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PubMed2002

Testing the relationship between morphological and molecular rates of change along phylogenies.

Molecular evolution has been considered to be essentially a stochastic process, little influenced by the pace of phenotypic change. This assumption was challenged by a study that demonstrated an association between rates of morphological and molecular change estimated for "total-evidence" phylogenies, a finding that led some researchers to challenge molecular date estimates of major evolutionary radiations. Here we show that Omland's (1997) result is probably due to methodological bias, particularly phylogenetic nonindependence, rather than being indicative of an underlying evolutionary phenomenon. We apply three new methods specifically designed to overcome phylogenetic bias to 13 published phylogenetic datasets for vertebrate taxa, each of which includes both morphological characters and DNA sequence data. We find no evidence of an association between rates of molecular and morphological rates of change.

Animals↗
PubMed2000

A new fast heuristic for computing the breakpoint phylogeny and experimental phylogenetic analyses of real and synthetic data.

The breakpoint phylogeny is an optimization problem proposed by Blanchette et al. for reconstructing evolutionary trees from gene order data. These same authors also developed and implemented BPAnalysis [3], a heuristic method (based upon solving many instances of the travelling salesman problem) for estimating the breakpoint phylogeny. We present a new heuristic for this purpose; although not polynomial-time, our heuristic is much faster in practice than BPAnalysis. We present and discuss the results of experimentation on synthetic datasets and on the flowering plant family Campanulaceae with three methods: our new method, BPAnalysis, and the neighbor-joining method [25] using several distance estimation techniques. Our preliminary results indicate that, on datasets with slow evolutionary rates and large numbers of genes in comparison with the number of taxa (genomes), all methods recover quite accurate reconstructions of the true evolutionary history (although BPAnalysis is too slow to be practical), but that on datasets where the rate of evolution is high relative to the number of genes, the accuracy of all three methods is poor.

Algorithms↗
PubMed1986

Genetic analysis workshop IV: insulin dependent diabetes mellitus--summary.

The Insulin Dependent Diabetes Mellitus (IDDM) study was one of the topics of Genetic Analysis Workshop IV (GAW IV) discussed October 7 - 8 at a pre-workshop meeting and presented October 9, 1985 at the American Society of Human Genetics meeting in Salt Lake City. The aim of the study was to have different groups analyze an identical body of real data in order to compare their analytical methods and the results based on their different approaches. This summary describes the available datasets and presents the main results of the nine participating groups. The detailed descriptions of analytical methods and results are presented in the individual papers following this overview. Although differing analytical methods were used there were no discrepancies regarding the interpretation of the data. Whereas the presented gametic associations were well established before, the real gain of this workshop was the unanimous result that the recessive 2-allele-model with incomplete penetrance had to be rejected and at least a 3-allele-model with differing susceptibility alleles and differing penetrances for heterozygotes and homozygotes had to be postulated for the transmission of IDDM.

Alleles↗
PubMed2006

Reducing multiclass cancer classification to binary by output coding and SVM.

Multiclass cancer classification based on microarray data is presented. The binary classifiers used combine support vector machines with a generalized output-coding scheme. Different coding strategies, decoding functions and feature selection methods are incorporated and validated on two cancer datasets: GCM and ALL. Using random coding strategy and recursive feature elimination, the testing accuracy achieved is as high as 83% on GCM data with 14 classes. Comparing with other classification methods, our method is superior in classificatory performance.

Artificial Intelligence↗
PubMed2000

Congenital Heart Surgery Nomenclature and Database Project: overview and minimum dataset.

The International Congenital Heart Surgery Nomenclature and Database Project was organized for the purpose of standardizing nomenclature and reporting strategies that would establish the foundations for an international database. Worldwide representatives met for a series of conferences, at which time, issues of nomenclature were discussed and debated. Authors were chosen to review the various congenital heart diagnoses and reflect the mediated debate that followed. Manuscripts were prepared that reviewed the appropriate extant nomenclature, made recommendations for an inclusive rather than an exclusive method of reporting, and determined a hierarchical database scheme that would allow several levels of reporting based on the data input. This manuscript outlines two datasets for an international congenital heart surgery database, a minimum dataset and a comprehensive dataset. The comprehensive dataset includes all the imagined variables, in a hierarchical scheme, which are detailed enough to generate risk stratification analyses. The minimum dataset will include data points that would create an essential dataset, which would be mandatory for data sharing and would lend itself to basic interpretation of trends. The minimum dataset has four drop-down menus for short lists of: (1) noncardiac abnormalities/general preoperative risk factors, (2) diagnoses, (3) procedures, and (4) complications, from which clinicians can choose for entry into the minimum dataset. There was universal agreement for these datasets and short lists by the assembled members of the Society of Thoracic Surgeons-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. The datasets and short lists were also unanimously approved by the Congenital Heart Surgery Committee of The European Association for Cardiothoracic Surgery and adopted by the European Congenital Heart Surgeons Foundation.

Databases, Factual↗
PubMed2004

Cumulative meta-analysis: a new tool for detection of temporal trends and publication bias in ecology.

Temporal changes in the magnitude of research findings have recently been recognized as a general phenomenon in ecology, and have been attributed to the delayed publication of non-significant results and disconfirming evidence. Here we introduce a method of cumulative meta-analysis which allows detection of both temporal trends and publication bias in the ecological literature. To illustrate the application of the method, we used two datasets from recently conducted meta-analyses of studies testing two plant defence theories. Our results revealed three phases in the evolution of the treatment effects. Early studies strongly supported the hypothesis tested, but the magnitude of the effect decreased considerably in later studies. In the latest studies, a trend towards an increase in effect size was observed. In one of the datasets, a cumulative meta-analysis revealed publication bias against studies reporting disconfirming evidence; such studies were published in journals with a lower impact factor compared to studies with results supporting the hypothesis tested. Correlation analysis revealed neither temporal trends nor evidence of publication bias in the datasets analysed. We thus suggest that cumulative meta-analysis should be used as a visual aid to detect temporal trends and publication bias in research findings in ecology in addition to the correlative approach.

Carbon↗
PubMed2006

The influence of the North Atlantic Oscillation on the sea-level around the northern European coasts reconsidered: the thermosteric effects.

The thermosteric contribution of the North Atlantic Oscillation (NAO) to the North Sea sea-level for the winter period is investigated. Satellite sea surface temperature as well as in situ measurements are used to define the sensitivity of winter water temperature to the NAO as well as to determine the trends in temperature. The sea surface temperature sensitivity to the NAO is about 0.85 degrees C per unit NAO, which results in thermosteric sea-level changes of about 1-2 cm per unit NAO. The sensitivity of sea surface temperatures to the NAO is strongly time-dependent. Model data from a two-dimensional hydrodynamic tide+surge model are used in combination with the estimated thermosteric anomalies to explain the observed sea-level changes and, in particular, the sensitivity of the datasets to the NAO variability. The agreement between the model and the observed data is improved by the inclusion of the thermosteric effect.

Atlantic Ocean↗
PubMed2006

Requirements for trainee logbooks.

All trainees are required to keep a logbook as a record of the procedures they have carried out during their surgical training. However, the current logbook is only a record of work carried out and not of the outcome of the operations. It does not prepare the trainee for either a lifetime practice of surgical audit or for a lifetime of learning from the audit process. The logbook requirements of different training boards vary and consequently, trainees find the keeping of a logbook an inconsistent process with ill-defined learning objectives. The Royal Australasian College of Surgeons should define what needs to be collected, how data should be verified and how experience and learning should be reported, and should approve electronic databases that meet logbook standards. The choice of database software and format can then be left to the trainee. Although there are good examples of electronic logbooks being developed, there is, at present, no perfect logbook available. We recommend that all trainees, from the commencement of basic surgical training, should keep a logbook that contains the minimum and expanded datasets in addition to specific trainee data on supervision and learning. In addition to the current reporting format focused on procedural casemix and supervision level, quality/outcome reports and a record of learning are recommended.

Clinical Competence↗
PubMed2000

Capture-recapture: a useful methodological tool for counting traffic related injuries?

INTRODUCTION: Although the capture-recapture technique is increasingly employed in studies of human populations to correct for under-ascertainment in traditional epidemiological surveillance, it has rarely been used in injury research. OBJECTIVES: To estimate the completeness of official data sources on traffic related injuries (TRIs) by using the capture-recapture technique and to calculate an ascertainment corrected number of fatal and serious TRIs among Scottish young people aged 15-24 years. The appropriateness of the approach in this context is also assessed. METHOD: A two sample capture-recapture technique was applied to two official sources of TRI data. Data on TRIs were obtained from the Scottish Health Service and the STATS19 dataset at the University of Essex Data Archive for 1995. Four standards (A-D) of matching were applied to fatalities and serious TRIs to allow plausible relaxation of matching standards within the context of the data collection setting. The completeness of each data source was assessed, and an ascertainment corrected number of fatalities and serious TRIs calculated. RESULTS: The ascertainment corrected number of TRI fatalities among 15-24 year olds using standard D was 104. This represents only a small increase in the number of fatalities using capture-recapture than when using each individual dataset. The completeness of the Scottish Health Service database for TRI fatalities was 93%. The STATS19 database was 95% complete. The ascertainment corrected number of TRI hospital admissions was 1969. The STATS19 and the Scottish Health Service databases were approximately two thirds and three quarters complete respectively for non-fatal TRIs requiring hospitalisation. CONCLUSIONS: Injury researchers have advocated the linkage of major datasets to supplement and improve the quality of injury data. Using capture-recapture we found that routine databases enumerate TRI fatalities accurately, in contrast to injury morbidity databases that do not. Capture-recapture is a potentially useful method of evaluating the completeness of data sources and identifying biases within datasets. However, ascertainment corrected rates should be viewed with caution. A number of requirements of the capture-recapture technique are unachieved in this study of injury in the human population.

Accidents, Traffic↗
PubMed2005

The effect of missing data on linkage disequilibrium mapping and haplotype association analysis in the GAW14 simulated datasets.

We used our newly developed linkage disequilibrium (LD) plotting software, JLIN, to plot linkage disequilibrium between pairs of single-nucleotide polymorphisms (SNPs) for three chromosomes of the Genetic Analysis Workshop 14 Aipotu simulated population to assess the effect of missing data on LD calculations. Our haplotype analysis program, SIMHAP, was used to assess the effect of missing data on haplotype-phenotype association. Genotype data was removed at random, at levels of 1%, 5%, and 10%, and the LD calculations and haplotype association results for these levels of missingness were compared to those for the complete dataset. It was concluded that ignoring individuals with missing data substantially affects the number of regions of LD detected which, in turn, could affect tagging SNPs chosen to generate haplotypes.

Chromosome Mapping↗
PubMed2000

The treatment of herpes simplex virus epithelial keratitis.

PURPOSE: Epithelial keratitis is the most common presentation of ocular infection by herpes simplex virus (HSV). Quantitative assessment of available therapy is needed to guide evidence-based ophthalmology. This study aimed to compare the efficacy of various treatments for dendritic or geographic HSV epithelial keratitis and to evaluate the role of various clinical characteristics on epithelial healing. METHODS: Following a systematic review of the literature, information from clinical trials of HSV dendritic or geographic epithelial keratitis was extracted, and the methodological quality of each study was scored. Methods of epithelial cauterization and curettage were grouped as relatively equivalent physicochemical therapy, and solution and ointment formulations of a given topical antiviral agent were combined. The proportion healed with 1 week of therapy, a scheduled follow-up day that approximated the average time of resolution with antiviral therapy, was selected as the primary outcome based on a masked evaluation of maximum treatment differences in published healing curves. The proportion healed at 14 days was recorded as supplemental information. Fixed-effects and random-effects meta-analysis models were used to obtain summary estimates by pooling results from comparative treatment trials. Hypotheses about which prognostic factors might affect epithelial healing during antiviral therapy were developed by multivariate analysis of the Herpetic Eye Disease Study dataset. RESULTS: After excluding 48 duplicate reports, 14 nonrandomized studies, 15 studies with outdated or similar treatments, and 29 trials lacking sufficient data on healing or accessibility, 76 primary reports were identified. These reports involved 4,251 patients allocated to 93 treatment comparisons of dendritic epithelial keratitis in 28 categories and 9 comparisons of geographic epithelial keratitis in 6 categories. For dendritic keratitis, idoxuridine was better than placebo at 7 days (combined odds ratio [OR], 3.59; 95% confidence interval [CI], 1.92-6.70), and at 14 days (OR, 4.17; 95% CI, 1.33-13.04), but pooling was limited by lack of homogeneity and low study quality. Direct comparisons at 1 week of treatment showed that trifluridine or acyclovir was significantly better than idoxuridine (OR, 3.12 and 4.56; 95% CI, 1.55-6.29 and 2.76-7.52, respectively), and indirect comparisons were also consistent with a clinically significant benefit. Vidarabine was not significantly better than idoxuridine in pooled treatment comparisons at 1 week (OR, 1.20; 95% CI, 0.72-2.00) but was better in 2 indirect comparisons (OR, 4.22 and 4.78; 95% CI, 1.69-10.54 and 2.15-10.65, respectively). At 14 days, trifluridine (OR, 6.05; 95% CI, 2.50-14.66), acyclovir (OR, 2.88; 95% CI, 1.39-4.78), and vidarabine (OR, 1.24; 95% CI, 0.65-2.37) were each better than idoxuridine. Trials of geographic epithelial keratitis also suggested that trifluridine, acyclovir, and vidarabine were more effective that idoxuridine. Other topical antiviral agents, such as bromovinyldeoxuridine, ganciclovir, and foscarnet, appeared equivalent to trifluridine or acyclovir. Oral acyclovir was equivalent to topical antiviral therapy and did not hasten healing when used in combination with topical treatment. Antiviral agents did not increase the speed of healing when compared to debridement but reduced the risk of recrudescent epithelial keratitis. The combination of physicochemical treatment with an antiviral agent seemed to be better than either physicochemical or antiviral treatment alone, but the heterogeneous cauterization and curettage techniques and the various treatment combinations limited valid quantitative summary effect measures. The combination of topical interferon with an antiviral agent was significantly better than antiviral therapy at 7 days (OR, 13.49; 95% CI, 7.39-24.61) but not at 14 days (OR, 2.36; 95% CI, 0.82-6.79). Finding apparent heterogeneity for some pooled estimates suggested that dissimilarities in patients, interventions, outcomes, or other logistical aspects of clinical trials occur across studies. CONCLUSIONS: The available evidence on the acute treatment of presumed HSV epithelial keratitis demonstrates the effectiveness of antiviral treatment and shows the log-logistic healing curve of treated dendritic epithelial keratitis. Topical trifluridine, acyclovir, and vidarabine were significantly more effective than idoxuridine but similar in relative effectiveness for dendritic epithelial keratitis. Physicochemical methods of removing infected corneal epithelium are effective, but adjunctive virucidal agents are needed to avert recrudescent epithelial keratitis. Whether debridement in combination with antiviral therapy is more beneficial than antiviral chemotherapy alone appears likely but remains inconclusive. The combination of topical interferon with an antiviral agent significantly speeds epithelial healing. Future trials of the acute treatment of HSV epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome and should consider the effect of lesion size and other characteristics on treatment response.

Administration, Topical↗
PubMed2006

Meta-analysis based on control of false discovery rate: combining yeast ChIP-chip datasets.

MOTIVATION: High-throughput microarray technology can be used to examine thousands of features, such as all the genes of an organism, and measure their expression. Two important issues of microarray bioinformatics are first, how to combine the significance values for each feature across experiments with high statistical power, and second, how to control the proportion of false positives. Existing methods address these issues separately, in spite of their linked usage. RESULTS: We present a novel method (ESP) to address the two requirements in an interdependent way. It generalizes the truncated product method of Zaykin et al. to combine only those significance values which clear their respective experiment-specific false discovery restrictive thresholds, thus allowing us to control the false discovery rate (FDR) for the final combined result. Further, we introduce several concepts that together offer FDR control, high power, quality control and speed-up in meta-analysis as done by our algorithm. Computational and statistical methods of research synthesis like the one described here will be increasingly important as additional genome-wide datasets accumulate in databases. We apply our method to combine three well-known ChIP-chip transcription factor binding datasets for budding yeast to identify significant intergenic regulatory sequences for nine cell cycle regulating transcription factors, both with high power and controlled FDR.

Algorithms↗
PubMed2006

Selecting normalization genes for small diagnostic microarrays.

BACKGROUND: Normalization of gene expression microarrays carrying thousands of genes is based on assumptions that do not hold for diagnostic microarrays carrying only few genes. Thus, applying standard microarray normalization strategies to diagnostic microarrays causes new normalization problems. RESULTS: In this paper we point out the differences of normalizing large microarrays and small diagnostic microarrays. We suggest to include additional normalization genes on the small diagnostic microarrays and propose two strategies for selecting them from genomewide microarray studies. The first is a data driven univariate selection of normalization genes. The second is multivariate and based on finding a balanced diagnostic signature. Finally, we compare both methods to standard normalization protocols known from large microarrays. CONCLUSION: Not including additional genes for normalization on small microarrays leads to a loss of diagnostic information. Using house keeping genes from the literature for normalization fails to work for certain datasets. While a data driven selection of additional normalization genes works well, the best results were obtained using a balanced signature.

Algorithms↗
PubMed2001

[Interactive health databases on the Internet].

In order to obtain reliable, comprehensive and current data, information systems which enable flexible presentation or analysis are necessary, as opposed to static tables. On-line and interactive numeric health databases on the Internet are increasingly available. Interactive tables can be produced in many fields, e.g., mortality, hospitalizations, cancer incidence, or motor vehicle accidents. The query screens are user-friendly and they can access remote, computerized data. Thus, it is possible to receive immediate responses to specific questions from national or international datasets, which can then be compared with local data--all without leaving one's chair. The aim of this review is to increase awareness of the existence of numeric health databases on the Internet, and their contribution to epidemiological research.

CD-ROM↗
PubMedDate not supplied

Fracture prediction for the femoral neck using finite element models.

Fracture of the femoral neck is an important clinical, social and economic topic. Prediction in subjects who are at risk for this type of fracture has been the object of numerous studies. Nonetheless, the methods of classification based on densitometric indicators alone have shown poor accuracy. It is the purpose of this study to propose a method to obtain an estimate of the resistance of the proximal femur, and to improve accuracy in prediction in subjects who are at risk for fracture. Based on the densitometric dataset alone, a bidimensional finite element model was developed that takes into account the distribution of density together with the femoral anatomy and the typical conditions of trauma. The model was applied to a group of preliminary osteoporotic patients. The statistical classification showed an increase in accuracy by 13%, as compared to a classification based on densitometric indicators alone.

Adult↗
PubMed2002

Error tolerant searching of uninterpreted tandem mass spectrometry data.

An error tolerant mode for database matching of uninterpreted tandem mass spectrometry data is described. Selected database entries are searched without enzyme specificity, using a comprehensive list of chemical and post-translational modifications, together with a residue substitution matrix. The modifications are tested serially, to avoid the catastrophic loss of discrimination that would occur if all the permutations of large numbers of modifications in combination were possible. The new mode has been coded as an extension to the Mascot search engine, and tested against a number of Liquid chromatography-tandem mass spectrometry datasets. The results show a number of additional peptide matches, but require careful interpretation. The most significant limitation of this approach is that it can only reveal new matches to proteins that already have at least one significant peptide match.

Animals↗
PubMed2006

Meta-analysis for microarray studies of the genetics of complex traits.

In comparison to other complex disease traits, alcoholism and alcohol abuse are influenced by the combined effects of many genes that alter susceptibility, phenotypic expression and associated morbidity, respectively. Many genetic studies, in both animal models and humans, have identified genetic intervals containing genes that influence alcoholism or behavioral responses to ethanol. Concurrently, a growing number of microarray studies have identified gene expression differences related to ethanol drinking or other ethanol behaviors. However, concerns about the statistical power of these experiments, combined with the complexity of the underlying phenotypes, have greatly hampered the identification of candidate genes underlying ethanol behaviors. Meta-analysis approaches using recent compilations of large datasets of microarray, behavioral and genetic data promise improved statistical power for detecting the genes or gene networks affecting ethanol behaviors and other complex traits.

Alcohol Drinking↗
PubMed2000

Multiple imputation compared with some informative dropout procedures in the estimation and comparison of rates of change in longitudinal clinical trials with dropouts.

Statistical analysis based on multiple imputation (MI) of missing data when analyzing data with missing observations is gaining popularity among statisticians because of availability of computing softwares; it might be tempting to use MI whenever data is missing. An important assumption behind MI is the "ignorability of missingness." In this paper, we demonstrate the use of MI in conjunction with random effects models and several other methods that are devised to handle nonignorable missingness (informative dropouts). We then compare the results to assess sensitivity to underlying assumptions. Our focus is primarily to estimate and compare rates of change (of a primary variable). The application dataset has a high dropout rate and has features to suggest informativeness of the dropout process. The estimates obtained under random effects modeling with multiple imputation were found to differ substantially from those obtained by methods devised to handle informative dropouts.

Algorithms↗