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PubMed1992

A method for developing and maintaining a powerful but inexpensive computer data base of clinical information about emergency department patients.

We describe a method of creating and maintaining a computer data base containing demographic, diagnostic, procedural, and laboratory data on all emergency department patients. The data base is inexpensive because it avoids redundant data entry; instead, it relies on data already entered into the hospital computers. It is unobtrusive because the ED providers do not have to complete any extra paperwork; data captured on other hospital computers are transferred to the ED data base, making the ED computer a data "parasite." It is powerful because data can be extracted in arbitrarily complex ways using common relational data base software. The data base facilitates administrative, quality improvement, and research tasks for ED managers and researchers. By using standard diagnostic and procedural coding schemes, comparison of patient populations from different EDs can be accomplished. The technologic and financial requirements of this type of data base are within the reach of most EDs.

Computer Communication Networks↗

PubMed2004

Conforming to HIPAA regulations and compilation of research data.

PURPOSE: A set of deidentified patient data compliant with the Health Information Portability and Accountability Act (HIPAA) was compiled, the data lost as a function of unique data elements (UDEs) were measured, and the deidentified data were tested for potential for reidentification. METHODS: After approval by the institutional review board of an integrated health system, a limited-data set was created by querying the health system's pharmacy, administrative, and financial files for patients discharged between January 1 and December 31, 2000. Using the HIPAA "safe-harbor" method, this limited-data set was converted into a deidentified-data table for future statistical analysis, and UDEs in both data sets were identified and quantified. Unique combinations of commonly available data were also identified. RESULTS: The limited-data set, representing 4,738 patient discharges, contained 810,456 UDEs in 322,657 records organized into four data tables (demographics, diagnoses, medication orders, and laboratory test results). The deidentified-data table, representing 4,722 discharges, contained 562,171 UDEs in 128 data-type columns in a single data table. About 31% of the data volume was lost. Much of the information lost was of the type that is of special interest to researchers (e.g., time between episodes of care, ages of >89 years). CONCLUSION: A study suggested that deidentified patient data with a reasonable degree of protection against reidentification were less complete than may be necessary for good research.

Guideline Adherence↗

PubMed2006

Integrating structured biological data by Kernel Maximum Mean Discrepancy.

MOTIVATION: Many problems in data integration in bioinformatics can be posed as one common question: Are two sets of observations generated by the same distribution? We propose a kernel-based statistical test for this problem, based on the fact that two distributions are different if and only if there exists at least one function having different expectation on the two distributions. Consequently we use the maximum discrepancy between function means as the basis of a test statistic. The Maximum Mean Discrepancy (MMD) can take advantage of the kernel trick, which allows us to apply it not only to vectors, but strings, sequences, graphs, and other common structured data types arising in molecular biology. RESULTS: We study the practical feasibility of an MMD-based test on three central data integration tasks: Testing cross-platform comparability of microarray data, cancer diagnosis, and data-content based schema matching for two different protein function classification schemas. In all of these experiments, including high-dimensional ones, MMD is very accurate in finding samples that were generated from the same distribution, and outperforms its best competitors. CONCLUSIONS: We have defined a novel statistical test of whether two samples are from the same distribution, compatible with both multivariate and structured data, that is fast, easy to implement, and works well, as confirmed by our experiments. AVAILABILITY: http://www.dbs.ifi.lmu.de/~borgward/MMD.

Algorithms↗

PubMed2005

An expectation-maximization-likelihood-ratio test for handling missing data: application in experimental crosses.

The mapping of quantitative trait loci (QTL) is an important research question in animal and human studies. Missing data are common in such study settings, and ignoring such missing data may result in biased estimates of the genotypic effect and thus may eventually lead to errant results and incorrect inferences. In this article, we developed an expectation-maximization (EM)-likelihood-ratio test (LRT) in QTL mapping. Simulation studies based on two different types of phylogenetic models revealed that the EM-LRT, a statistical technique that uses EM-based parameter estimates in the presence of missing data, offers a greater statistical power compared with the ordinary analysis-of-variance (ANOVA)-based test, which discards incomplete data. We applied both the EM-LRT and the ANOVA-based test in a real data set collected from F2 intercross studies of inbred mouse strains. It was found that the EM-LRT makes an optimal use of the observed data and its advantages over the ANOVA F-test are more pronounced when more missing data are present. The EM-LRT method may have important implications in QTL mapping in experimental crosses.

Algorithms↗

PubMed1998

The role of zinc lozenges in treatment of the common cold.

OBJECTIVE: To summarize and critique the medical literature on the use of zinc lozenges for treatment of the common cold. DATA SOURCES: MEDLINE searches (January 1966-June 1997) identified human clinical trials on the use of zinc lozenges for the treatment of the common cold. Bibliographies were also reviewed for relevant articles. STUDY SELECTION: Double-blind, placebo-controlled trials of zinc lozenges in adults for the treatment of the common cold, with the clinical end points of reduction in duration and/or severity of cold symptoms. DATA EXTRACTION: All double-blind placebo-controlled, human clinical trials on the use of zinc lozenges for the treatment of the common cold were included. DATA SYNTHESIS: The use of zinc lozenges in the treatment of the common cold has been suggested to reduce the duration and severity of cold symptoms. Of eight double-blind, placebo-controlled trials, four found zinc lozenges to be effective, while the other four reported no difference between zinc and placebo therapy. Potential reasons for the discrepancy between the results of these trials include inadequate placebo control, formulation of the lozenge, and the dose of zinc used. Common adverse effects include unpleasant taste, mouth irritation, and nausea. CONCLUSIONS: Treatment of the common cold with zinc gluconate lozenges, using adequate doses of elemental zinc, may be effective in reducing duration and severity of cold symptoms. The benefit appears to be maximal if the lozenges are started immediately after the onset of symptoms. The formulation of the lozenges also appears to be important because the addition of citric acid or tartaric acid may reduce efficacy due to chelation of zinc ion. Although zinc gluconate lozenges have dominated clinical trials thus far, further studies are needed to demonstrate the efficacy of zinc acetate lozenges and to determine whether their adverse effect profile is more favorable to that of zinc gluconate lozenges. Patients should play an important role in the decision-making process and must decide whether the benefit gained from treatment with zinc lozenges outweighs the potential adverse effects.

Common Cold↗

PubMed1978

Excretion of common neutral steroids in healthy subjects as estimated by multi-column chromatography.

Excretion data for common neutral urinary steroids from a total of 330 healthy subjects from different parts of the world and of different sex and age are given. The estimations, which have been performed by multi-column liquid chromatography, include 24 h excretion values for both common 17-oxosteroids and the common metabolites of cortisol, including the cortolones and the cortols. Comparisons are made with values from the world literature and with isotope experiments.

17-Ketosteroids↗

PubMed2000

Electron microscopy and subunit-subunit interaction studies reveal a first architecture of COP9 signalosome.

The COP9 signalosome is involved in signal transduction, whereas the 26 S proteasome lid is a regulatory subcomplex of the 26 S proteasome responsible for degradation of ubiquitinated proteins. COP9 signalosome and lid possess significant sequence homologies among their eight core subunits and are likely derived from a common ancestor. Surprisingly, from our two-dimensional electron microscopy data, a common architectural plan for the two complexes could not be deduced. None-the-less, the two particles have structural features in common. Both COP9 signalosome and lid lack any symmetry in subunit arrangement and exhibit a central groove, possibly qualified for scaffolding functions.Filter-binding assays with recombinant COP9 signalosome components revealed a multitude of subunit-subunit interactions, supporting the asymmetrical appearance of the complex in electron microscopy. On the basis of two-dimensional images and subunit interaction studies, a first architectural model of COP9 signalosome was created. The fact that four distinct classes of particle views were identified and that only 50 % of the selected particles could be classified indicates a high degree of heterogeneity in electron microscopic images. Different orientations with respect to the viewing axis and conformational variety, presumably due to different grades of phosphorylation, are possible reasons for the heterogeneous appearance of the complex. Our biochemical data show that recombinant COP9 signalosome subunits 2 and 7 are phosphorylated by the associated kinase activity. The modification of COP9 signalosome subunit 2 might be essential for c-Jun phosphorylation. Dephosphorylation does not inactivate the associated kinase activity. Although substrate phosphorylation by COP9 signalosome is significantly decreased by lambda protein phosphatase treatment, "autophosphorylation" is increased.

COP9 Signalosome Complex↗

PubMed2025

Permutation tests to assess sex differences in omics data.

It is common to sex-stratify analyses of omics data and to report effects as 'sex-specific' when they are significant in only one sex. However, when analysing hundreds or thousands of molecules, this approach will yield many spurious 'sex-specific' effects if not supported by significant interactions. I illustrate this problem using an RNA sequencing dataset showing almost no significant sex by treatment interactions, but where sex-stratified analyses yield hundreds of 'sex-specific' effects of treatment. These 'sex-specific' effects could be spurious or could be real but not show interactions due to low statistical power. To distinguish these possibilities, I describe permutation tests, which provide an intuitive way to determine if a pattern of observations differs from what would be expected due to chance. For this dataset, assigning sex at random often generates more 'sex-specific' effects than the real data, demonstrating that there is little evidence of sex differences. Next, I simulate an RNA sequencing dataset that includes genes modelled to have sex-specific effects of a condition. As expected, analysis of this simulated dataset yields both significant interactions and sex-specific effects in sex-stratified analyses. While stratified analyses detect a higher number of sex-specific effects than the analysis of interactions, they erroneously identify genes not modelled to show sex-specific effects more often than interactions. A permutation test confirms that the number of sex-specific effects observed in the simulated dataset is greater than expected due to chance. Permutation tests can be applied to omics studies of sex differences, simultaneously providing (i) a clear and simple demonstration of the problems of sex-stratified analyses, and (ii) additional evidence of sex-specific effects where these are present. R code is provided for permutations, simulations, and plots to visualize potential sex-specific effects, which can be adapted to other types of data.

Female↗

PubMed1988

CSE (common standards for quantitative electrocardiography) data testing in Japan.

The authors comment on the present status of computerized electro-cardiogram (ECG) works in Japan and demonstrate the preliminary tentative results of CSE (common standards for quantitative electrocardiography) data analysis using the Nagoya program. The more detailed results of the performance of several programs in CSE data analysis are discussed by Dr. Willems.

Diagnosis, Computer-Assisted↗

PubMed2006

Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis.

BACKGROUND: Common fragile sites (cfs) are specific regions in the human genome that are particularly prone to genomic instability under conditions of replicative stress. Several investigations support the view that common fragile sites play a role in carcinogenesis. We discuss a genome-wide approach based on graph theory and Gene Ontology vocabulary for the functional characterization of common fragile sites and for the identification of genes that contribute to tumour cell biology. RESULTS: Common fragile sites were assembled in a network based on a simple measure of correlation among common fragile site patterns of expression. By applying robust measurements to capture in quantitative terms the non triviality of the network, we identified several topological features clearly indicating departure from the Erdos-Renyi random graph model. The most important outcome was the presence of an unexpected large connected component far below the percolation threshold. Most of the best characterized common fragile sites belonged to this connected component. By filtering this connected component with Gene Ontology, statistically significant shared functional features were detected. Common fragile sites were found to be enriched for genes associated to the immune response and to mechanisms involved in tumour progression such as extracellular space remodeling and angiogenesis. Moreover we showed how the internal organization of the graph in communities and even in very simple subgraphs can be a starting point for the identification of new factors of instability at common fragile sites. CONCLUSION: We developed a computational method addressing the fundamental issue of studying the functional content of common fragile sites. Our analysis integrated two different approaches. First, data on common fragile site expression were analyzed in a complex networks framework. Second, outcomes of the network statistical description served as sources for the functional annotation of genes at common fragile sites by means of the Gene Ontology vocabulary. Our results support the hypothesis that fragile sites serve a function; we propose that fragility is linked to a coordinated regulation of fragile genes expression.

Cells, Cultured↗

PubMed2006

Trauma registry data validation: Essential for quality trauma care.

BACKGROUND: The main function of a trauma registry is to assess quality assurance and performance improvement (QA/PI) in an individual institution. Nonvalidated registry data may produce unreliable reports and QA/PI information. This study examines the types of data entry errors in a trauma registry database; the effect of errors on time variable estimates, case ascertainment and statistical measurement; dynamics of error occurrence; and data validation (DV) scheme for a trauma registry. METHODS: Query and cross-tabulation techniques were used to expose a variety of data entry errors. Conceptual aspect for each type of error in DV, especially with respect to QA/PI, is given. RESULTS: Findings of different errors are provided: out-of-range time values; false positive and false negative errors; errors of commission and omission; duplication errors; errors in demographics; and errors because of inconsistent and incongruent coding. Error rates were less than 3% in commonly occurring data, such as scene time, demographics, hospital discharge and transportation, and greater in less commonly occurring but important data, such as thoracic aorta injury (9.5%) and audit filter for admit Glasgow Coma Scale in emergency department (55.6%). Dynamics of error occurrence that can prevent or minimize errors is described. The main features of a data validation scheme are displayed. CONCLUSIONS: Errors in a trauma registry database cause invalid frequencies, rates, time estimates and statistical measures and affect QA/PI in trauma care. Every functioning trauma registry should develop an on-going program for DV.

Bias↗

PubMed2000

The application of multilevel, multivariate modelling to orthodontic research data.

OBJECTIVE: To demonstrate the use of multilevel multivariate modelling in the evaluation of multiple outcome dental data. BASIC RESEARCH DESIGN: Multiple outcome dental research data are used to illustrate the problems of analysing such complex information structures i.e. several outcomes clustered within subjects. Appropriate and statistically efficient methods of data analysis are proposed and illustrated step-by-step. The data structure is analysed using multilevel multivariate regression techniques and this process is discussed in comparison to conventional single-level multiple regression. PARTICIPANTS: Questionnaire data were obtained from an orthognathic study of 84 subjects seeking treatment and 106 'non-treatment' controls (full details of which are reported elsewhere). RESULTS: Multivariate multiple regression analysis demonstrated a number of advantages over separate single-level multiple regression approaches, including a gain in statistical efficiency and greater insight into: a) the role of (significant) explanatory variables and b) outcome variable interactions. Multilevel multivariate analysis reduced the risk of both Tipe I and Type II statistical errors. CONCLUSIONS: The study demonstrates the benefit of multilevel multivariate modelling over conventional single-level techniques for statistical analysis of multiple outcome data. As a result of ongoing technical developments in the power, speed and memory of modern PCs, multilevel multivariate regression can now be undertaken with relative ease. Consequently, researchers are better equipped to analyse such complex data structures, particularly within dentistry where multivariate data are common.

Data Interpretation, Statistical↗

PubMed2005

The tissue micro-array data exchange specification: a web based experience browsing imported data.

BACKGROUND: The AIDS and Cancer Specimen Resource (ACSR) is an HIV/AIDS tissue bank consortium sponsored by the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis (DCTD). The ACSR offers to approved researchers HIV infected biologic samples and uninfected control tissues including tissue cores in micro-arrays (TMA) accompanied by de-identified clinical data. Researchers interested in the type and quality of TMA tissue cores and the associated clinical data need an efficient method for viewing available TMA materials. Because each of the tissue samples within a TMA has separate data including a core tissue digital image and clinical data, an organized, standard approach to producing, navigating and publishing such data is necessary. The Association for Pathology Informatics (API) extensible mark-up language (XML) TMA data exchange specification (TMA DES) proposed in April 2003 provides a common format for TMA data. Exporting TMA data into the proposed format offers an opportunity to implement the API TMA DES. Using our public BrowseTMA tool, we created a web site that organizes and cross references TMA lists, digital "virtual slide" images, TMA DES export data, linked legends and clinical details for researchers. Microsoft Excel and Microsoft Word are used to convert tabular clinical data and produce an XML file in the TMA DES format. The BrowseTMA tool contains Extensible Stylesheet Language Transformation (XSLT) scripts that convert XML data into Hyper-Text Mark-up Language (HTML) web pages with hyperlinks automatically added to allow rapid navigation. RESULTS: Block lists, virtual slide images, legends, clinical details and exports have been placed on the ACSR web site for 14 blocks with 1623 cores of 2.0, 1.0 and 0.6 mm sizes. Our virtual microscope can be used to view and annotate these TMA images. Researchers can readily navigate from TMA block lists to TMA legends and to clinical details for a selected tissue core. Exports for 11 blocks with 3812 cores from three other institutions were processed with the BrowseTMA tool. Fifty common data elements (CDE) from the TMA DES were used and 42 more created for site-specific data. Researchers can download TMA clinical data in the TMA DES format. CONCLUSION: Virtual TMAs with clinical data can be viewed on the Internet by interested researchers using the BrowseTMA tool. We have organized our approach to producing, sorting, navigating and publishing TMA information to facilitate such review. We have converted Excel TMA data into TMA DES XML, and imported it and TMA DES XML from another institution into BrowseTMA to produce web pages that allow us to browse through the merged data. We proposed enhancements to the TMA DES as a result of this experience. We implemented improvements to the API TMA DES as a result of using exported data from several institutions. A document type definition was written for the API TMA DES (that optionally includes proposed enhancements). Independent validators can be used to check exports against the DTD (with or without the proposed enhancements). Linking tissue core images to readily navigable clinical data greatly improves the value of the TMA.

AIDS-Related Complex↗

PubMed2000

Comparability of thermodynamic data--a metrological point of view.

In order to compare and to interpret chemical measurements, compliance with general rules of metrology is compulsory. Such rules are the more important the more the chemical measurements are applied under circumstances where material assets and goods or immaterial values like health may be affected. Metrology of chemical measurements attempts to define rules for achieving comparability and for guaranteeing quality of analytical data. Thermodynamic data are commonly derived from a set of analytical measurements. Comparability among thermodynamic data is an important issue especially for those data to be applied in politically sensitive issues of environmental prognosis, long-term safety assessment of nuclear waste repositories in deep geological formations and assessment of environmental impact of technical intervention in the geosphere. Taking the data evaluation step in the traceability chain of thermodynamic data as an example, the existing thermodynamic data is shown to be affected by deficiencies in comparability and quality that may severely limit its dependability in environmental prognosis. The need for a metrologically acceptable approach is demonstrated. Statistical concepts improving a reliable assignment of meaningful measurement uncertainty to a thermodynamic datum are presented. Unresolved issues, i.e. measurement uncertainty of a pH measurement, hampering the construction of a traceability chain are outlined.

Journal Article↗

PubMed2005

Handling outliers in brain tumour MRS data analysis through robust topographic mapping.

Uncertainty is inherent in medical decision making and poses a challenge for intelligent technologies. This paper focuses on magnetic resonance spectra (MRS) for discrimination of brain tumour types and grades. Modelling of this type of high-dimensional data is commonly affected by uncertainty caused by the presence of outliers. Multivariate data clustering and visualization of MRS data is proposed using the GTM framework with basis functions comprising Student t-distributions in order to minimize the negative impact on the model from outliers. The effectiveness of this model on the MRS data is demonstrated empirically.

Brain↗

PubMed2003

Static innominate asymmetry and leg length discrepancy in asymptomatic collegiate athletes.

The objectives of the study were to assess: (1) static innominate asymmetry in the sagittal plane, (2) leg length discrepancy (LLD), and (3) the relationship between static innominate rotation and LLD in asymptomatic collegiate athletes. The study was an observational study by design which took place in a University athletic training research laboratory. The participants were twenty-four male and 20 female asymptomatic intercollegiate athletes who volunteered to take part in the study. Static innominate asymmetry was assessed with a caliper/inclinometer tool and LLD was measured with a tape measure using standard clinical methods. Results showed that forty-two subjects (95%) demonstrated some degree of static innominate asymmetry. In 32 subjects (73%), the right innominate was more anteriorly rotated than the left. Nearly all subjects were determined to have unequal leg lengths with a majority, 30 subjects (68%), showing a slightly longer left leg. Weak correlations (r=0.33 - 0.44) were identified between static innominate asymmetry and LLD. In Conclusion static innominate asymmetry and LLD are common among asymptomatic collegiate athletes. This information provides clinicians with normative data of common clinical measures in a physically active population.

Adult↗

PubMed2006

Mouse Phenome Database (MPD).

The Mouse Phenome Database (MPD; http://www.jax.org/phenome) is a repository of phenotypic and genotypic data on commonly used and genetically diverse inbred strains of mice. Strain characteristics data are contributed by members of the scientific community. Electronic access to centralized strain data enables biomedical researchers to choose appropriate strains for many systems-based research applications, including physiological studies, drug and toxicology testing and modeling disease processes. MPD provides a community data repository and a platform for data analysis and in silico hypothesis testing. The laboratory mouse is a premier genetic model for understanding human biology and pathology; MPD facilitates research that uses the mouse to identify and determine the function of genes participating in normal and disease pathways.

Animals↗

PubMed2006

Transcriptomic response to differentiation induction.

BACKGROUND: Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes. METHODS: We applied a transcriptomics analysis tool to elucidate the underlying pathways of leukocyte maturation at the genomic level in an established cellular model of leukemia by examining time-course data in two subclones of U-937 cells. Leukemias such as Acute Promyelocytic Leukemia (APL) are characterized by a block in the hematopoietic stem cell maturation program at a point when expansion of clones which should be destined to mature into terminally-differentiated effector cells get locked into endless proliferation with few cells reaching maturation. Treatment with retinoic acid, depending on the precise genomic abnormality, often releases the responsible promyelocytes from this blockade but clinically can yield adverse sequellae in terms of potentially lethal side effects, referred to as retinoic acid syndrome. RESULTS: Briefly, the list of genes for temporal patterns of expression was pasted into the ABCC GRID Promoter TFSite Comparison Page website tool and the outputs for each pattern were examined for possible coordinated regulation by shared regelems (regulatory elements). We found it informative to use this novel web tool for identifying, on a genomic scale, genes regulated by drug treatment. CONCLUSION: Improvement is needed in understanding the nature of the mutations responsible for controlling the maturation process and how these genes regulate downstream effects if there is to be better targeting of chemical interventions. Expanded implementation of the techniques and results reported here may better direct future efforts to improve treatment for diseases not restricted to APL.

Cell Differentiation↗