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Integration of data derived from biological variation into the quality management system.

BACKGROUND: [corrected] Data on within- and between-subject biological variation are available for around 250 analytes commonly used in medical laboratories. METHODS: Integration of this data into the quality system occurs at all three levels of laboratory activity: (a) Preanalytic process: biological variation provides the basis for selecting the most appropriate specimen for analysis, for defining sample stability and for deciding suitable timing between samplings; (b) analytic process: biological variation-derived goals are fundamental for designing internal quality control procedures, and for evaluating laboratory performance; and (c) postanalytic process: delta checks based on within-subject biological variation values are used for validating results and for interpreting serial results from a patient. CONCLUSION: The biological variation is a pillar for managing quality in laboratory medicine.

Blood Chemical Analysis↗

Design of a description language for generating wrapper to collect biological data.

The biological data are scattered in various areas with various formats and they are changing continuously. Therefore, data integration becomes an important issue to provide researcher a dynamic access of data. In the data integration process, the method of extracting heterogeneous data dynamically from the data source is an essential part. Data extraction method using wrapper can provide flexibility and extensibility to an integration system.

Computational Biology↗

Cytophotometric DNA determinations and autoradiographic studies in salivary gland nuclei from larvae with different karyotypes in Drosophila melanogaster.

Cytophotometric DNA determinations in Feulgen stained mitotic diploid chromosome sets of neuroblasts from larvae of Drosophila melanogaster stocks, which possess different karyotypes, show significant differences between the 4C values, caused by an additional or deficient X- and Y-chromosome depending on the karyotype. The ranges of polytenic DNA size classes are theoretically expected to be doublings of the corresponding 4C mean value of each karyotype. The extinction integral data of nuclei with completely duplicated 4C quantities exclusively fall into the range of the expected size classes. Not all data falling into the range of a size class necessarily originate from duplicated nuclei, because the limits of the DNA size classes cannot be determined by measurements, but must be estimated from the confidence limits of the corresponding 4C mean value. The validity of the mitotic 4C values of the karyotypes X/X and X/Y is tested using data from non-labeled interphase nuclei, where extinction integral data accumulate in two groups. The larger values (= G2-nuclei) confirm the 4C values of mitotic chromosome sets, and the lower values (= G1-nuclei) are just half of these. Extinction integrals from individual, 3H-thymidine non-incorporating polytene salivary gland nuclei accumulate in distinct, non-overlapping groups which are always complete doublings of the preceding smaller group. In each karyotype, the most frequent data of each group are in accord with the 4C doublings. The data from labeled nuclei alternate with those from unlabeled nuclei. The measured DNA values of individual polytene nuclei that did not incorporate any 3H-thymidine, demonstrate that all chromosomal DNA replicates completely during polytenization of the chromosomes in the larval salivary gland nuclei of Drosophila melanogaster. Specifically, this would mean that the heterochromatic Y-chromosome replicates as well as the partially heterochromatic X-chromosome along with the autosomes. There is no indication of underreplicating heterochromatin.

Animals↗

Effect of uncertainty and diagnosticity on classification of multidimensional data with integral and separable displays of system status.

Integrative, objectlike displays have been advocated for presenting multidimensional system data. In this research two experiments assess the effect of uncertainty on the processing of integral and separable displays. In each experiment 30 subjects were trained to classify instances of system state into one of four state categories using a configural display, a bar graph display, or a digital display. In Experiment 1 the range of instances from the state categories was uniform; in Experiment 2 the distribution was biased toward those instances of highly uncertain state category membership. After training, subjects received extended practice classifying system data. In both experiments uncertainty was found to have the greatest effect on classification performance. In Experiment 1 the bar graph display was consistently superior; the configural display was superior to the digital display only under conditions of low uncertainty. In Experiment 2 the superiority of the bar graph display diminished, producing results equivalent to those of the digital display, with the configural display producing the worst performance. The effect of uncertainty on classification performance is discussed, with specific attention paid to the apparent configural and separable properties of the bar graph display.

Adolescent↗

A fix for data overload. CareGroup, Boston.

PROBLEM: Merger of seven hospitals into one network made existing information systems inadequate to track and control financial information. SOLUTION: Creation of a merged data movement and data integration solution to manage large files and complex, varied transactions. RESULTS: Data loading time significantly reduced, information updating more timely, data integration greatly enhanced. KEYS TO SUCCESS: Comparison testing of data-management products and on-site evaluation for applicability to specific needs.

Boston↗

Integration of genomic data in Electronic Health Records--opportunities and dilemmas.

OBJECTIVES: In this paper we give an overview about the challenge the postgenomic era poses on biomedical informaticists. The occurrence of new (genomic) data types necessitates new data models, new viewing metaphors and methods to deal with the disclosure of genomic data. We discuss integration issues when inferring phenotype and genotype data. Another challenge is to find the right phenotype to genotype data in order to get appropriate case numbers for sound clinical genotype-phenotype inference studies. METHODS: Genomic data could be integrated in an Electronic Health Record (EHR) in several ways. We describe patient-centered and pointer-based integration strategies and the corresponding data types and data models. The inference mechanisms for the interpretation of row data contain different agents. We describe vertical, horizontal and temporal agents. RESULTS: We have to deal with several new data types, not being standardized for EHR integration. Genomic data tends to be more structured than phenotype data. Beyond the development of new data models, vertical, horizontal and temporal agents have to be developed in order to link genotype and phenotype. As the genomic EHR will contain very sensitive data, confidentiality and privacy concerns have to be addressed. CONCLUSIONS: Given the necessity to capture both environment and genomic state of a patient and their interaction, clinical information systems have to be redesigned. While genotyping seems to be automatable easily, this is not the case for clinical information. More integration work on terminologies and ontologies has to be done.

Computational Biology↗

Integration of different data bodies for humanitarian decision support: an example from mine action.

Geographic information systems (GIS) are increasingly used for integrating data from different sources and substantive areas, including in humanitarian action. The challenges of integration are particularly well illustrated by humanitarian mine action. The informational requirements of mine action are expensive, with socio-economic impact surveys costing over US$1.5 million per country, and are feeding a continuous debate on the merits of considering more factors or 'keeping it simple'. National census offices could, in theory, contribute relevant data, but in practice surveys have rarely overcome institutional obstacles to external data acquisition. A positive exception occurred in Lebanon, where the landmine impact survey had access to agricultural census data. The challenges, costs and benefits of this data integration exercise are analysed in a detailed case study. The benefits are considerable, but so are the costs, particularly the hidden ones. The Lebanon experience prompts some wider reflections. In the humanitarian community, data integration has been fostered not only by the diffusion of GIS technology, but also by institutional changes such as the creation of UN-led Humanitarian Information Centres. There is a question whether the analytic capacity is in step with aggressive data acquisition. Humanitarian action may yet have to build the kind of strong analytic tradition that public health and poverty alleviation have accomplished.

Agriculture↗

The use of physiologically based models to integrate diverse data sets and reduce uncertainty in the prediction of perchlorate and iodide kinetics across life stages and species.

The effects of perchlorate on the incorporation of iodide into thyroid hormones have been studied for more than 40 years in many species and under varying exposure conditions. Nevertheless, the database for this drinking water contaminant is still incomplete, particularly with regard to human developmental risk. A method for integrating the available data and forming meaningful conclusions for risk assessment is needed. To this end, an initial suite of physiologically based pharmacokinetic (PBPK) models has been developed, which incorporates physiological data for the relevant species and life stages and kinetic data for perchlorate and iodide, as well as the interaction between the two anions. The validated models successfully describe perchlorate-induced inhibition of thyroid iodide uptake and perchlorate and iodide kinetics in the male, pregnant, lactating, fetal, and neonatal rats and the adult humans. The relationships of model-predicted internal dose metrics and kinetic parameters allow a direct comparison of internal dose metrics across life stages in rats and humans. By incorporating all the available data, these models provide a framework for species and life stage extrapolation where the lack of specific data sets would otherwise limit predictive capability. This paper demonstrates two approaches for calculating life stage-specific equivalent doses in a risk assessment for perchlorate: the direct combination of validated model predictions, and the development of preliminary PBPK models for the human-sensitive populations based on the relationship of the parameters in the validated rat and human models. Either approach can be used to perform the needed dosimetry. However, the second approach provides the advantage of a preliminary human life stage-specific PBPK model that can be used for identification of key data gaps and estimation of uncertainty.

Age Factors↗

Development of an integrated genome informatics, data management and workflow infrastructure: a toolbox for the study of complex disease genetics.

The genetic dissection of complex disease remains a significant challenge. Sample-tracking and the recording, processing and storage of high-throughput laboratory data with public domain data, require integration of databases, genome informatics and genetic analyses in an easily updated and scaleable format. To find genes involved in multifactorial diseases such as type 1 diabetes (T1D), chromosome regions are defined based on functional candidate gene content, linkage information from humans and animal model mapping information. For each region, genomic information is extracted from Ensembl, converted and loaded into ACeDB for manual gene annotation. Homology information is examined using ACeDB tools and the gene structure verified. Manually curated genes are extracted from ACeDB and read into the feature database, which holds relevant local genomic feature data and an audit trail of laboratory investigations. Public domain information, manually curated genes, polymorphisms, primers, linkage and association analyses, with links to our genotyping database, are shown in Gbrowse. This system scales to include genetic, statistical, quality control (QC) and biological data such as expression analyses of RNA or protein, all linked from a genomics integrative display. Our system is applicable to any genetic study of complex disease, of either large or small scale.

Animals↗

A Bayesian system integrating expression data with sequence patterns for localizing proteins: comprehensive application to the yeast genome.

We develop a probabilistic system for predicting the subcellular localization of proteins and estimating the relative population of the various compartments in yeast. Our system employs a Bayesian approach, updating a protein's probability of being in a compartment, based on a diverse range of 30 features. These range from specific motifs (e.g. signal sequences or the HDEL motif) to overall properties of a sequence (e.g. surface composition or isoelectric point) to whole-genome data (e.g. absolute mRNA expression levels or their fluctuations). The strength of our approach is the easy integration of many features, particularly the whole-genome expression data. We construct a training and testing set of approximately 1300 yeast proteins with an experimentally known localization from merging, filtering, and standardizing the annotation in the MIPS, Swiss-Prot and YPD databases, and we achieve 75 % accuracy on individual protein predictions using this dataset. Moreover, we are able to estimate the relative protein population of the various compartments without requiring a definite localization for every protein. This approach, which is based on an analogy to formalism in quantum mechanics, gives better accuracy in determining relative compartment populations than that obtained by simply tallying the localization predictions for individual proteins (on the yeast proteins with known localization, 92% versus 74%). Our training and testing also highlights which of the 30 features are informative and which are redundant (19 being particularly useful). After developing our system, we apply it to the 4700 yeast proteins with currently unknown localization and estimate the relative population of the various compartments in the entire yeast genome. An unbiased prior is essential to this extrapolated estimate; for this, we use the MIPS localization catalogue, and adapt recent results on the localization of yeast proteins obtained by Snyder and colleagues using a minitransposon system. Our final localizations for all approximately 6000 proteins in the yeast genome are available over the web at: http://bioinfo.mbb.yale. edu/genome/localize.

Amino Acid Motifs↗

Internet-enabled high-resolution brain mapping and virtual microscopy.

Virtual microscopy involves the conversion of histological sections mounted on glass microscope slides to high-resolution digital images. Virtual microscopy offers several advantages over traditional microscopy, including remote viewing and data sharing, annotation, and various forms of data mining. We describe a method utilizing virtual microscopy for generation of internet-enabled, high-resolution brain maps and atlases. Virtual microscopy-based digital brain atlases have resolutions approaching 100,000 dpi, which exceeds by three or more orders of magnitude resolutions obtainable in conventional print atlases, MRI, and flat-bed scanning. Virtual microscopy-based digital brain atlases are superior to conventional print atlases in five respects: (1) resolution, (2) annotation, (3) interaction, (4) data integration, and (5) data mining. Implementation of virtual microscopy-based digital brain atlases is located at BrainMaps.org, which is based on more than 10 million megapixels (35 terabytes) of scanned images of serial sections of primate and non-primate brains with a resolution of 0.46 microm/pixel (55,000 dpi). The method can be replicated by labs seeking to increase accessibility and sharing of neuroanatomical data. Online tools offer the possibility of visualizing and exploring completely digitized sections of brains at a sub-neuronal level and can facilitate large-scale connectional tracing, histochemical, and stereological analyses.

Animals↗

Pelvic floor exercises during and after pregnancy: a systematic review of their role in preventing pelvic floor dysfunction.

OBJECTIVE: To review the literature on the origin, anatomical rationale, techniques, and evidence-based effectiveness of peripartum pelvic floor exercises (PFEs) in the prevention of pelvic floor problems including urinary and anal incontinence, and prolapse. DATA SOURCES: Literature was reviewed for background information. MEDLINE, EMBASE, CINAHL, and proceedings of scientific meetings were searched for evidence-based data. A comprehensive literature search was performed to find all studies that involved the use of antepartum and/or postpartum PFEs. For the MEDLINE (1966 to 2002) and CINAHL (1980 to 2002) searches, the following key words were used: urinary incontinence (prevention and control, rehabilitation, therapy), fecal incontinence, exercise or exercise therapy, Kegel, muscle contraction, muscle tonus, muscle development, pelvic floor, pregnancy, puerperium, puerperal disorders. For the EMBASE (1980 to 2002) search, the following key words were used: micturition disorder (prevention, rehab, disease management, therapy), fecal incontinence, labour complication, pregnancy disorder, puerperal disorder, antepartum care, pregnancy, kinesiotherapy, exercise, pelvic floor, bladder. A manual search was performed of available abstracts presented at the annual scientific meetings of the International Continence Society (1997, 1999 to 2002), American Urogynecologic Association (1997 to 1998, 2000 to 2002), and International Urogynecological Association (1997, 1999 to 2002). Twelve studies evaluating the role of antepartum PFE were found, of which 3 randomized controlled trials (RCTs) comparing PFEs for the prevention of urinary incontinence to controls were included. Twelve studies evaluating postpartum PFEs for prevention of urinary incontinence were reviewed, of which 4 RCTs were included. Five studies evaluating postpartum PFEs for the prevention of anal incontinence were reviewed, of which 4 RCTs were included. Participants in the studies were primiparous women. DATA TABULATION AND INTEGRATION: Data were extracted using a standardized collection form. Quality of the data was evaluated using the Jadad scale. Where possible, a meta-analysis was conducted using a random effect model. Heterogeneity between trials was assessed and sensitivity analyses were performed. RESULTS: Antepartum PFEs, when used with biofeedback and taught by trained health care personnel, using a conservative model, does not result in significant short-term (3 months) decrease in postpartum urinary incontinence, or pelvic floor strength. Postpartum PFEs, when performed with a vaginal device providing resistance or feedback, appear to decrease postpartum urinary incontinence and to increase strength. Reminder and motivational systems to perform "Kegel" exercises are ineffective in preventing postpartum urinary incontinence. Postpartum PFEs do not consistently reduce the incidence of anal incontinence. CONCLUSION: Postpartum PFEs appear to be effective in decreasing postpartum urinary incontinence. Data regarding the effect of PFEs on prevention of anal incontinence are lacking, and also on its prevention of prolapse.

Evidence-Based Medicine↗

A Web-based, secure, light weight clinical multimedia data capture and display system.

Computer-based patient records are traditionally composed of textual data. Integration of multimedia data has been historically slow. Multimedia data such as image, audio, and video have been traditionally more difficult to handle. An implementation of a clinical system for multimedia data is discussed. The system implementation uses Java, Secure Socket Layer (SSL), and Oracle 8i. The system is on top of the Internet so it is architectural independent, cross-platform, cross-vendor, and secure. Design and implementations issues are discussed.

Computer Security↗

[Colon cancer and nutritional genetics: modifier genes].

About 5% of colon cancer cases correspond to classic hereditary monogenic mendelian transmission involving at least 8 major genes of predisposition to this tumor. Genes with more moderate effects, in association with other genes can contribute to the occurrence of sporadic polygenic forms. These genes confer susceptibility to environmental factors and can play the role of aggravating or protective modifier genes in the different hereditary forms. Foods can interact with these genes and modulate their expression. Moreover sequence variations (polymorphisms) in these genes may also be responsible for slower or more rapid metabolism of nutrients leading to toxic or carcinogenic compounds. If some foods, or "pharmafoods" can have beneficial effects in some individuals with a particular subtype of the disease, others can be inefficient or even detrimental in patients with the same disease but with a different genetic origin or if the genetic background is different. Moreover tumorigenic processes are diverse. Tumor progression depends on genetic and environmental factors different from tumor initiation and on the site of the tumor along the colon tract. Interactions with the gut flora, the lymphoid system and specific features of growth of the colon mucosa are also important parameters. Today with a formidable genetic knowledge arising from the genome project, new epidemiological data integrating the genetic data for multiple markers and a better knowledge of the tumorigenic processes involved, a new discipline is emerging. "Nutrigenetics" which is the study of hereditary basis of individual variations in response to foods opens for the oncoming decade the era of a personalised predictive medecine based on a nutrition adapted to the genetic make up of each of us.

Cocarcinogenesis↗

YMD: a microarray database for large-scale gene expression analysis.

The use of microarray technology to perform parallel analysis of the expression pattern of a large number of genes in a single experiment has created a new frontier of medical research. The vast amount of gene expression data generated from multiple microarray experiments requires a robust database system that allows efficient data storage, retrieval, secure access, data dissemination, and integrated data analyses. To address the growing needs of microarray researchers at Yale and their collaborators, we have built the Yale Microarray Database (YMD). YMD is Web-accessible with the following features: (i) a Web program that tracks DNA samples between source plates and arrays, (ii) the capability of finding common genes/clones across different array platforms, (iii) an image file server, (iv) laboratory-based user management and access privileges, (v) project management, (vi) template data entry, (vii) linking gene expression data to annotation databases for functional analysis. YMD is currently being used on a pilot basis by several laboratories for different organisms and array platforms.

Databases, Nucleic Acid↗

Integrating OASIS data collection into a comprehensive assessment.

OASIS should not be used as a survey tool; rather, it should be integrated into a comprehensive assessment. It is almost never appropriate to simply read OASIS questions verbatim to patients and expect them to name the letter of the response. This article provides strategies for collecting OASIS data as part of a routine patient comprehensive assessment.

Data Collection↗

Toward large-scale mass spectrometry-based omics for clinical applications.

INTRODUCTION: As healthcare advances toward personalized medicine, mass spectrometry-based research is advancing our understanding of cellular biology and disease states, and translating these findings into clinical applications. This review highlights recent advances in methodology and technology that demonstrate the capabilities of mass spectrometry-based proteomics, lipidomics, and metabolomics in clinical practice. AREAS COVERED: The ability to directly analyze functional molecules with mass spectrometry uncovers crucial clinical information. Each data modality (proteins, lipids, and metabolites) provides essential insight into healthy and disease states. As technology advances, integrating data from different modalities unlocks new possibilities for clinical research. To gain the most from this multi-omic data, unsupervised integration methods can provide detailed insights into complex biological processes. As the field applies this knowledge, healthcare could experience significant leaps in the near future. This review examines recent advancements in mass spectrometry-based proteomics, lipidomics, and metabolomics, focusing on how improvements in sample preparation, automation, and multi-omics data integration are making large-scale clinical studies more accessible. EXPERT OPINION: Recent technical and methodological advancements in mass spectrometry analysis have propelled healthcare toward a tipping point, shifting from traditional RNA- and DNA-based research to downstream analysis of protein, lipid, and metabolite effectors.

Humans↗