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Determination of neurochemicals in biological fluids by using an automated high-performance liquid chromatographic system with a coulometric array detector.

The chromatographic separation of 33 neurochemicals was achieved by using a combined gradient of organic modifier, pH and counter-ion. A secondary separation of unresolved analytes was obtained by using electrochemical detection with a coulometric array of sixteen electrodes. The stability of the analytes was studied and data on analytical performance are reported in addition to a list of neurochemicals detected in a normal plasma sample.

Brain Chemistry↗

[Necessity for and construction of cytological data banks].

Analytical and quantitative cytology is based upon photometric and morphometric measurements of single cells in stained cytological specimens. It analyzes the features of single cells and cell populations with respect to their cytodiagnostic relevance. One way to do this is the establishment of learning sets of visually selected cells, and the intercomparison of unknown cells with these data sets. Difficulties arise with the visual classification of single cells from PAP-stained gynecological smears and the pooling into classes due to the considerable photometric variation from specimen to specimen. It is demonstrated, that neither for a cancer prescreening apparatus nor an interactive diagnostic machine, highly differentiated learning sets can be dispensed with. The build-up of the TUDAB learning sets and results of single cell classification, visual reclassification, as well as population analysis and specimen classification are shown.

Cell Physiological Phenomena↗

Structure-based analysis of protein dynamics: comparison of theoretical results for hen lysozyme with X-ray diffraction and NMR relaxation data.

An analytical approach based on Gaussian network model (GNM) is proposed for predicting the rotational dynamics of proteins. The method, previously shown to successfully reproduce X-ray crystallographic temperature factors for a series of proteins is extended here to predict bond torsional mobilities and reorientation of main chain amide groups probed by 15N-H nuclear magnetic resonance (NMR) relaxation. The dynamics of hen egg-white lysozyme (HEWL) in the folded state is investigated using the proposed approach. Excellent agreement is observed between theoretical results and experimental (X-ray diffraction and NMR relaxation) data. The analysis reveals the important role of coupled rotations, or cross-correlations between dihedral angle librations, in defining the relaxation mechanism on a local scale. The crystal and solution structures exhibit some differences in their local motions, but their global motions are identical. Hinge residues mediating the cooperative movements of the alpha- and beta-domains are identified, which comprise residues in helix C, Glu35 and Ser36 on the loop succeeding helix B, Ile55 and Leu56 at the turn between strands II and III. The central part of the beta-domain long loop and the turn between strands I and II display an enhanced mobility. Finally, kinetically hot residues and key interactions are identified, which point at helix B and beta-strand III as the structural elements underlying the stability of the tertiary structure.

Animals↗

The quality of laboratory testing today: an assessment of sigma metrics for analytic quality using performance data from proficiency testing surveys and the CLIA criteria for acceptable performance.

To assess the analytic quality of laboratory testing in the United States, we obtained proficiency testing survey results from several national programs that comply with Clinical Laboratory Improvement Amendments (CLIA) regulations. We studied regulated tests (cholesterol, glucose, calcium, fibrinogen, and prothrombin time) and nonregulated tests (international normalized ratio [INR], glycohemoglobin, and prostate-specific antigen [PSA]). Quality was assessed on the sigma scale with a benchmark for minimum process performance of 3 sigma and a goal for world-class quality of 6 sigma. Based on the CLIA criteria for acceptable performance in proficiency testing (allowable total errors [TEa]), the national quality of cholesterol testing (TEa = 10%) estimated sigma values as 2.9 to 3.0; glucose (TEa = 10%), 2.9 to 3.3; calcium (TEa = 1.0 mg/dL), 2.8 to 3.0; prothrombin time (TEa = 15%), 1.8; INR (TEa = 20%), 2.4 to 3.5; fibrinogen (TEa = 20%), 1.8 to 3.2; glycohemoglobin (TEa = 10%), 1.9 to 2.6; and PSA (TEa = 10%), 1.2 to 1.8. The analytic quality of laboratory tests requires improvement in measurement performance and more intensive quality control monitoring than the CLIA minimum of 2 levels per day.

Benchmarking↗

Simultaneous determination of nafcillin and methicillin by different fluorimetric techniques using partial least-squares calibration.

The simultaneous determination of nafcillin and methicillin was accomplished by constant wavelength synchronous fluorimetry, in combination with partial least-squares multivariate calibration. The total luminescence information of the compounds was used to optimize the spectral data set to perform the calibration. A calibration set of standard samples was designed by combination of a factorial design, with three levels for each factor, and a central composite design. A comparative study of the results obtained using the excitation, the emission, the constant wavelength synchronous and the constant energy synchronous spectral data as analytical signals was performed. The data, set composed of the constant wavelength synchronous spectra, was selected as the analytical signal. The method was successfully applied to the determination of nafcillin and methicillin in mixtures.

Fluorometry↗

Simultaneous fluorimetric determination of acetylsalicylic acid metabolites in urine by partial least squares multivariate calibration.

A method is described for the simultaneous determination of the main urinary acetylsalicylic acid (aspirin) metabolites, salicyclic, salicyluric and gentisic acids, based on their native fluorescence. The urine was extracted into diethyl ether in acid medium, and back-extracted with glycine/sodium hydroxide buffer solution at pH 9.4. A comparative study of the results found using the excitation, the emission and the combination of the excitation plus the emission spectral data, as analytical signals, was performed. The data set, composed of the excitation plus the emission spectra, was selected as the analytical signal. The optimum wavelengths to record the excitation (lambda(em)=444 nm) and the emission spectra (lambda(ex)=323 nm) were selected to maximize the contribution from gentisic acid, which is the minor urinary metabolite. Partial least squares (PLS-1) multivariate calibration was then applied for the determination. Recovery values from urine samples spiked with salicyclic, salicyluric and gentisic acids varied from 90.1 to 97.6% (mean 93.6%), from 90.0 to 110% (mean 97.9%) and from 89.9 to 104.7% (mean 98.5%), respectively.

Journal Article↗

Computing body segment trajectories in the Hybrid III dummy using linear accelerometer data.

An analytical method was developed and tested using several mini-sled and Hyge sled tests to calculate the planar trajectory of a Hybrid III dummy head. Aimed at expediting the Hybrid III test analyses, it may provide an opportunity for cost savings through reduced hardware and manpower on film analyses. Transformation from the moving coordinate to the laboratory coordinate is based on the angular positions integrated from the derived angular accelerations. Gravitational correction of the linear accelerometers was found to be insignificant. The computed head trajectories were compared to the ones obtained from the high speed film images. Accuracy of the calculated head trajectory relies heavily on the accuracy of the computed angular acceleration. Strain-gaged accelerometers are not dependable at all times during an impact and an ill-behaved signal for a very short period may create a significant drift in computed displacement due to double integrations. Accuracy of the currently available accelerometers is not high enough for an angular displacement calculation. A new generation of accelerometers with higher accuracy, or an angular velocity sensor may provide more accurate angular displacement for trajectory analyses. The redundancy of the in-line accelerations helps improve the isolation of erroneous outputs and improve accuracy of the procedure.

Acceleration↗

Development of a biodynamics work environment (BWE) which integrates a biodynamics data bank, models, and analytical tools.

For more than thirty years the Armstrong Laboratory (AL) has studied the response of human volunteers and human surrogates to impact accelerations. Data from these studies form a national resource which should be made available to biodynamics model builders and safety researchers everywhere. Recently AL joined with the National Highway Transportation Safety Administration (NHTSA) to develop a multi-media Biodynamics Work Environment (BWE) which will facilitate access to both their respective data bases and provide a means for sharing that access within the scientific community. The BWE concept is sufficiently flexible to allow integration of other databases as well as biodynamics models and tools. The AL data, for example, consists of over 10,000 impact tests which are currently archived on optical media. Each test includes acceleration and motion time histories, subject anthropometry, documentation photos, and high speed video. Among the models to be included are the Articulated Total Body, Head Spine, Dynamic Response Index, Multi-axis Dynamic Response Criteria, and BURNSIM. Complementary analytical tools would involve the use of spreadsheets, statistics, modeling, data analysis, and math packages. This paper will discuss the development, current status, and future plans of the BWE.

Acceleration↗

Neuroinformatics: the integration of shared databases and tools towards integrative neuroscience.

There is significant interest amongst neuroscientists in sharing neuroscience data and analytical tools. The exchange of neuroscience data and tools between groups affords the opportunity to differently re-analyze previously collected data, encourage new neuroscience interpretations and foster otherwise uninitiated collaborations, and provide a framework for the further development of theoretically based models of brain function. Data sharing will ultimately reduce experimental and analytical error. Many small Internet accessible database initiatives have been developed and specialized analytical software and modeling tools are distributed within different fields of neuroscience. However, in addition large-scale international collaborations are required which involve new mechanisms of coordination and funding. Provided sufficient government support is given to such international initiatives, sharing of neuroscience data and tools can play a pivotal role in human brain research and lead to innovations in neuroscience, informatics and treatment of brain disorders. These innovations will enable application of theoretical modeling techniques to enhance our understanding of the integrative aspects of neuroscience. This article, authored by a multinational working group on neuroinformatics established by the Organization for Economic Co-operation and Development (OECD), articulates some of the challenges and lessons learned to date in efforts to achieve international collaborative neuroscience.

Computational Biology↗

Evaluation of properties of apigenin and [G-3H]apigenin and analytic method development.

This study provides baseline data and analytical methods to assist in the evaluation of apigenin, a plant flavonoid with promising chemopreventive activity against skin cancer. Apigenin was freely soluble in dimethylsulfoxide (> 100 mg/mL), but it had low solubility (0.00135-1.63 mg/mL) in all the other solvents and surfactants tested, especially in highly hydrophilic or nonpolar solvents. The partition coefficient (log K) calculated from the solubility ratio of apigenin in n-octanol and water was 2.87. Apigenin strongly absorbed UV light, with three maximum absorption wavelengths at 212, 269, and 337 nm (epsilon = 29,800, 19,020, and 18,930 M-1 cm-1, respectively). Using quercetin as the internal standard, a reversed-phase HPLC method was developed to quantitatively analyze apigenin in epidermal cells obtained from SENCAR mice. Apigenin was labeled at position 6, 8, 3', and 5' with tritium by a platinum-catalyzed proton-tritium exchange as confirmed indirectly by 1H NMR analysis of the deuterated apigenin. The tritium label was stable in aqueous environments, especially under acidic and neutral conditions, so [G-3H]apigenin was considered suitable for subsequent absorption and metabolic studies.

Animals↗

The role of pilot studies in the economic evaluation of health technologies.

An increasing number of economic evaluations are being conducted alongside clinical trials. While this practice offers the prospect of collecting comprehensive and accurate cost data, it requires considerable time and effort. In the case of clinical data, key analytic decisions such as which data to collect and sample size are often made with reference to smaller (pilot) trials. However, this approach is not normally followed in the case of economic evaluation. This study was based on a recently completed health technology assessment comparing conventional radiotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) for patients with head and neck cancer or carcinoma of the bronchus. In the full health technology assessment, cost data were available for 526 head and neck patients (314 CHART and 212 conventional therapy) and 286 bronchus patients (175 CHART and 109 conventional therapy). In order to simulate a pilot study, data were extracted for the patients recruited to both trials in the first 3 months. These were then compared with the full data set in order to assess whether such a pilot study would have given useful guidance on: a) the usefulness of undertaking a full study; b) the sample size required; and c) the important resource items for which comprehensive data collection would be required. Pilot studies can be helpful in determining the likely advantages of undertaking full economic evaluations and in identifying important resource items. Therefore, it is important that clinical researchers and research funding bodies create the necessary time window to enable such studies to take place. However, formal sample size calculations are more difficult to perform on limited data, since they also require knowledge of the unit cost (or prices) to be attached to the resource items and the correlation between costs and clinical effects.

Bronchial Neoplasms↗

MaizeGDB, the community database for maize genetics and genomics.

The Maize Genetics and Genomics Database (MaizeGDB) is a central repository for maize sequence, stock, phenotype, genotypic and karyotypic variation, and chromosomal mapping data. In addition, MaizeGDB provides contact information for over 2400 maize cooperative researchers, facilitating interactions between members of the rapidly expanding maize community. MaizeGDB represents the synthesis of all data available previously from ZmDB and from MaizeDB-databases that have been superseded by MaizeGDB. MaizeGDB provides web-based tools for ordering maize stocks from several organizations including the Maize Genetics Cooperation Stock Center and the North Central Regional Plant Introduction Station (NCRPIS). Sequence searches yield records displayed with embedded links to facilitate ordering cloned sequences from various groups including the Maize Gene Discovery Project and the Clemson University Genomics Institute. An intuitive web interface is implemented to facilitate navigation between related data, and analytical tools are embedded within data displays. Web-based curation tools for both designated experts and general researchers are currently under development. MaizeGDB can be accessed at http://www.maizegdb.org/.

Computational Biology↗

Establishment of a reference collection of additives and an analytical handbook of reference data to support enforcement of EU regulations on food contact plastics.

A collection has been made of additives that are required as analytical standards for enforcement of European Union legislation on food contact plastics. The 100 additives have been characterized by mass spectrometry, infra-red spectroscopy and proton nuclear magnetic resonance spectroscopy to provide reference spectra. Gas chromatographic retention times have been recorded to facilitate identification by retention index. This information has been further supplemented by physico-chemical data. Finally, chromatographic methods have been used to indicate the presence of any impurities in the commercial chemicals. Samples of the reference substances are available on request and the collection of spectra and other information will be made available in printed format and on-line through the Internet. This paper gives an overview of the work done to establish the reference collection and the spectral atlas, which together will assist enforcement laboratories in the characterization of plastics and the selection of analytical methods for additives that may migrate.

Chromatography, Gas↗

ArrayCluster: an analytic tool for clustering, data visualization and module finder on gene expression profiles.

SUMMARY: One of the significant challenges in gene expression analysis is to find unknown subtypes of several diseases at the molecular levels. This task can be addressed by grouping gene expression patterns of the collected samples on the basis of a large number of genes. Application of commonly used clustering methods to such a dataset however are likely to fail owing to over-learning, because the number of samples to be grouped is much smaller than the data dimension which is equal to the number of genes involved in the dataset. To overcome such difficulty, we developed a novel model-based clustering method, referred to as the mixed factors analysis. The ArrayCluster is a freely available software to perform the mixed factors analysis. It provides us some analytic tools for clustering DNA microarray experiments, data visualization and an automatic detector for module transcriptional of genes that are relevant to the calibrated molecular subtypes and so on.

Bayes Theorem↗

Establishment of a reference collection of substances and an analytical handbook of reference data to support enforcement of EC regulations on food contact materials.

A collection has been made of monomers and other starting substances that are required as analytical standards for enforcement of European Community legislation on food contact materials. The substances have been analysed by mass spectrometry and appropriate chromatographic methods to indicate the presence of impurities. The collection has been supplemented by a database of infra-red and mass spectra, and a handbook that collates various information to assist enforcement laboratories in the identification of plastics articles and the selection of appropriate methods of analysis where these are available.

Databases, Factual↗

How gap genes make their domains: An analytical study based on data driven approximations.

We consider a mathematical formulation of the problem of protein production during segment determination in the Drosophila blastoderm, together with some preliminary results of its analytical study. We reformulate the spatial difference equations as a set of nonlinear partial differential equations and obtain their dimensionless form in the continuum limit. Using previous results obtained by the gene circuit method, we find an asymptotic statement of the problem with a small parameter. Some results of the comparison method applied to the model are obtained, and exact stationary upper solutions are derived. They exhibit distinctive features of localized bell-shaped structures. (c) 2001 American Institute of Physics.

Journal Article↗

Using large data bases in nursing and health policy research.

Concern about the quality, cost, and outcomes of health care has become a driving force in health policy research. The growing accessibility of large clinical and administrative health care data bases has led to an interest in using such data in health policy research. Clinical data bases are created by providers of care and contain data about episodes and outcomes of care, usually organized as patient records. Administrative data bases contain data about indirect care processes such as insurance claims processing, vital event recording, and quality assurance. Clinical and administrative data bases may contain millions of records, consist of data from multiple sites, and often have missing data issues that must be considered by researchers. These and other characteristics of large data bases require special data manipulation and analytic techniques. Large data bases have been used in epidemiological studies, risk assessment, and technology assessment and to study variations in caregiver practice patterns. Because the use of large data bases by nurse researchers has been constrained by the lack of nursing-relevant data in them, there is a need to reach consensus on useful and feasible nursing data elements and to include those data in ongoing data collection efforts by government agencies and private organizations.

Bias↗