SEARCH · PubMed Health

Results for “bootstrap”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources

PubMed2000

More taxa or more characters revisited: combining data from nuclear protein-encoding genes for phylogenetic analyses of Noctuoidea (Insecta: Lepidoptera).

A central question concerning data collection strategy for molecular phylogenies has been, is it better to increase the number of characters or the number of taxa sampled to improve the robustness of a phylogeny estimate? A recent simulation study concluded that increasing the number of taxa sampled is preferable to increasing the number of nucleotide characters, if taxa are chosen specifically to break up long branches. We explore this hypothesis by using empirical data from noctuoid moths, one of the largest superfamilies of insects. Separate studies of two nuclear genes, elongation factor-1 alpha (EF-1 alpha) and dopa decarboxylase (DDC), have yielded similar gene trees and high concordance with morphological groupings for 49 exemplar species. However, support levels were quite low for nodes deeper than the subfamily level. We tested the effects on phylogenetic signal of (1) increasing the taxon sampling by nearly 60%, to 77 species, and (2) combining data from the two genes in a single analysis. Surprisingly, the increased taxon sampling, although designed to break up long branches, generated greater disagreement between the two gene data sets and decreased support levels for deeper nodes. We appear to have inadvertently introduced new long branches, and breaking these up may require a yet larger taxon sample. Sampling additional characters (combining data) greatly increased the phylogenetic signal. To contrast the potential effect of combining data from independent genes with collection of the same total number of characters from a single gene, we simulated the latter by bootstrap augmentation of the single-gene data sets. Support levels for combined data were at least as high as those for the bootstrap-augmented data set for DDC and were much higher than those for the augmented EF-1 alpha data set. This supports the view that in obtaining additional sequence data to solve a refractory systematic problem, it is prudent to take them from an independent gene.

Animals↗

PubMed2002

A comparison of methods to handle skew distributed cost variables in the analysis of the resource consumption in schizophrenia treatment.

BACKGROUND: Transformation of the dependent cost variable is often used to solve the problems of heteroscedasticity and skewness in linear ordinary least square regression of health service cost data. However, transformation may cause difficulties in the interpretation of regression coefficients and the retransformation of predicted values. AIMS OF THE STUDY: The study compares the advantages and disadvantages of different methods to estimate regression based cost functions using data on the annual costs of schizophrenia treatment. METHODS: Annual costs of psychiatric service use and clinical and socio-demographic characteristics of the patients were assessed for a sample of 254 patients with a diagnosis of schizophrenia (ICD-10 F 20.0) living in Leipzig. The clinical characteristics of the participants were assessed by means of the BPRS 4.0, the GAF, and the CAN for service needs. Quality of life was measured by WHOQOL-BREF. A linear OLS regression model with non-parametric standard errors, a log-transformed OLS model and a generalized linear model with a log-link and a gamma distribution were used to estimate service costs. For the estimation of robust non-parametric standard errors, the variance estimator by White and a bootstrap estimator based on 2000 replications were employed. Models were evaluated by the comparison of the R2 and the root mean squared error (RMSE). RMSE of the log-transformed OLS model was computed with three different methods of bias-correction. The 95% confidence intervals for the differences between the RMSE were computed by means of bootstrapping. A split-sample-cross-validation procedure was used to forecast the costs for the one half of the sample on the basis of a regression equation computed for the other half of the sample. RESULTS: All three methods showed significant positive influences of psychiatric symptoms and met psychiatric service needs on service costs. Only the log- transformed OLS model showed a significant negative impact of age, and only the GLM shows a significant negative influences of employment status and partnership on costs. All three models provided a R2 of about.31. The Residuals of the linear OLS model revealed significant deviances from normality and homoscedasticity. The residuals of the log-transformed model are normally distributed but still heteroscedastic. The linear OLS model provided the lowest prediction error and the best forecast of the dependent cost variable. The log-transformed model provided the lowest RMSE if the heteroscedastic bias correction was used. The RMSE of the GLM with a log link and a gamma distribution was higher than those of the linear OLS model and the log-transformed OLS model. The difference between the RMSE of the linear OLS model and that of the log-transformed OLS model without bias correction was significant at the 95% level. As result of the cross-validation procedure, the linear OLS model provided the lowest RMSE followed by the log-transformed OLS model with a heteroscedastic bias correction. The GLM showed the weakest model fit again. None of the differences between the RMSE resulting form the cross- validation procedure were found to be significant. DISCUSSION: The comparison of the fit indices of the different regression models revealed that the linear OLS model provided a better fit than the log-transformed model and the GLM, but the differences between the models RMSE were not significant. Due to the small number of cases in the study the lack of significance does not sufficiently proof that the differences between the RSME for the different models are zero and the superiority of the linear OLS model can not be generalized. The lack of significant differences among the alternative estimators may reflect a lack of sample size adequate to detect important differences among the estimators employed. Further studies with larger case number are necessary to confirm the results. IMPLICATIONS: Specification of an adequate regression models requires a careful examination of the characteristics of the data. Estimation of standard errors and confidence intervals by nonparametric methods which are robust against deviations from the normal distribution and the homoscedasticity of residuals are suitable alternatives to the transformation of the skew distributed dependent variable. Further studies with more adequate case numbers are needed to confirm the results.

Adolescent↗

PubMed2003

Diagnosis of glaucoma by indirect classifiers.

OBJECTIVES: Demonstration of the applicability of a framework called indirect classification to the example of glaucoma classification. Indirect classification combines medical a priori knowledge and statistical classification methods. The method is compared to direct classification approaches with respect to the estimated misclassification error. METHODS: Indirect classification is applied using classification trees and the diagnosis of glaucoma. Misclassification errors are reduced by bootstrap aggregation. As direct classification methods linear discriminant analysis, classification trees and bootstrap aggregated classification trees are utilized in the problem of glaucoma diagnosis. Misclassification rates are estimated via 10-fold cross-validation. RESULTS: Indirect classification techniques reduce the misclassification error in the context of glaucoma classification compared to direct classification methods. CONCLUSIONS: Embedding a priori knowledge into statistical classification techniques can improve misclassification results. Indirect classification offers a framework to realize this combination.

Decision Support Techniques↗

PubMed2003

[Microsatellite analysis of genetic diversity and phylogenetic relationship of eight sheep breeds in Xinjiang].

To reveal the genetic diversity and syseighttemic relationship of main sheep breeds in north Xingjiang, the genetic polymorphisms of 10 microsatellites in 8 sheep breeds and one first filial generation (F1) in north Xinjiang were studied by means of PCR, polyacrylamide gel electrophoresis and silver staining. Number of alleles, average effective number of alleles (E) and average rates of homozygote of each breeds were counted. According to allele frequencies of ten microsatellites, polymorphism information content (PIC), mean heterozygosity (h) and genetic distances were calculated for each breeds. By using the Neighbor-joining method of Molecular Evolutionary Genetics Analysis software, a dendrogram was obtained based on genetic distances. Another dendrogram was obtained by Maximum Likelihood method in PHYLIP (3.6) software. The bootstrap values were evaluated for each crunode of the dendrogram by means of bootstrap test. The systemic relationship was analyzed as well. The results showed that 8 of 10 microsatellite loci were highly polymorphic, but BM1824 and MAF65 were low and medium polymorphic respectively, so the 8 microsatellite loci were effective markers for analysis of genetic relationship among sheep breeds. The average PIC (0.5631), h (0.5721) and E(2.9) of the whole population was all lower than those of other sheep breeds reported in the documents, which showed the gene polymorphisms and genetic diversity in these sheep breeds are relative rare. The genetic distances of native Aletai, Kazak and Bashibai sheeps in Xingjiang from foreign sheep breeds and cultivated breeds bearing foreign bloodline are relatively large. Consequently, they clustered in two groups. The phylogenetic relationship between different sheep breeds was in accordance with their resource, breeding history, differentiation and localities.

Algorithms↗

PubMed2003

[Analysis of genetic diversity of Shandong indigenous chicken breeds using microsatellite marker].

Microsatellite marker is one of the frequently used molecular markers. It has been used in the genotype identification, pedigree analysis and estimation of genetic distance. In this paper, five microsatellite markers with high polymorphisms were selected to detect the genetic diversity of seven chicken breeds. The alleles frequencies, polymorphism information content (PIC) and average heterozygosity within each population, and DA genetic distance among breeds were analyzed. The application of microsatellite polymorphisms to the detection of genetic variability and relationship among populations was discussed. Altogether, forty alleles were found in this experiment, and among them the most alleles (10) were detected by ADL0136 and the least (5) were detected by ADL0146. The distribution of alleles was not balanced, each locus having one or more dominant alleles. The average heterozygosity in the Shouguang chicken was the lowest (0.3327), and that in other breeds was also less than 0.4. It can be seen then that microsatellite polymorphisms can be used to reveal the variability within population through calculation of average heterozygosity. The PIC values ranged from 0.6169 (Shouguang chicken) to 0.7027 (Laiwu Black chicken). UPGMA tree was completed through analysis of DA genetic distance. In the tree, the Rizhao Pockmarked and the Jining Hundred chicken were first grouped together with a bootstrap value of 92%, before they were grouped with the Laiwu Black and the Shouguang chickens. The Anoka Yellow and the Guangxi Yellow chicken were grouped together with a bootstrap value of 80%, but the Luxi Fighting chicken had its own branch. In summary, the UPGMA tree well reflected the evolutionary and breeding history of the seven breeds.

Alleles↗

PubMed2003

Systematics of the lizard family pygopodidae with implications for the diversification of Australian temperate biotas.

We conducted a phylogenetic study of pygopodid lizards, a group of 38 species endemic to Australia and New Guinea, with two major goals: to reconstruct a taxonomically complete and robustly supported phylogeny for the group and to use this information to gain insights into the tempo, mode, and timing of the pygopodid radiation. Phylogenetic analyses of mitochondrial DNA (mtDNA), nuclear DNA (nDNA), and previously published morphological data using parsimony, maximum likelihood, and Bayesian methods on the independent and combined three data sets yielded trees with similar and largely stable ingroup topologies. However, relationships among the six most inclusive and unambiguously supported clades (Aprasia, Delma, Lialis, Ophidiocephalus, Pletholax, and Pygopus) varied depending on data set analyzed. We used parametric bootstrapping to help us understand which of the three-branch schemes linking these six taxa was most plausible given our data. We conclude based on our results that the arrangement ((((Delma, Lialis)Pygopus)Pletholax)(Aprasia, Ophidiocephalus)) represents the best hypothesis of intergeneric relationships. A second major problem to arise in our study concerned the inability of our two outgroup taxa (Diplodactylus) to root trees properly; three different rooting locations were suggested depending upon analysis. This long-branch attraction problem was so severe that the outgroup branch also interfered with estimation of ingroup relationships. We therefore used the molecular clock method to root the pygopodid tree. Results of two independent molecular clock analyses (mtDNA and nDNA) converged upon the same root location (branch leading to Delma). We are confident that we have found the correct root because the possibility of our clock estimates agreeing by chance alone is remote given that there are 65 possible root locations (branches) on the pygopodid tree (approximately 1 in 65 odds). Our analysis also indicated that Delma fraseri is not monophyletic, a result supported by a parametric bootstrapping test. We elevated the Western Australian race, Delma f. petersoni, to species status (i.e., Delma petersoni) because hybridization and incomplete lineage sorting could be ruled out as potential causes of this paraphyletic gene tree and because D. grayii is broadly sympatric with its sister species D. fraseri. Climate changes over the past 23 million years, which transformed Australia from a wet, green continent to one that is largely dry and brown, have been suspected as playing a major role in the diversification of Australia's temperate biotas. Our phylogenetic analyses of pygopodid speciation and biogeography revealed four important findings consistent with this climate change diversification model: (1) our fossil-calibrated phylogeny shows that although some extant pygopodid lineages predate the onset of aridification, 28 of 33 pygopodid species included in our study seem to have originated in the last 23 million years; (2) relative cladogenesis tests suggest that several major clades underwent higher than expected rates of speciation; (3) our findings support earlier studies showing that speciation of mesic-adapted biotas in the southeastern and southwestern corners of Australia largely occurred within each of these regions between 12 and 23 million years ago as opposed to repeated dispersal between these regions; and (4) we have identified for the first time the existence of several pairs of sympatric sister species of lizards living in arid and semiarid ecosystems. These sympatric sister species seem to be younger than allopatric or parapatric sister-species pairs, which is not consistent with previous beliefs.

Animals↗

PubMed2003

Least and most powerful phylogenetic tests to elucidate the origin of the seed plants in the presence of conflicting signals under misspecified models.

Several tests of molecular phylogenies have been proposed over the last decades, but most of them lead to strikingly different P-values. I propose that such discrepancies are principally due to different forms of null hypotheses. To support this hypothesis, two new tests are described. Both consider the composite null hypothesis that all the topologies are equidistant from the true but unknown topology. This composite hypothesis can either be reduced to the simple hypothesis at the least favorable distribution (frequentist significance test [FST]) or to the maximum likelihood topology (frequentist hypothesis test [FHT]). In both cases, the reduced null hypothesis is tested against each topology included in the analysis. The tests proposed have an information-theoretic justification, and the distribution of their test statistic is estimated by a nonparametric bootstrap, adjusting P-values for multiple comparisons. I applied the new tests to the reanalysis of two chloroplast genes, psaA and psbB, and compared the results with those of previously described tests. As expected, the FST and the FHT behaved approximately like the Shimodaira-Hasegawa test and the bootstrap, respectively. Although the tests give overconfidence in a wrong tree when an overly simple nucleotide substitution model is assumed, more complex models incorporating heterogeneity among codon positions resolve some conflicts. To further investigate the influence of the null hypothesis, a power study was conducted. Simulations showed that FST and the Shimodaira-Hasegawa test are the least powerful and FHT is the most powerful across the parameter space. Although the size of all the tests is affected by misspecification, the two new tests appear more robust against misspecification of the model of evolution and consistently supported the hypothesis that the Gnetales are nested within gymnosperms.

Bayes Theorem↗

PubMed2003

Novel versus unsupported clades: assessing the qualitative support for clades in MRP supertrees.

Matrix representation with parsimony (MRP) supertree construction has been criticized because the supertree may specify clades that are contradicted by every source tree contributing to it. Such unsupported clades may also occur using other supertree methods; however, their incidence is largely unknown. In this study, I investigated the frequency of unsupported clades in both simulated and empirical MRP supertrees. Here, I propose a new index, QS, to quantify the qualitative support for a supertree and its clades among the set of source trees. Results show that unsupported clades are very rare in MRP supertrees, occurring most often when there are few source trees that all possess the same set of taxa. However, even under these conditions the frequency of unsupported clades was <0.2%. Unsupported clades were absent from both the Carnivora and Lagomorpha supertrees, reflecting the use of large numbers of source trees for both. The proposed QS indices are correlated broadly with another measure of quantitative clade support (bootstrap frequencies, as derived from resampling of the MRP matrix) but appear to be more sensitive. More importantly, they sample at the level of the source trees and thus, unlike the bootstrap, are suitable for summarizing the support of MRP supertree clades.

Algorithms↗

PubMed2003

Overcoming confounded controls in the analysis of gene expression data from microarray experiments.

A potential limitation of data from microarray experiments exists when improper control samples are used. In cancer research, comparisons of tumour expression profiles to those from normal samples is challenging due to tissue heterogeneity (mixed cell populations). A specific example exists in a published colon cancer dataset, in which tissue heterogeneity was reported among the normal samples. In this paper, we show how to overcome or avoid the problem of using normal samples that do not derive from the same tissue of origin as the tumour. We advocate an exploratory unsupervised bootstrap analysis that can reveal unexpected and undesired, but strongly supported, clusters of samples that reflect tissue differences instead of tumour versus normal differences. All of the algorithms used in the analysis, including the maximum difference subset algorithm, unsupervised bootstrap analysis, pooled variance t-test for finding differentially expressed genes and the jackknife to reduce false positives, are incorporated into our online Gene Expression Data Analyzer ( http:// bioinformatics.upmc.edu/GE2/GEDA.html ).

Algorithms↗

PubMed2004

Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients.

OBJECTIVE: To assess the genotypic determinants of the virological response to tenofovir disoproxil fumarate (TDF) in a multicentre cohort of antiretroviral (ARV)-experienced patients receiving TDF as a part of a salvage therapy. METHODS: HIV-1 genotype was assessed at baseline in a subgroup of 161 patients of the French expanded access program receiving a stable TDF-including regimen for 3 months or more. Reverse transcriptase mutations associated with the viral load decrease at month 3 with a P-value <0.15 were retained for the construction of a mutation score. The score was then validated using a multivariate analysis and bootstrap resampling method. RESULTS: The strongest association with decrease in viral load was observed with a set of seven mutations (TDF mutation score) that consisted of M41L, E44D, D67N, T69D/N/S, L74V, L210W and T215Y/F RT mutations. The RT K65R mutation and the insertions at codon 69 were not included in the analysis due to low prevalences. A TDF mutation score of < or = 2 predicted the absence of resistance to TDF and > or = 6 mutations predicted resistance to TDF with corresponding reductions in viral load of -1.3 +/- 1.1, and +0.1 +/- 0.7 log10 copies/ml, respectively. In patients with a TDF mutation score of 3-5, the decrease in viral load was -0.8 +/- 1.0 log10 copies/ml and was considered possibly resistant. In the multivariate analysis, a TDF mutation score > or = 6, previous use of amprenavir, indinavir and lopinavir, and co-prescription of didanosine were associated with a worse virological response. The bootstrap analysis showed the robustness of the TDF mutation score. CONCLUSION: In ARV-experienced patients receiving TDF-containing regimens, a score derived from seven reverse transcriptase mutations was shown to be independently predictive of the virological response.

Adenine↗

PubMed2004

[Study on the calculation methods of confidence intervals of genetic parameter estimates by method R and number of repeating estimations].

The objective of the study was to probe the calculation methods of confidence intervals of genetic parameter estimates by Method R and influences of number of repeating estimations (NORE). Four models were used to generate the datasets by simulation. The datasets originated from 200 sires and 2 000 dams and simulation progressed by BLUP( Best Linear Unbiased Prediction) selection for five overlapping generations. Variance components were estimated by using multivariate multiplicative iteration (MMI), combined with preconditioned conjugate gradient (PCG) to solve the mixed model equations. Parameter estimates and their standard errors and confidence intervals were computed by classical method, classical method after Box-Cox transformation and bootstrapping. The results showed that when NORE was larger, all three methods were feasible, but when NORE was fewer, bootstrapping was recommended. Fewer NORE was feasible under simple models, but more NORE was needed for complex models. Direct heritabilities were overestimated with the increase of number of random effects, but underestimation was found for many parameters with the increase of iteration numbers of PCG and MMI.

Animals↗

PubMed2005

[Genomic structure of the autotetraploid oat species Avena macrostachya inferred from comparative analysis of the ITS1 and ITS2 sequences: on the oat karyotype evolution during the early stages of the Avena species divergence].

To examine the genomic structure of Avena macrostachya, internal transcribed spacers, ITS1 and ITS2, as well as nuclear 5.8S tRNA genes from three oat species with AsAs karyotype (A. wiestii, A. hirtula, and A. atlantica), and those from A. longiglumis (AlAl), A. canariensis (AcAc), A. ventricosa (CvCv), A. pilosa, and A. clauda (CpCp) were sequenced. All species of the genus Avena examined represented a monophyletic group (bootstrap index = 98), within which two branches, i.e., species with A- and C-genomes, were distinguished (bootstrap indices = 100). The subject of our study, A. macrostachya, albeit belonging to the phylogenetic branch of C-genome oat species (karyotype with submetacentic and subacrocentric chromosomes), has preserved an isobrachyal karyotype, (i.e., that containing metacentric chromosomes), probably typical of the common Avena ancestor. It was suggested to classify the A. macrostachya genome as a specific form of C-genome, Cm-genome. Among the species from other genera studied, Arrhenatherum elatius was found to be the closest to Avena in ITS1 and ITS structure. Phylogenetic relationships between Avena and Helictotrichon remain intriguingly uncertain. The HPR389153 sequence from H. pratense genome was closest to the ITS1 sequences specific to the Avena A-genomes (p-distance = 0.0237), while the differences of this sequence from the ITS1 of A. macrostachya reached 0.1221. On the other hand, HAD389117 from H. adsurgens was close to the ITS1 specific to Avena C-genomes (p-distance = 0.0189), while its differences from the A-genome specific ITS1 sequences reached 0.1221. It seems likely that the appearance of highly polyploid (2n = 12-21x) species of H. pratense and H. adsurgens could be associated with interspecific hybridization involving Mediterranean oat species carrying A- and C-genomes. A hypothesis on the pathways of Avena chromosomes evolution during the early stages the oat species divergence is proposed.

Avena↗

PubMed2005

Diabetes healthcare quality report cards: how accurate are the grades?

OBJECTIVE: To evaluate the accuracy and precision of random sampling in identifying healthcare system outliers in diabetes performance measures. STUDY DESIGN: Cross-sectional analysis of 79 Veterans Health Administration facilities serving 250 317 patients with diabetes mellitus between October 1, 1999, and September 30, 2000. METHODS: Primary outcome measures were poor glycosylated hemoglobin (A1C) control and good low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) control. Facility performance for each measure was calculated using 150 separate random samples and was compared with results using the bootstrap method as the criterion standard for determining outlier status (defined as a >/=5% difference from the mean, within the 10th or 90th percentile, or >/=2 SDs from the mean). RESULTS: The study population was largely male (97.4%), with 54.0% of subjects being 65 years or older. The facility-level mean performances were 22.8% for poor A1C control, 53.1% for good LDL-C control, and 55.3% for good BP control. Comparing the random sampling method with the bootstrap method, the sensitivity ranged between 0.64 and 0.83 for the 3 outcome measures, positive predictive values ranged between 0.55 and 0.88, and specificity and negative predictive values ranged between 0.88 and 0.99. CONCLUSIONS: The specificity and negative predictive value of the random sampling method in identifying nonoutliers in performance were generally high, while its sensitivity and positive predictive value were moderate. The use of random sampling to determine performance for individual outcome measures may be most appropriate for internal quality improvement rather than for public reporting.

Aged↗

PubMed2006

BayBoots: a model-free Bayesian tool to identify class markers from gene expression data.

One of the goals of gene expression experiments is the identification of differentially expressed genes among populations that could be used as markers. For this purpose, we implemented a model-free Bayesian approach in a user-friendly and freely available web-based tool called BayBoots. In spite of a common misunderstanding that Bayesian and model-free approaches are incompatible, we merged them in the BayBoots implementation using the Kernel density estimator and Rubin 's Bayesian Bootstrap. We used the Bayes error rate (BER) instead of the usual P values as an alternative statistical index to rank a class marker's discriminative potential, since it can be visualized by a simple graphical representation and has an intuitive interpretation. Subsequently, Bayesian Bootstrap was used to assess BER 's credibility. We tested BayBoots on microarray data to look for markers for Trypanosoma cruzi strains isolated from cardiac and asymptomatic patients. We found that the three most frequently used methods in microarray analysis: t-test, non-parametric Wilcoxon test and correlation methods, yielded several markers that were discarded by a time-consuming visual check. On the other hand, the BayBoots graphical output and ranking was able to automatically identify markers for which classification performance was consistent. BayBoots is available at: http://www.vision.ime.usp.br/~rvencio/BayBoots.

Animals↗

PubMedDate not supplied

[Neuropathic pain in Fabry's disease: heterogeneous remission in three years of enzyme replacement therapy].

INTRODUCTION: Fabry's disease is associated with acute neuropathic pain (NP). When six males with classic Fabry's disease ended three years of enzyme replacement therapy (ERT), studies were conducted to analyse the progression of the NP. PATIENTS AND METHODS: All of them received 1 mg/kg of agalsidase beta every 14 days. NP in hands and feet was evaluated at 0, 6, 12, 24 and 36 months, two modalities being considered: a) very intense pain or Fabry crises (FC), which forced the patient to rest, take analgesics and apply cold locally; b) acroparesthesias (AP), lower intensity itching, tingling and burning sensations that did not prevent them from continuing with their activities of daily living. The intensity of the FC (IFC) and the AP (IAP) were recorded using the Visual Analogue Scale, and the frequency with which both (FrFC and FrAP, respectively) appeared was measured in days. The one-tailed Wilcoxon test, binomial distribution and bootstrap method were used to carry out the analysis. RESULTS: After six months of ERT the IFC, IAP and FrCF remained the same, although the FrAP had become worse. As shown by the NP indexes that relate IFC/FrFC and IAP/FrAP, progress was therefore favourable. At one year, IFC continued, but FrFC and IAP were lower. At two years, the four NP measurements improved in five patients, although the FC and AP indexes did not vary in one patient. At three years, all the NP variables improved in the six patients. The slope representing NP as a function of time in all the bootstrap analyses was found to be p < 0.001. CONCLUSIONS: NP responded in a favourable, significant and heterogeneous manner and therefore justifies the early indication of ERT.

Adult↗

PubMed2006

Identification of protein biomarkers in Dupuytren's contracture using surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS).

BACKGROUND: To study the protein expression profiles associated with Dupuytren's contracture (DC) to identify potential disease protein biomarkers (PBM) using a proteomic technology--Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). METHODS: Normal and disease palmar fascia from DC patients were analyzed using Ciphergen's SELDI-TOF-MS Protein Biological System II (PBSII) ProteinChip reader. Analysis of the resulting SELDI-TOF spectra was carried out using the peak cluster analysis program (BioMarker Wizard, Ciphergen). Common peak clusters were then filtered using a bootstrap algorithm called SAM (Significant Analysis of Microarrays) for increased fidelity in our analysis. RESULTS: Several differentially expressed low molecular weight (<20 kDa) tissue proteins were identified. Spectra generated using both ZipTipC18 aided Au array and WCX2 array based SELDI-TOF-MS were reproducible, with an average peak cluster mass standard deviation for both methods of <1.74 x10(-4). Initial peak cluster analysis of the SELDI spectra identified both up-(14) and down-(3)regulated proteins associated with DC. Further analysis of the peak cluster data using the bootstrap algorithm SAM identified three disease-associated protein features (4600.8 Da, 10254.5 Da, and 11405.1 Da) that were elevated (5.45, 11.7, and 4.28 fold, respectively, with a 0% median false discovery rate). CONCLUSION: SELDI-TOF-MS identified three potential low molecular weight tissue protein markers (p4.6DC, p1ODC, p11.7DC) for DC. The ability of SELDI-TOF-MS to resolve low molecular weight proteins suggests that the method may provide a means of deciphering the biomarker-rich low molecular weight region of the human proteome. Application of such novel technology may help clinicians to focus on specific molecular abnormalities in diseases with no known molecular pathogenesis, and uncover therapeutic and/or diagnostic targets.

Algorithms↗

PubMed1988

Estimating the power of the two-sample Wilcoxon test for location shift.

Traditional methods for calculating the power of a statistical test for location shift require knowledge of the shape of the underlying probability distribution. The distribution shape, however, may be unknown. This paper describes a bootstrap method for using observed data (or pilot data) to approximate the power. No assumptions need be made about the shape of the underlying continuous probability distribution. Simulation evidence shows that, when applied to the Wilcoxon two-sample test for location shift, the suggested method is reliable. The evidence also shows that it is more accurate than a benchmark traditional approach. The bootstrap method is applied to a real-data example. The analysis demonstrates how the method can be used to determine sample sizes and how to choose the more powerful of two alternative tests for location shift.

Animals↗

PubMed1986

Alternative estimation procedures for Pr(X less than Y) in categorized data.

Consider two independent random variables X and Y. The functional R = Pr(X less than Y) [or gamma = Pr(X less than Y) - Pr(Y less than X)] is of practical importance in many situations, including clinical trials, genetics, and reliability. In this paper several approaches to estimation of gamma when X and Y are presented in discretized (categorical) form are analyzed and compared. Asymptotic formulas for the variances of the estimators are derived; use of the bootstrap to estimate variances is also discussed. Computer simulations indicate that the choice of the best estimator depends on the value of gamma, the underlying distribution, and the sparseness of the data. It is shown that the bootstrap provides a robust estimate of variance. Several examples are treated.

Analysis of Variance↗