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Methods for analyzing health care utilization and costs.

Important questions about health care are often addressed by studying health care utilization. Utilization data have several characteristics that make them a challenge to analyze. In this paper we discuss sources of information, the statistical properties of utilization data, common analytic methods including the two-part model, and some newly available statistical methods including the generalized linear model. We also address issues of study design and new methods for dealing with censored data. Examples are presented.

Data Interpretation, Statistical↗

Estrogen therapy in postmenopausal women: effects on cognitive function and dementia.

CONTEXT: Several studies have suggested that estrogen replacement therapy in postmenopausal women improves cognition, prevents development of dementia, and improves the severity of dementia, while other studies have not found a benefit of estrogen use. OBJECTIVE: To determine whether postmenopausal estrogen therapy improves cognition, prevents development of dementia, or improves dementia severity. DATA SOURCES: We performed a literature search of studies published from January 1966 through June 1997, using MEDLINE, manually searched bibliographies of articles identified, and consulted experts. STUDY SELECTION: Studies that evaluated biological mechanisms of estrogen's effect on the central nervous system and studies that addressed the effect of estrogen on cognitive function or on dementia. DATA EXTRACTION: We reviewed studies for methods, sources of bias, and outcomes and performed a meta-analysis of the 10 studies of postmenopausal estrogen use and risk of dementia using standard meta-analytic methods. DATA SYNTHESIS: Biochemical and neurophysiologic studies suggest several mechanisms by which estrogen may affect cognition: promotion of cholinergic and serotonergic activity in specific brain regions, maintenance of neural circuitry, favorable lipoprotein alterations, and prevention of cerebral ischemia. Five observational studies and 8 trials have addressed the effect of estrogen on cognitive function in nondemented postmenopausal women. Cognition seems to improve in perimenopausal women, possibly because menopausal symptoms improve, but there is no clear benefit in asymptomatic women. Ten observational studies have measured the effect of postmenopausal estrogen use on risk of developing dementia. Meta-analysis of these studies suggests a 29% decreased risk of developing dementia among estrogen users, but the findings of the studies are heterogeneous. Four trials of estrogen therapy in women with Alzheimer disease have been conducted and have had primarily positive results, but most have been small, of short duration, non-randomized, and uncontrolled. CONCLUSIONS: There are plausible biological mechanisms by which estrogen might lead to improved cognition, reduced risk for dementia, or improvement in the severity of dementia. Studies conducted in women, however, have substantial methodologic problems and have produced conflicting results. Large placebo-controlled trials are required to address estrogen's role in prevention and treatment of Alzheimer disease and other dementias. Given the known risks of estrogen therapy, we do not recommend estrogen for the prevention or treatment of Alzheimer disease or other dementias until adequate trials have been completed.

Alzheimer Disease↗

Modelling of light pollution in suburban areas using remotely sensed imagery and GIS.

This paper describes a methodology for modelling light pollution using geographical information systems (GIS) and remote sensing (RS) technology. The proposed approach attempts to address the issue of environmental assessment in sensitive suburban areas. The modern way of life in developing countries is conductive to environmental degradation in urban and suburban areas. One specific parameter for this degradation is light pollution due to intense artificial night lighting. This paper aims to assess this parameter for the Athens metropolitan area, using modern analytical and data capturing technologies. For this purpose, night-time satellite images and analogue maps have been used in order to create the spatial database of the GIS for the study area. Using GIS advanced analytical functionality, visibility analysis was implemented. The outputs for this analysis are a series of maps reflecting direct and indirect light pollution around the city of Athens. Direct light pollution corresponds to optical contact with artificial night light sources, while indirect light pollution corresponds to optical contact with the sky glow above the city. Additionally, the assessment of light pollution in different periods allows for dynamic evaluation of the phenomenon. The case study demonstrates high levels of light pollution in Athens suburban areas and its increase over the last decade.

Air Pollutants↗

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↗

Metabolic heterogeneity of low density lipoprotein-apoB production in familial hypercholesterolemia: an analytical model solution of tracer data.

Six subjects with heterozygous familial hypercholesterolemia (FH) (three males, three females) formed the basis for an investigation of the pathways of production of apoprotein B within plasma low-density-lipoprotein (LDL-apoB). Following the intravenous injection of [75Se]selenomethionine as an amino acid tracer, incorporation of the radioactive isotope into the putative precursor of LDL, intermediate density lipoprotein (IDL-apoB), was examined over a 9-day period. The resulting tracer data provided the precursor profile for both the IDL catabolic conversion of LDL as well as for direct synthesis of LDL from amino acids. The fractional conversion rates, (beta) for IDL and (alpha) for amino acids to LDL-apoB, were determined utilizing the two-compartment model for LDL involving both the intravascular and the extravascular pools of apoB. This LDL model was resolved analytically and the parameters alpha and beta were determined so as to give the least squares fit to the LDL tracer data. In this solution, the fractional conversion rates of IDL and of amino acids to LDL-apoB were resolved with a mean fractional residual of 20 +/- 6%, which was randomly distributed within the LDL-apoB data throughout the 216 hours of the studies. The steady-state determination of the pathways of LDL-apoB synthesis, based upon this tracer analysis, indicate that IDL accounts for 46%, and amino acids account for 54% of total apoB production within plasma LDL in heterozygous FH. In contrast, in normal subjects, IDL accounts for 86% of total LDL-apoB production. Since the IDL catabolic pathway represents the predominant if not exclusive source of LDL in normal man, this demonstration of a major non-IDL source of LDL in FH broadens the understanding of the pathophysiology of human familial hypercholesterolemia.

Adult↗

The Horwitz ratio (HorRat): A useful index of method performance with respect to precision.

The Horwitz ratio (HorRat) is a normalized performance parameter indicating the acceptability of methods of analysis with respect to among-laboratory precision (reproducibility). It is the ratio of the observed relative standard deviation among laboratories calculated from the actual performance data, RSDR (%), to the corresponding predicted relative standard deviation calculated from the Horwitz equation PRSDR (%) = 2C(-0.15), where C is the concentration found or added, expressed as a mass fraction. It is more or less independent of analyte, matrix, method, and time of publication (as a surrogate for the state of the art of analytical chemistry). It is now one of the acceptability criteria for many of the recently adopted chemical methods of analysis of AOAC INTERNATIONAL, the European Union, and other European organizations dealing with food analysis (e.g., European Committee for Standardization and Nordic Analytical Committee). The origin and applications of the formula are described. Consistent deviations from the ratio on the low side (values <0.5) may indicate unreported averaging or excellent training and experience; consistent deviations on the high side (values >2) may indicate inhomogeneity of the test samples, need for further method optimization or training, operating below the limit of determination, or an unsatisfactory method.

Chemistry Techniques, Analytical↗

A dynamic electrical record of the pathway of human His bundle activation from surface mapping.

Body surface potential maps of human His bundle activity have been difficult to product for two reasons: (1) The peak surface potentials are often less than 5 muv, and (2) the simultaneous atrial repolarization potentials frequently exceed 100 muv. We have therefore amplified surface signals 25 times the standard gain of 1000, and then removed by cross-correlation the static pattern of atrial repolarization for serial 1-msec maps of the P-R segment in five normal men. A consistent finding emerged: a positive anterior chest peak appeared 40 msec before QRS onset, and then-within 10 msec-spread out into a long, low transverse mound before disappearing in 5 more msec. The map data were analytically converted to serial electrical sources: the center of electrical activity moved first slightly down, then directly forward, before retracing its path and disappearing. The retrace and accompanying surface spread-out strongly suggests diverging dipolar sources. Thus the data fit a simple heart source which moves anteriorly and then breaks into two (right and left)-as expected from activation of the bundle of His and its bifurcation into left and right bundle branches.

Action Potentials↗

SPf66 vaccine trial in Brazil: conceptual framework study design and analytical approach.

This paper describes the study population and the study design of the phase III field trail of the SPf66 vaccine in Brazil. Assessment of validity and precision principles necessary for the appropriate evaluation of the protective effect of the vaccine are discussed, as well as the results of the preliminary analyses of the gathered data. The analytical approach for the estimation of the protective effect of the vaccine is presented. This paper provides the conceptual framework for future publications.

Adolescent↗

Isotope abundance analysis methods and software for improved sample identification with supersonic gas chromatography/mass spectrometry.

We present newly developed isotope abundance analysis (IAA) methods and software which are used to derive elemental formula information from experimental mass spectral data of molecular ion isotopomeric abundances. The software, using a novel method, can also be used to automatically confirm or reject NIST library search results, thereby significantly improving the confidence level in sample identifications. In the case of IAA confirmation of the NIST library results, sample identification is unambiguous, since the confirmation is achieved by two independent sets of data and analytical methods. In the case of a rejection, such as when the molecule is not included in the library's databases, the IAA software independently provides a list of elemental formulae with declining order of matching to the isotopomeric experimental data, in a similar way to accurate mass measurements with costly instruments. IAA is ideally applicable to gas chromatography/mass spectrometry (GC/MS) (and liquid chromatography/electron ionization mass spectrometry (LC/EI-MS)) with a supersonic molecular beam (SMB) since it requires a trustworthy and highly abundant true molecular ion that is unique to the SMB-MS systems, plus the absence of self chemical ionization and vacuum background noise, again unique features of GC/SMB-MS. The various features of the IAA methods and software are described, their performance is demonstrated with the analysis of experimental GC-SMB-MS data and the IAA concept is compared with accurate mass alternatives. The combination of IAA and GC/SMB-MS is believed to be superior to accurate mass GC/MS in view of the general availability of trustworthy molecular ions for an extended range of compounds.

Journal Article↗

The H4IIE cell bioassay as an indicator of dioxin-like chemicals in wildlife and the environment.

The H4IIE cell bioassay has proven utility as a screening tool for planar halogenated hydrocarbons (PHHs) and structurally similar chemicals accumulated in organisms from the wild. This bioassay has additional applications in hazard assessment of PHH exposed populations. In this review, the toxicological principles, current protocols, performance criteria, and field applications for the assay are described. The H4IIE cell bioassay has several advantages over the analytical measurement of PHHs in environmental samples, but conclusions from studies can be strengthened when both bioassay and analytical chemistry data are presented together. Often, the bioassay results concur with biological effects in organisms and support direct measures of PHHs. For biomonitoring purposes and prioritization of PHH-contaminated environments, the H4IIE bioassay may be faster and less expensive than analytical measurements. The H4IIE cell bioassay can be used in combination with other biomarkers such as in vivo measurements of CYP1A1 induction to help pinpoint the sources and identities of dioxin-like chemicals. The number of studies that measure H4IIE-derived TCDD-EQs continues to increase, resulting in subtle improvements over time. Further experiments are required to determine if TCDD-EQs derived from mammalian cells are adequate predictors of toxicity to non-mammalian species. The H4IIE cell bioassay has been used in over 300 published studies, and its combination of speed, simplicity, and ability to integrate the effects of complex contaminant mixtures makes it a valuable addition to hazard assessment and biomonitoring studies.

Animals↗

Chemometric investigation of some analytical methods used for the chemical test of foetal lung maturity.

The lecithin/sphingomyelin (L/S) ratio is particularly important for the prediction of foetal lung maturity. A package for pattern recognition of analytical chemical data, "Parvus", was used to handle the different values of the L/S ratio obtained experimentally by common amperometric, spectrometric and chromatographic methods for the determination of lecithin. Eight subjects were considered and some interesting conclusions drawn on the equivalence of different analytical methods of determining lecithin in amniotic fluid.

Adult↗

Cluster analysis of activity-time series in motor learning.

Neuroimaging studies of learning focus on brain areas where the activity changes as a function of time. To circumvent the difficult problem of model selection, we used a data-driven analytic tool, cluster analysis, which extracts representative temporal and spatial patterns from the voxel-time series. The optimal number of clusters was chosen using a cross-validated likelihood method, which highlights the clustering pattern that generalizes best over the subjects. Data were acquired with PET at different time points during practice of a visuomotor task. The results from cluster analysis show practice-related activity in a fronto-parieto-cerebellar network, in agreement with previous studies of motor learning. These voxels were separated from a group of voxels showing an unspecific time-effect and another group of voxels, whose activation was an artifact from smoothing.

Adult↗

Using voxel-specific hemodynamic response function in EEG-fMRI data analysis.

Most existing analytical techniques for EEG-fMRI data need specific assumptions about the hemodynamic response function (HRF). These assumptions may not be appropriate when the HRF varies from subject to subject or from region to region. In this article, we introduce a deconvolution method for EEG-fMRI activation detection, which can be implemented with voxel-specific HRFs. A comparison of performance is made between three fixed HRFs and the deconvolution method under the framework of the general linear model. The main results are as follows: (1) the volume of detected regions from the deconvolved HRFs is larger. (2) In some subjects, the deconvolution technique can find areas of activation that have not been detected with the three fixed HRFs at our threshold of significance. (3) Deconvolution obtained higher adjusted coefficients of multiple determination compared to those obtained with the three fixed HRFs. The results suggest that the fixed HRF methods may not be the most appropriate for the analysis of epileptic activity with EEG-fMRI, and the deconvolution method may be a better choice.

Brain↗

A class of models for analyzing GeneChip gene expression analysis array data.

BACKGROUND: Various analytical methods exist that first quantify gene expression and then analyze differentially expressed genes from Affymetrix GeneChip gene expression analysis array data. These methods differ in the choice of probe measure (quantification of probe hybridization), summarizing multiple probe intensities into a gene expression value, and analysis of differential gene expression. Research papers that describe these methods focus on performance, and how their approaches differ from others. To better understand the common features and differences between various methods, and to evaluate their impact on the results of gene expression analysis, we describe a class of models, referred to as generalized probe models (GPMs), which encompass various currently available methods. RESULTS: Using an empirical dataset, we compared different formulations of GPMs, and GPMs with three other commonly used methods, i.e. MAS 5.0, dChip, and RMA. The comparison shows that, on a genome-wide scale , different methods yield similar results if the same probe measures are chosen. CONCLUSION: In this paper we present a general framework, i.e. GPMs, which encompasses various methods. GPMs permit the use of a wide range of probe measures and facilitate appropriate comparison between commonly used methods. We demonstrate that the dissimilar results stem primarily from different choice of probe measures, rather than other factors.

Algorithms↗

Factor analytic approaches to personality item-level data.

Factor analysis models have played a central role in formulating conceptual models in personality and personality assessment, as well as in empirical examinations of personality measurement instruments. Yet, the use of item-level data presents special problems for factor analysis, applications. In this article, we review recent developments in factor analysis that are appropriate for the type of item-level data often collected in personality. Included in this review are discussions of how these developments have been addressed in the context of two different (but formally related) statistical models item response theory (IRT: Hambleton, Swaminathan, & Rogers, 1991) and structural, equation modeling (Bollen 1989) for item-level data. We also discuss the relevance of item scaling in the context of these models. Using the restandardization data for the Minnesota Multiphasic Personality Inventory-2 Scale (cf. Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989), we show brief examples of the utility of these approaches to address basic questions about responses to personality scale items regarding: (a) scale, dimensionality and general item properties, (b) the "appropriateness" of the observed responses, and (c) differential item functioning across subsamples. implications for analyses of personality item-level data in the IRT and factor analytic traditions are discussed.

Journal Article↗

Insulin pump therapy: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis of the metabolic and psychosocial impact of continuous subcutaneous insulin infusion (CSII) therapy on adults, adolescents, and children. RESEARCH DESIGN AND METHODS: Studies were identified and data regarding study design, year of publication, sample size, patient's age, diabetes duration, and duration of CSII therapy were collected. Means and SDs for glycohemoglobin, blood glucose, insulin dosages, and body weight for CSII and comparison conditions were subjected to meta-analytic procedures. Data regarding pump complications and psychosocial functioning were reviewed descriptively. RESULTS: A total of 52 studies, consisting of 1,547 patients, were included in the meta-analysis. Results indicate that CSII therapy is associated with significant improvements in glycemic control (decreased glycohemoglobin and mean blood glucose). A descriptive review of potential complications of CSII use (e.g., hypoglycemia, diabetic ketoacidosis [DKA], pump malfunction, and site infections) suggests a decreased frequency of hypoglycemic episodes but an increased frequency of DKA in studies published before 1993. CONCLUSIONS: CSII therapy is associated with improved glycemic control compared with traditional insulin therapies (conventional therapy and multiple daily injections) and does not appear to be associated with significant adverse outcomes. Additional studies are needed to further examine the relative risks of CSII therapy, including the potential psychosocial impact of this technologically advanced therapy.

Age Factors↗

Analytic webs support the synthesis of ecological data sets.

A wide variety of data sets produced by individual investigators are now synthesized to address ecological questions that span a range of spatial and temporal scales. It is important to facilitate such syntheses so that "consumers" of data sets can be confident that both input data sets and synthetic products are reliable. Necessary documentation to ensure the reliability and validation of data sets includes both familiar descriptive metadata and formal documentation of the scientific processes used (i.e., process metadata) to produce usable data sets from collections of raw data. Such documentation is complex and difficult to construct, so it is important to help "producers" create reliable data sets and to facilitate their creation of required metadata. We describe a formal representation, an "analytic web," that aids both producers and consumers of data sets by providing complete and precise definitions of scientific processes used to process raw and derived data sets. The formalisms used to define analytic webs are adaptations of those used in software engineering, and they provide a novel and effective support system for both the synthesis and the validation of ecological data sets. We illustrate the utility of an analytic web as an aid to producing synthetic data sets through a worked example: the synthesis of long-term measurements of whole-ecosystem carbon exchange. Analytic webs are also useful validation aids for consumers because they support the concurrent construction of a complete, Internet-accessible audit trail of the analytic processes used in the synthesis of the data sets. Finally we describe our early efforts to evaluate these ideas through the use of a prototype software tool, SciWalker. We indicate how this tool has been used to create analytic webs tailored to specific data-set synthesis and validation activities, and suggest extensions to it that will support additional forms of validation. The process metadata created by SciWalker is readily adapted for inclusion in Ecological Metadata Language (EML) files.

Data Collection↗

New approach to IR study of monomer-dimer self-association: 2,2-dimethyl-3-ethyl-3-pentanol in tetrachloroethylene as an example.

The dimerization of 2,2-dimethyl-3-ethyl-3-pentanol in tetrachloroethylene in the diluted region has been studied at four temperatures by IR spectroscopy. The aforementioned solute compound is chosen because self-association beyond dimerization is hampered by the steric hindrance generated by the bulky sidechains. The integrated absorbances of the monomer bands were treated based on Eq. (9) to obtain its molar absorptivity and dimerization constant. The same dimerization constant as well as the molar absorptivity of dimer band can be obtained based on Eq. (13) from the data treatment of the integrated absorbances of the dimer band. The disparity between two values of dimerization constant determined by two independent sources offers an opportunity to check the consistency of the determination. The standard enthalpy and entropy of dimerization have also been calculated by means of van't Hoff plot, respectively, from the data of temperature-dependent dimerization constants obtained from the monomer bands and dimer bands.

Chemistry Techniques, Analytical↗