolitis (adjusted OR 1.8), and multiple organ dysfunction (adjusted OR 3.0). CONCLUSION: Among infants born at less than or equal to 34 weeks to women who have intact membranes and are initially afebrile, those exposed to AF bacteria or cytokines have more adverse neonatal outcomes than unexposed infants of similar birth weight.

Adolescent↗

Development of a Personal Digital Assistant (PDA) based client/server NICU patient data and charting system.

Personal Digital Assistants (PDAs) offer clinicians the ability to enter and manage critical information at the point of care. Although PDAs have always been designed to be intuitive and easy to use, recent advances in technology have made them even more accessible. The ability to link data on a PDA (client) to a central database (server) allows for near-unlimited potential in developing point of care applications and systems for patient data management. Although many stand-alone systems exist for PDAs, none are designed to work in an integrated client/server environment. This paper describes the design, software and hardware selection, and preliminary testing of a PDA based patient data and charting system for use in the University of Washington Neonatal Intensive Care Unit (NICU). This system will be the subject of a subsequent study to determine its impact on patient outcomes and clinician efficiency.

Hospital Information Systems↗

A model for data integration systems of biomedical data applied to online genetic databases.

We present a general model for data integration systems using a mediated schema to represent commonalities in the underlying sources. These sources are mapped to the mediated schema using source descriptions. Users can pose queries against the mediated schema, allowing the system to generate automatically a query plan that enumerates and ranks all possible ways in which the query could be answered. We apply this approach to the domain of online genetic databases, demonstrating the system s ability to answer relevant queries across multiple sources.

Databases, Genetic↗

Gravitational effects on volume distribution in a model of partial and total liquid ventilation.

To estimate regional lung volume during ventilation with liquids (e. g. perfluorochemicals, PFC) we developed a multi-compartment mathematical model of a lung and thorax. The height of the fluid column and the fluid's density determine alveolar pressure (PA). The weight of thoracic contents above any given gravitational plane influences pleural pressure (PPL). Transpulmonary pressure (PTP=PA−PPL) and compliance of the lung and chest wall permit estimation of volumes. The results indicate the lung inflates almost uniformly during total liquid ventilation despite a substantial vertical PA gradient. Inflation uniformity is due to the offsetting vertical PPL gradient created by the added weight of the PFC and sustained by the relative rigidity of the chest wall. During partial liquid ventilation our model indicates that the combination of uniform PA with a large vertical gradient in PPL leads to a vertical PTP gradient and therefore relative over-inflation of the top of the lung. This effect increases with increasing PFC dose and with lung height.

Functional Residual Capacity↗

An evaluation of ontology exchange languages for bioinformatics.

Ontologies are specifications of the concepts in a given field, and of the relationships among those concepts. The development of ontologies for molecular-biology information and the sharing of those ontologies within the bioinformatics community are central problems in bioinformatics. If the bioinformatics community is to share ontologies effectively, ontologies must be exchanged in a form that uses standardized syntax and semantics. This paper reports on an effort among the authors to evaluate alternative ontology-exchange languages, and to recommend one or more languages for use within the larger bioinformatics community. The study selected a set of candidate languages, and defined a set of capabilities that the ideal ontology-exchange language should satisfy. The study scored the languages according to the degree to which they satisfied each capability. In addition, the authors performed several ontology-exchange experiments with the two languages that received the highest scores: OML and Ontolingua. The result of those experiments, and the main conclusion of this study, was that the frame-based semantic model of Ontolingua is preferable to the conceptual graph model of OML, but that the XML-based syntax of OML is preferable to the Lisp-based syntax of Ontolingua.

Computational Biology↗

Integrating knowledge resources at the point of care: opportunities for librarians.

Health sciences librarians at the University of Washington (UW) are partners in the evolution of Internet-based clinical information systems for two medical centers, University of Washington Medical Center and Harborview Medical Center, as well as the UW Primary Care Network clinics. Librarians lead information resource and systems development projects and play a variety of roles including facilitator, publisher, integrator, and educator. These efforts have been coordinated with parallel development efforts by the Integrated Advanced Information Management Systems (IAIMS) clinical informatics group in developing electronic medical record systems and clinical decision support tools. The outcome is MINDscape, a very heavily used Web view of the patient medical record with tightly integrated knowledge resources as well as numerous Web-accessible information resources and tools. The goal of this article is to provide a case study of librarian involvement in institutional information systems development at UW and to illustrate the variety of roles that librarians can assume in hospital settings.

Computer Systems↗

Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ.

Treatments available to improve compliance in surfactant-deficient states include exogenous surfactant (ES) and either partial (PLV) or total liquid ventilation (TLV) with perfluorochemical (PFC). Because of the additional air-lung and air-PFC interfaces introduced during PLV compared with TLV, we hypothesized that compliance would be worse during PLV than during TLV. Because surfactant is able to reduce interfacial tension between air and lung as well as between PFC and lung, we further hypothesized that compliance would improve with surfactant treatment before PLV. In excised preterm lamb lungs, we used Survanta for surfactant replacement and perflubron as the PFC. Compliance during PLV was intermediate between TLV and gas inflation, both with and without surfactant. Surfactant improved compliance during PLV, compared with PLV alone. Because of the force-balance equation governing the behavior of immiscible droplets on liquid surfaces, we predict that PFC droplets spread during PLV to cover the alveolar surface in surfactant-deficient lungs during most of lung inflation and deflation but that the PFC would retract into droplets in surfactant-sufficient lungs, except at end inspiration.

Animals↗

Creation and maintenance of Helix, a Web based database of medical genetics laboratories, to serve the needs of the genetics community.

Helix (healthlinks.washington.edu/helix) is a web accessible database that serves as the main U.S. directory of laboratories offering genetic testing. The database was designed to address the previously unmet need for a centralized, continuously updated source of information about clinical and research genetic testing to keep pace with the rapid rate of gene discovery resulting from the Human Genome Project. The Helix project began in 1992 at the University of Washington and Children's Hospital and Regional Medical Center. It has evolved from a single user stand alone relational database to a fully Web enabled database queried and maintained via the web and linked to other web accessible genomic databases. As of February, 1998 it lists more than 500 diseases and 290 laboratories, with over 5,200 registered users making approximately 250 queries/day (90% via the Internet). We describe the iterative design, implementation, population and assessment of the database over a six year period.

Database Management Systems↗

Amniotic fluid tumor necrosis factor-alpha and the risk of respiratory distress syndrome among preterm infants.

OBJECTIVE: We examined the effect of exposure to amniotic fluid infection and cytokines on the pulmonary outcome of preterm infants. STUDY DESIGN: A cohort of 136 preterm infants born to women in preterm labor had amniotic fluid cultures and tumor necrosis factor-alpha assays performed. Amniotic fluid was collected by transabdominal amniocentesis. Outcome measures included respiratory distress syndrome and length of oxygen and ventilator support. Logistic regression and Cox proportional hazards regression adjusted for birth weight and other confounders. RESULTS: Respiratory distress syndrome developed in 67 (49%) of 136 infants. Elevated amniotic fluid tumor necrosis factor-alpha levels and amniotic fluid infection were significantly associated with respiratory distress syndrome. This association persisted after adjustment for birth weight. Infants exposed to tumor necrosis factor-alpha remained on supplemental oxygen and assisted ventilation longer and had longer hospital stays compared with nonexposed infants. CONCLUSION: Prenatal exposure to tumor necrosis factor-alpha may be a risk factor for respiratory distress syndrome and its complications.

Amniocentesis↗

Shunt and ventilation-perfusion distribution during partial liquid ventilation in healthy piglets.

Replacing gas in the lung with perfluorocarbon fluids (PFC) and periodically ventilating with a gas [partial liquid ventilation (PLV)] has been shown to improve oxygenation in models of respiratory distress syndrome. We hypothesized that the addition of PFC to healthy lungs would result in shunt, diffusion impairment, and increased ventilation-perfusion (VA/Q) heterogeneity. Previously, Mates et al. showed that O2 shunt and arterial-alveolar CO2 difference increased linearly with dose in piglets given graded intratracheal doses of PFC (10, 20, and 30 ml/kg followed by mechanical ventilation with 100% O2) (E.A. Mates, J. C. Jackson, J. Hildebrandt, W. E. Truog, T. A. Standaert, and M. P. Hlastala. In: Oxygen Transport to Tissue XVI, 1994, p. 427-435). Here we report VA/Q distribution in the same animals, showing a 50% increase in VA/Q heterogeneity during PLV independent of PFC dose. Ventilation heterogeneity was the major factor in this increase, and there was no significant change in dead space ventilation. We also report on five animals given a single 20 ml/kg dose of PFC and followed for 3 h. They showed an increase in shunt during PLV but no change in arterial-alveolar CO2 difference.

Animals↗