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PubMed2001

Measurement uncertainty of thermodynamic data.

Thermodynamic quantities of chemical reactions are commonly derived from experimental data obtained by chemical analysis. The accuracy of the evaluated thermodynamic quantities is limited by the measurement uncertainty of the analytical techniques applied. Straightforward transfer of metrological rules established for determination of single analytes to the more complex process of evaluating values of thermodynamic quantities is not possible. Computer-intensive statistical methods and Monte Carlo techniques are shown to enable integration of existing metrological concepts. An initial stage of the integration of both concepts is presented, taking solubility data for Am(III) in carbonate media as an illustrative example. A cause and effect diagram is created as a means of identification of sources of uncertainty. The uncertainties are used in a resampling-based Monte Carlo study to produce a probability distribution of the value of a quantity.

Journal Article↗

PubMed1993

Chemistry with confidence: should Clinical Chemistry require confidence intervals for analytical and other data?

Confidence intervals are not commonly provided with analytical or other data reported in Clinical Chemistry although P values are. However, confidence intervals provide an explicit demonstration of the direction and magnitude of uncertainty and are intuitively easy to grasp, unlike P values. It is therefore argued that the Journal should adopt a policy requiring the provision of confidence intervals. Such a policy would improve the statistical rigor of Journal reports.

Chemistry, Clinical↗

PubMed2001

Common factor models of validity and reliability for use with ordinal data in k x k tables.

Three common factor models are proposed for the analysis of k x k ordinal data arising from test validity or reliability situations. These models represent an extension of the polychoric correlation model and item response theory. Identification is complete in the most usual reliability situation, where data from only two indicators (raters) are available. Full maximum likelihood estimation is available together with associated informative deviance tests and goodness-of-fit tests, examples of which are provided.

Data Interpretation, Statistical↗

PubMed1997

AAEM minimonograph #47: normative data in electrodiagnostic medicine. ff.

This article reviews, without mathematics, the important principles governing the acquisition and use of normative data in electrodiagnostic medicine. Common flaws in neurophysiological normative data include vague clinical criteria for establishing freedom from disease, samples that are too small and inadequately stratified, and application of Gaussian statistics to non-Gaussian variables. Other problematic issues concern the trade-off between permissible false-positivity and false-negativity in defining the limits of normative from sample data, test-retest variability, and the use of multiple independent test measurements in each electrodiagnostic examination. The following standards for normative data are proposed: (1) standardized objective determination of freedom from disease; (2) appropriately large sample of normal subjects; (3) proportional statification of normal subjects for known relevant variables; (4) test of Gaussian fit for application of Gaussian statistics; and (5) data presentation by percentiles when Gaussian fit is in doubt. Many existing normative studies in clinical neurophysiology do not meet these standards. High-quality normative data, readily accessible, is essential for the accurate electrodiagnosis of neuromuscular diseases.

Electromyography↗

PubMed2002

Complete imputation of missing repeated categorical data: one-sample applications.

Longitudinal studies with repeated measures are often subject to non-response. Methods currently employed to alleviate the difficulties caused by missing data are typically unsatisfactory, especially when the cause of the missingness is related to the outcomes. We present an approach for incomplete categorical data in the repeated measures setting that allows missing data to depend on other observed outcomes for a study subject. The proposed methodology also allows a broader examination of study findings through interpretation of results in the framework of the set of all possible test statistics that might have been observed had no data been missing. The proposed approach consists of the following general steps. First, we generate all possible sets of missing values and form a set of possible complete data sets. We then weight each data set according to clearly defined assumptions and apply an appropriate statistical test procedure to each data set, combining the results to give an overall indication of significance. We make use of the EM algorithm and a Bayesian prior in this approach. While not restricted to the one-sample case, the proposed methodology is illustrated for one-sample data and compared to the common complete-case and available-case analysis methods.

Algorithms↗

PubMed2003

A mixture model approach to detecting differentially expressed genes with microarray data.

An exciting biological advancement over the past few years is the use of microarray technologies to measure simultaneously the expression levels of thousands of genes. The bottleneck now is how to extract useful information from the resulting large amounts of data. An important and common task in analyzing microarray data is to identify genes with altered expression under two experimental conditions. We propose a nonparametric statistical approach, called the mixture model method (MMM), to handle the problem when there are a small number of replicates under each experimental condition. Specifically, we propose estimating the distributions of a t -type test statistic and its null statistic using finite normal mixture models. A comparison of these two distributions by means of a likelihood ratio test, or simply using the tail distribution of the null statistic, can identify genes with significantly changed expression. Several methods are proposed to effectively control the false positives. The methodology is applied to a data set containing expression levels of 1,176 genes of rats with and without pneumococcal middle ear infection.

Animals↗

PubMed2002

Nonrigid registration of 3D tensor medical data.

New medical imaging modalities offering multi-valued data, such as phase contrast MRA and diffusion tensor MRI, require general representations for the development of automated algorithms. In this paper we propose a unified framework for the registration of medical volumetric multi-valued data using local matching. The paper extends the usual concept of similarity between two pieces of data to be matched, commonly used with scalar (intensity) data, to the general tensor case. Our approach to registration is based on a multiresolution scheme, where the deformation field estimated in a coarser level is propagated to provide an initial deformation in the next finer one. In each level, local matching of areas with a high degree of local structure and subsequent interpolation are performed. Consequently, we provide an algorithm to assess the amount of structure in generic multi-valued data by means of gradient and correlation computations. The interpolation step is carried out by means of the Kriging estimator, which provides a novel framework for the interpolation of sparse vector fields in medical applications. The feasibility of the approach is illustrated by results on synthetic and clinical data.

Algorithms↗

PubMed1991

Interpretation of results with the 8-azaguanine resistance system in Salmonella typhimurium: no evidence for direct acting mutagenesis by 15-oxosteviol, a possible metabolite of steviol.

15-Oxosteviol, postulated to be the mutagenic metabolite of steviol, was observed to be non-mutagenic in preliminary experiments using a number of different systems. Repetition of the original experiment in Salmonella TM677 failed to show any significant induction of 8-azaguanine resistant mutants by 15-oxosteviol even when the number of bacteria tested was greatly increased. Examination of the earlier positive result showed that it could not be justified from the data and revealed a commonly applied way of mishandling data obtained with the TM677 system.

Azaguanine↗

PubMed2002

Experimental verification of overdispersion in radioassay data.

New evidence is provided suggesting that radioassay data are frequently overdispersed with respect to the Poisson distribution. Twelve cases of radioassay data were measured using commonly available detection systems. The data were analyzed using a limited version of the overdispersion model developed earlier. In that limit, the relationships between three overdispersed distributions were derived and discussed: beta-Poisson, negative binomial, and overdispersed Gaussian. Out of a total of 13 cases studied (12 measured plus one from the literature), 4 were consistent with the Poisson statistics at 90% confidence level while the remaining 9 were found overdispersed. This shows that the overdispersion is rather prevalent in radioassay. All three overdispersed distributions fitted the data very well. The overdispersion was attributed mostly to the excess fluctuations of the detection systems or, in 2 cases, sequential radioactive decay.

Models, Statistical↗

PubMed1996

Bacteriocin Typing of Burkholderia (Pseudomonas) solanacearum Race 1 of the French West Indies and Correlation with Genomic Variation of the Pathogen.

Burkholderia solanacearum race 1 isolates indigenous to the French West Indies were characterized by bacteriocin typing and two genomic fingerprinting methods: pulsed-field gel electrophoresis of genomic DNA digested by rare-cutting restriction endonucleases (RC-PFGE) and PCR with primers corresponding to repetitive extragenic palindromic (REP), enterobacterial repetitive intergenic consensus (ERIC), and BOX elements (collectively known as rep-PCR). The survey comprised 24 reference strains and 65 isolates obtained from a field trial in Guadeloupe in 1993. Comparison of the data identified RC-PFGE as the most discriminatory method, delineating 17 pulsed-field gel profile types. rep-PCR and bacteriocin typing identified nine rep-PCR profile types and nine bacteriocin groups. Independent determination of similarity coefficients and clustering of RC-PFGE and rep-PCR data identified six groups common to both sets of data that correlated to biovar and bacteriocin groups. Further study of bacteriocin production in planta gave results consistent with in vitro bacteriocin typing. It was observed that spontaneous bacteriocin-resistant mutants exhibited a cross-resistance to other bacteriocins as identified by the typing scheme and that such mutants possessed a selective advantage for growth over isogenic nonmutants in the presence of a bacteriocin. The results are significant in the search for biological control of disease by nonpathogenic mutants of the wild-type organism.

Journal Article↗

PubMed2005

The role of proxy information in missing data analysis.

This article investigates the role of proxy data in dealing with the common problem of missing data in clinical trials using repeated measures designs. In an effort to avoid the missing data situation, some proxy information can be gathered. The question is how to treat proxy information, that is, is it always better to utilize proxy information when there are missing data? A model for repeated measures data with missing values is considered and a strategy for utilizing proxy information is developed. Then, simulations are used to compare the power of a test using proxy to simply utilizing all available data. It is concluded that using proxy information can be a useful alternative when such information is available. The implications for various clinical designs are also considered and a data collection strategy for efficiently estimating parameters is suggested.

Canada↗

PubMed2005

What is required to evaluate the impact of pharmaceutical reference pricing?

OBJECTIVE: To describe empirical studies evaluating the impact of reference pricing (RP) interventions in pharmaceutical markets in order to discuss the requirements for these evaluations. METHODS: Ten studies were included in this review. For each study, the nature of the intervention, the nature of the data available, the nature of the question to be answered and the requirements of the evaluation method were examined through a questionnaire. The most frequently used evaluation method was the conventional before-after estimator, and only three studies used the difference-in-differences method. RESULTS: Nine studies evaluated a therapeutic RP system and one evaluated a generic RP system. All of the papers reported how the reference price level was established, but only one study directly reported the updating frequency and criteria of the RP system. In four studies, details of simultaneous interventions were not reported. There is no paper providing evidence on overall social welfare impact. Four papers estimated the impact of intervention on the consumer price of drugs covered by the RP system. Only one provided information about the impact on the price of related drugs not covered by the system. Three studies included an outcome variable for the use of health services. The impact of RP intervention on the level of competition in the market for those medicines covered by the system was reported in only three of ten papers. DISCUSSION/CONCLUSION: Despite the rigorous effort made to evaluate the impact of RP policies in some countries, several limitations may affect both their internal validity (the nature of the data available, statistical problems common to non-experimental data, etc.) and their external validity (heterogeneity in the nature of the intervention).

Cost Control↗

PubMed2004

Missing covariate data within cancer prognostic studies: a review of current reporting and proposed guidelines.

Prognostic models play a crucial role in the clinical decision-making process. Unfortunately, missing covariate data impede the construction of valid and reliable models, potentially introducing bias, if handled inappropriately. The extent of missing covariate data within reported cancer prognostic studies, the current handling and the quality of reporting this missing covariate data are unknown. Therefore, a review was conducted of 100 articles reporting multivariate survival analyses to assess potential prognostic factors, published within seven cancer journals in 2002. Missing covariate data is a common occurrence in studies performing multivariate survival analyses, being apparent in 81 of the 100 articles reviewed. The percentage of eligible cases with complete data was obtainable in 39 articles, and was <90% in 17 of these articles. The methods used to handle incomplete covariates were obtainable in 32 of the 81 articles with known missing data and the most commonly reported approaches were complete case and available case analysis. This review has highlighted deficiencies in the reporting of missing covariate data. Guidelines for presenting prognostic studies with missing covariate data are proposed, which if followed should clarify and standardise the reporting in future articles.

Decision Making↗

PubMed2002

Ocean-color optical property data derived from the Japanese Ocean Color and Temperature Scanner and the French Polarization and Directionality of the Earth's Reflectances: a comparison study.

We describe our efforts to study and compare the ocean-color data derived from the Japanese Ocean Color and Temperature Scanner (OCTS) and the French Polarization and Directionality of the Earth's Reflectances (POLDER). OCTS and POLDER were both on board Japan's Sun-synchronous Advanced Earth Observing Satellite from August 1996 to June 1997, collecting approximately 10 months of global ocean-color data. This operation provided a unique opportunity for the development of methods and strategies for the merging of ocean-color data from multiple ocean-color sensors. We describe our approach to the development of consistent data-processing algorithms for both OCTS and POLDER and the use of a common in situ data set to calibrate vicariously the two sensors. Therefore the OCTS- and POLDER-measured radiances are bridged effectively through common in situ measurements. With this approach to the processing of data from two different sensors, the only differences in the derived products from OCTS and POLDER are the differences that are inherited from the instrument characteristics. Results show that there are no obvious bias differences between the OCTS- and POLDER-derived ocean-color products, whereas the differences due to noise, which stem from variations in sensor characteristics, are difficult to correct at the pixel level. The ocean-color data from OCTS and POLDER therefore can be compared and merged in the sense that there is no significant bias between two.

Journal Article↗

PubMed2000

Use of a secure Internet Web site for collaborative medical research.

Researchers who collaborate on clinical research studies from diffuse locations need a convenient, inexpensive, secure way to record and manage data. The Internet, with its World Wide Web, provides a vast network that enables researchers with diverse types of computers and operating systems anywhere in the world to log data through a common interface. Development of a Web site for scientific data collection can be organized into 10 steps, including planning the scientific database, choosing a database management software system, setting up database tables for each collaborator's variables, developing the Web site's screen layout, choosing a middleware software system to tie the database software to the Web site interface, embedding data editing and calculation routines, setting up the database on the central server computer, obtaining a unique Internet address and name for the Web site, applying security measures to the site, and training staff who enter data. Ensuring the security of an Internet database requires limiting the number of people who have access to the server, setting up the server on a stand-alone computer, requiring user-name and password authentication for server and Web site access, installing a firewall computer to prevent break-ins and block bogus information from reaching the server, verifying the identity of the server and client computers with certification from a certificate authority, encrypting information sent between server and client computers to avoid eavesdropping, establishing audit trails to record all accesses into the Web site, and educating Web site users about security techniques. When these measures are carefully undertaken, in our experience, information for scientific studies can be collected and maintained on Internet databases more efficiently and securely than through conventional systems of paper records protected by filing cabinets and locked doors. JAMA. 2000;284:1843-1849.

Computer Security↗

PubMed2003

Maintaining data integrity in microarray data management.

Gene expression microarrays are a relatively new technology, dating back just a few years, yet they have already become a very widely used tool in biology, and have evolved to a wide range of applications well beyond their original design intent. However, while the use of microarrays has expanded, and the issues of performance optimization have been intensively studied, the fundamental issue of data integrity management has largely been ignored. Now that performance has improved so greatly, the shortcomings of data integrity control methods constitute a greater percent of the stumbling blocks for investigators. Microarray data are cumbersome, and the rule up to this point has mostly been one of hands-on transformations, leading to human errors which often have dramatic consequences. We show in this review that the time lost on such mistakes is enormous and dramatically affects results; therefore, mistakes should be mitigated in any way possible. We outline the scope of the data integrity issue, to survey some of the most common and dangerous data transformations, and their shortcomings. To illustrate, we review some case studies. We then look at the work done by the research community on this issue (which admittedly is meager up to this point). Some data integrity issues are always going to be difficult, while others will become easier-one of our goals is to expedite the use of integrity control methods. Finally, we present some preliminary guidelines and some specific approaches that we believe should be the focus of future research.

Algorithms↗

PubMed2001

Transmission/disequilibrium test analysis of total serum IgE levels in the Hutterite and Collaborative Study on the Genetics of Asthma data sets.

The Hutterite and Collaborative Study on the Genetics of Asthma data sets provided by Genetic Analysis Workshop 12 were analyzed using a regression-based transmission/disequilibrium test that assesses linkage between a marker locus and quantitative trait locus when allelic association is present, as proposed by George et al. [Am J Hum Genet 65:236-45, 1999]. Because the same marker set and analytical technique was used, the results from these data sets are amenable for comparison. Statistically significant results common to both data sets were found on chromosomes 1 and 3. A noteworthy result, significant at p < 10(-4), was detected on chromosome 18 in the Hutterites.

Adult↗

PubMed2004

The clinical effectiveness of cognitive behaviour therapy: outcome for a large sample of adults treated in routine practice.

There is increasing interest in questions about how far the demonstrated efficacy of psychological therapies in research trials can be translated into clinical effectiveness in routine practice. This paper summarises outcome data from several hundred patients treated with CBT in routine clinical practice in a National Health Service psychology service, and compares their outcomes with some of the published research. Although the data have flaws common in ordinary clinical practice (no untreated controls, missing data, uncontrolled pharmacotherapy, etc.), the analyses suggest that CBT in this context is an effective treatment, albeit with probably not quite such good results as it achieves in research trials. Using clinical significance statistics on standardised measures, about half of the sample reliably improved over a course of therapy, including about a third who recovered to normal range.

Adolescent↗