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PubMed2005

Reconstruction of ancient genome and gene order from complete microbial genome sequences.

Microbial genome sequences provide us with the fossil records for inferring their origination and evolution. Assuming that current microbial genomes are the evolutionary results of ancient genomes or fragments and the neighboring genes in ancient genomes are more likely neighbors in current genomes, in this paper we proposed a paleontological algorithm and assembled the orthologous gene groups from 66 complete and current microbial genome sequences into a pseudo-ancient genome, which consists of continuous fragments of various sizes. We performed bootstrap resampling and correlation analyses and the results showed that the assembled ancient genome and fragments are statistically significant and the genes of the same fragment are inherently related and likely derived from common ancestors. This method provides a new computational tool for studying microbial genome structure and evolution.

Algorithms↗

PubMed2004

Factors influencing survival in myelodysplastic syndromes in a Brazilian population: comparison of FAB and WHO classifications.

The WHO classification for myelodysplastic syndromes (MDS) has introduced new categories with prognostic relevance. Our aim was to examine the predictive value of the WHO and the FAB classification compared to parameters of peripheral blood, bone marrow and IPSS. Clinical data, peripheral blood counts, bone marrow (BM) cytology and histology and survival were analyzed in consecutive newly diagnosed adult patients with MDS. All cases were diagnosed according to FAB criteria and reclassified by the WHO proposal. Among 150 patients entering the study median age was 58 years (12-90). According to FAB, 90 patients had refractory anemia (RA), 18 sideroblastic anemia, 34 refractory anemia with excess of blasts (RAEB), three RAEB-t and five chronic myelomonocytic leukemia. Using the WHO proposal, one half of the patients with RA changed category. One patient had the 5q-syndrome. There were 25 cases with refractory cytopenias with multilineage dysplasia (RCMD) and 23 WHO "unclassified". These last patients presented few cell atypias, favorable IPSS and a good survival as has been described for refractory cytopenias in pediatric MDS. Hypocellular BM was found in 24% of the patients. Karyotype was available in only 85 cases. In the univariate analysis, both classifications, hemoglobin values, hypercellular bone marrow and IPSS had an influence on survival. Using the bootstrap resampling as stability test for the model created by the multivariate analysis, the WHO classification entered the model in 73%, FAB in 38% and IPSS in only 7%. Therefore, in a setting with a high number of low-risk MDS, the WHO classification is the best predictor of survival of the patients.

Adolescent↗

PubMed2004

The relationships of vigorous exercise, alcohol, and adiposity to low and high high-density lipoprotein-cholesterol levels.

While vigorous exercise, alcohol, and weight loss are all known to increase high-density lipoprotein-cholesterol (HDL-C), it is not known whether these interventions increase low HDL as effectively as has been demonstrated for normal HDL. This report tests the hypothesis that there may be differences in the calculated response of men and women with low versus high HDL-C to exercise, alcohol, and weight loss across the spectrum of HDL-C levels. Physican-supplied medical data from 7,288 men and 2,326 women were divided into deciles of self-reported vigorous exercise, alcohol intake, body mass index (BMI), or body circumferences. Within each decile we determined the percentiles of the HDL distributions and average running distance, alcohol intake, BMI, or body circumference. Simple least-squares regression analysis was then used to estimate the slope for kth HDL percentile (k = 5%, 6%, ...,95%) versus running distance, alcohol intake, BMI, or body circumference across deciles. Bootstrap resampling was used to estimate standard errors and statistical significance for the regression lines. In both sexes, the increase in HDL-C per unit alcohol intake was at least twice as great at the 95th as at the 5th percentile of the HDL distribution. There was also a significant graded increase from the 5th to the 95th HDL percentile for the slopes relating HDL to exercise (km run) and alcohol intake. Men's HDL-C declined in association with fatness (BMI, waist, and chest circumference) more sharply at the 95th than at the 5th percentile of the HDL distribution. The results of this study suggest that the effects of physical activity, alcohol, and weight reduction on HDL-C levels may be, to a large extent, dependent on the initial level with the greatest improvement achieved in subjects with high HDL and the least improvement in those having low HDL-C levels.

Adipose Tissue↗

PubMed2004

Spatiotemporal analysis of event-related fMRI data using partial least squares.

Partial least squares (PLS) has proven to be a important multivariate analytic tool for positron emission tomographic and, more recently, event-related potential (ERP) data. The application to ERP incorporates the ability to analyze space and time together, a feature that has obvious appeal for event-related functional magnetic resonance imaging (fMRI) data. This paper presents the extension of spatiotemporal PLS (ST-PLS) to fMRI, explaining the theoretical foundation and application to an fMRI study of auditory and visual perceptual memory. Analysis of activation effects with ST-PLS was compared with conventional univariate random effects analysis, showing general consensus for both methods, but several unique observations by ST-PLS, including enhanced statistical power. The application of ST-PLS for assessment of task-dependent brain-behavior relationships is also presented. Singular features of ST-PLS include (1) no assumptions about the shape of the hemodynamic response functions (HRFs); (2) robust statistical assessment at the image level through permutation tests; (3) protection against outlier influences at the voxel level through bootstrap resampling; (4) flexible analytic configurations that allow assessment of activation difference, brain-behavior relations, and functional connectivity. These features enable ST-PLS to act as an important complement to other multivariate and univariate approaches used in neuroimaging research.

Acoustic Stimulation↗

PubMed2004

Bootstrap white matter tractography (BOOT-TRAC).

White matter tractography is a noninvasive method for estimating and visualizing the white matter connectivity patterns in the human brain using diffusion tensor imaging (DTI) data. Sources of experimental noise may induce errors in the measured fiber directions, which will reduce the accuracy of the estimated white matter trajectories. In this study, a statistical nonparametric bootstrap method is described for estimating the dispersion and other errors in white matter tractography results. Prior studies have derived models of tractography error using the signal-to-noise ratio (SNR) and diffusion anisotropy of the DTI data. Tractography errors measured using bootstrap methods were generally consistent with an analytic model of tractography error except in areas where branching was evident. White matter tractography with bootstrap resampling is also applied to estimate the probabilities of connection between brain regions. The approach was used to generate probabilistic connectivity maps between the cerebral peduncles and specific cortical regions.

Brain↗

PubMed2005

Optimization of CD34+ collection for autologous transplantation using the evolution of peripheral blood cell counts after mobilization with chemotherapy and G-CSF.

BACKGROUND: Peripheral blood progenitor cells (PBPC) collection after high dose chemotherapy can be influenced by several factors. We searched for parameters that may predict the best day to start harvesting of PBPC in order to collect most CD34+ cells with the least number of aphereses. METHODS: We studied patients who underwent mobilization chemotherapy for autologous transplantation. The influence of age, sex, diagnosis, number of previous chemotherapy cycles, peripheral blood (PB) counts at day of mobilization (D0), day of neutrophils <1.0 x 10(9) l(-1) and day of nadir and interval between both (delta) on harvesting was investigated. Multivariate linear correlation models were built to predict the best harvesting with principles of parsimony. In patients where sequential CD34+ cell count was performed, the theoretical day of peak was calculated by interpolation in polynomial regression. RESULTS: One hundred and thirty four patients entered the analysis: 36 Hodgkin's lymphoma (HL), 65 B-large cell lymphoma (NHL) and 33 multiple myeloma (MM). Day of harvesting correlated with nr CHT, hemoglobin on D0, day of granulocytes <1.0 x 10(9) l(-1), delta and dosis of mobilization therapy. The day of CD34+ peak could be calculated by the formula = (-0.41) x Hemoglobin D0 + (day peripheral CD34+ cells = 10 x 10(6) microl(-1)) x 0.99 + 7.8. This model could explain 81% of the variance of the peak day and was stable by bootstrap resampling. Day of peripheral CD34+ cells = 10 x 10(6) microl(-1) preceded the calculated peak by 3-9 days. CONCLUSIONS: Although the day of best collection can be predicted using only sequential PB counts after mobilization chemotherapy, a model of prediction using peripheral CD34+ cell count is important especially for optimizing collection in poor mobilizing patients.

Adolescent↗

PubMed2004

Faecal egg count reduction test for assessing anthelmintic efficacy: average versus individually based estimations.

The faecal egg count reduction (FECR) in faeces is the most widely used method to assess the efficacy of anthelmintics against gastrointestinal strongyles. Several methods are used and they yield different efficacy values. They give important weight to those animals which excrete the majority of eggs, before or after treatment. We propose using individual animal FECR tests that give equal weight to every tested host. The first method is based on a before and after treatment without untreated controls, whereas the second one takes into account the use of non-treated control hosts. Confidence interval at P = 0.95 were established on bootstrap resamples for both individual-based methods. The individual-based FECR presented lower values than the average-based FECR in most cases. The individual FECR provided reliable evaluation when egg counts were over 300 eggs/g and when at least 10 animals were tested.

Animals↗

PubMed2004

Phylogeny and evolution of basils and allies (Ocimeae, Labiatae) based on three plastid DNA regions.

A phylogeny of basils and allies (Lamiaceae, tribe Ocimeae) based on sequences of the trnL intron, trnL-trnF intergene spacer and rps 16 intron of the plastid genome is presented. Several methods were used to reconstruct phylogenies and to assess statistical support for clades: maximum parsimony with equally and successively weighted characters, bootstrap resampling, and Bayesian inference. The phylogeny is used to investigate the distribution of morphological, pericarp anatomy, chemical, and pollen characters as well as the geographical distribution of the clades. Tribe Ocimeae is monophyletic and easily diagnosable with morphological synapomorphies. There are monophyletic clades within Ocimeae that broadly correspond to currently recognised subtribes: Lavandulinae, Hyptidinae, Ociminae, and Plectranthinae. Only Lavandulinae has clear non-molecular synapomorphies. Several currently recognised genera are not monophyletic. Floral morphology consistent with sternotribic pollination is most common in Ocimeae, but there are independent departures from this model. Buzz pollination is likely in some species, the only postulated occurrence of this within Lamiaceae. Quinone diterpenoids and flavones in the leaf exudates differ in their distributions across the phylogeny and this could contribute to differences in the recorded medicinal as well as pesticidal uses of the species in the different clades. Mapping geographic distribution on to an ultrametric phylogenetic tree produced using non-parametric rate smoothing supports an Asiatic origin for Ocimeae. There are several secondary occurrences in Asia arising from the African Ociminae and Plectranthinae clades. Colonisation of Madagascar occurred at least five times, and New World colonisation occurred at least three times.

Bayes Theorem↗

PubMed2004

Origin and diversification of the endemic Hawaiian tree snails (Achatinellidae: Achatinellinae) based on molecular evidence.

Tree snails of the endemic subfamily Achatinellinae comprise a diverse and important component of the Hawaiian fauna. In recent decades anthropogenic impacts have resulted in devastating extinction rates in Hawaiian tree snails. To address long-standing biogeographic, systematic, and evolutionary questions we used cytochrome c oxidase subunit I (COI) gene sequences to reconstruct the phylogeny of 23 extant species spanning the range of the subfamily from five Hawaiian Islands. To investigate family-level relationships, data were analyzed from 11 terrestrial pulmonate families. Although nodal support for monophyly of the endemic Pacific family Achatinellidae and endemic Hawaiian subfamily Achatinellinae was strong, bifurcation order among deeper ingroup nodes was not well-supported by bootstrap resampling. We hypothesize that lineage extinction and rapidity of lineage formation may have rendered evolutionary reconstruction difficult using a standard phylogenetic approach. Use of an optimized evolutionary model, however, improved resolution and recovered three main clades. The diversification pattern inferred contradicts the traditional biogeographic hypothesis of a Maui origin of the achatinelline lineage. Taxa comprising the basal ingroup clade (Achatinella spp.) and seeding lineages for subsequent clades originated on O'ahu. Therefore it appears that the ancestral colonizing species of achatinellines arrived first on O'ahu from an unknown source, and that O'ahu is the Hawaiian origin of the subfamily. Species previously defined by morphological criteria were generally found to be phylogenetically distinct, and the overall colonization pattern follows the island-age progression rule with several instances of generic polyphyly and back-colonization.

Animals↗

PubMed1999

A heuristic approach of maximum likelihood method for inferring phylogenetic tree and an application to the mammalian SOX-3 origin of the testis-determining gene SRY.

Applying the tree bisection and reconnection (TBR) algorithm, we have developed a heuristic method (maximum likelihood (ML)-TBR) for inferring the ML tree based on tree topology search. For initial trees from which iterative processes start in ML-TBR, two cases were considered: one is 100 neighbor-joining (NJ) trees based on the bootstrap resampling and the other is 100 randomly generated trees. The same ML tree was obtained in both cases. All different iterative processes started from 100 independent initial trees ultimately converged on one optimum tree with the largest log-likelihood value, suggesting that a limited number of initial trees will be quite enough in ML-TBR. This also suggests that the optimum tree corresponds to the global optimum in tree topology space and thus probably coincides with the ML tree inferred by intact ML analysis. This method has been applied to the inference of phylogenetic tree of the SOX family members. The mammalian testis-determining gene SRY is believed to have evolved from SOX-3, a member of the SOX family, based on several lines of evidence, including their sequence similarity, the location of SOX-3 on the X chromosome and some aspects of their expression. This model should be supported directly from the phylogenetic tree of the SOX family, but no evidence has been provided to date. A recently published NJ tree shows implausibly remote origin of SRY, suggesting that a more sophisticated method is required for understanding this problem. The ML tree inferred by the present method showed that the SRYs of marsupial and placental mammals form a monophyletic cluster which had diverged from the mammalian SOX-3 in the early evolution of mammals.

Algorithms↗

PubMed1992

The imprecision profile in immunoassay. A study using a resampling technique.

A resampling ('bootstrap') technique was applied to assess the reliability of the calculated imprecision profile (IP), as obtained from the dose/response curve and the response/error relationship (RER) using the cumulative data relative to two assays, i.e. a T4 radioimmunoassay (RIA) and a TSH immunofluorometric assay (IFMA), both run in duplicate. Mean values and the related uncertainty of the estimated dose errors were compared for different RER fitting conditions and different sizes of the duplicate response sets. The following observations were made: (a) compared to the maximum-likelihood procedure, the least-square fit proved to be unsuitable for estimating the parameters in the general RER equation variance(R) = aRb (where R indicates the response), (b) the simplifying assumption of a within-method constancy of the exponent in the RER equation, while acceptable for the T4 RIA, did not hold in the case of the TSH IFMA implying a much wider response range, (c) for both assays, response sets of ca. 100 duplicates were apparently compatible with an acceptable definition of the IP (+/- 10 to +/- 20% uncertainty).

Bias↗

PubMed2000

A clinical prediction rule for nerve-function impairment in leprosy patients.

BACKGROUND: Nerve-function impairment (NFI) commonly occurs during or after chemotherapy in leprosy and is the key pathological process leading to disability and handicap. We describe the development of a simple clinical prediction rule for estimating the risk of NFI occurrence. METHODS: New leprosy cases who presented to a centre in Bangladesh were recruited and followed up for 2 years in a field setting. We used multivariable regression analysis by Cox's proportional hazards model to identify predictive variables for NFI. Discriminative ability was measured by a concordance statistic. Internal validity was assessed with bootstrap resampling techniques. FINDINGS: 2510 patients were followed up for 2 years, 166 developed NFI. A simple model was developed with leprosy group (either paucibacillary leprosy [PB] or multibacillary leprosy [MB]) and the presence of any nerve-function loss at registration as predictive variables. Patients with PB leprosy and no nerve-function loss had a 1.3% (95% CI 0.8-1.8%) risk of developing NFI within 2 years of registration; patients with PB leprosy and nerve-function loss, or patients with MB leprosy and no nerve-function loss had a 16.0% (12-20%) risk; and patients with MB leprosy with nerve-function loss had a 65% (56-73%) risk. INTERPRETATION: Our prediction rule can be used to plan surveillance of new leprosy patients. Patients at low risk of NFI may need no follow-up beyond their course of chemotherapy (6 months); patients with intermediate risk need a minimum of 1 year of surveillance; and patients with high risk should have at least 2 years of surveillance for new NFI. Current recommendations for surveillance of patients with leprosy (for the duration of chemotherapy only) exclude an important group of patients who are at risk of developing NFI after completion of treatment.

Adolescent↗

PubMed1999

Smoothing bandwidth selection for response latency estimation.

Stimulus response latency is the delay between stimulus onset and the evoked modulation in neural activity. A common technique to estimate latencies involves binning the spike arrival times to form a peri-stimulus histogram. This histogram is smoothed using a fixed bandwidth. The estimated latency is the first time following stimulus onset in which the smoothed histogram exceeds the midpoint between the minimum and maximum of the smoothed histogram. We demonstrate that the choice of smoothing bandwidth is critical to the accuracy of this latency estimation technique. We suggest a bootstrap resampling technique for bandwidth selection which results in a robust latency estimate.

Animals↗

PubMed2003

Comparing the importance of prognostic factors in Cox and logistic regression using SAS.

Two SAS macro programs are presented that evaluate the relative importance of prognostic factors in the proportional hazards regression model and in the logistic regression model. The importance of a prognostic factor is quantified by the proportion of variation in the outcome attributable to this factor. For proportional hazards regression, the program %RELIMPCR uses the recently proposed measure V to calculate the proportion of explained variation (PEV). For the logistic model, the R(2) measure based on squared raw residuals is used by the program %RELIMPLR. Both programs are able to compute marginal and partial PEV, to compare PEVs of factors, of groups of factors, and even to compare PEVs of different models. The programs use a bootstrap resampling scheme to test differences of the PEVs of different factors. Confidence limits for P-values are provided. The programs further allow to base the computation of PEV on models with shrinked or bias-corrected parameter estimates. The SAS macros are freely available at www.akh-wien.ac.at/imc/biometrie/relimp

Data Interpretation, Statistical↗

PubMedDate not supplied

[Application of artificial neural networks for risk stratification of hospital mortality].

OBJECTIVE: To compare the ability of an artificial neural network (ANN) to predict hospital mortality with that of the Acute Physiology and Chronic Health Evaluation II (APACHE II) system and multiple logistic regression (LR). A secondary objective was to compare the allocation of individual probability among the models. METHOD: The variables required for calculating the APACHE II were prospectively collected. A total of 1146 patients were divided (randomly 70% and 30%) into the Development (800) and the Validation (346) sets. With the same variables an LR model and an ANN were carried out (a 3-layer perceptron trained by algorithm backpropagation with bootstrap resampling and with 9 nodes in the hidden layer) in the Development set. The models developed were contrasted with the Validation set and their discrimination properties were evaluated using the area under the ROC curve (AUC [95% CI]) and calibration with the Hosmer-Lemeshow C (HLC) test. Differences between the probabilities were evaluated using the Bland-Altman test. RESULTS: The Validation set showed an APACHE II with an AUC = 0.79 (0.75-0.84) and HLC = 11 (p = 0.329); LR model AUC = 0.81 (0.76-0.85) and HLC = 29 (p = 0.0001) and an ANN AUC = 0.82 (0.77-0.86) and HLC = 10 (p = 0.404). The patients with the most important differences in the allocation of probability between LR and ANN (8% of the total) were neurological. The worst results were found in trauma patients with an AUC of not greater than 0.75 in all the models. In respiratory patients, the ANN achieved the best AUC = 0.87 (0.78-0.91). CONCLUSIONS: The ANN was able to stratify hospital mortality risk by using the APACHE II system variables. The ANN tended to achieve better results than LR, since, in order to work, it does not require lineal restrictions or independent variables. Allocation of individual probability differed in each model.

Female↗

PubMed2003

Predictors of 6-month tobacco abstinence among 1224 cigarette smokers treated for nicotine dependence.

This study examined baseline characteristics associated with abstinence from tobacco 6 months after treatment for nicotine dependence. A total of 1224 cigarette smokers (619 females, 605 males) receiving clinical services for treatment of nicotine dependence between January 1, 1995 and June 30, 1997 were studied. The intervention involves a 45-min consultation with a nicotine dependence counselor. A treatment plan individualized to the patient's needs is then developed. The main outcome measure was the self-reported 7-day point prevalence abstinence from tobacco obtained by telephone interview 6-months after the consultation. A bootstrap resampling methodology for predictor variable selection was used to identify a set of multivariate predictors of 6-month tobacco abstinence. Five variables were multivariately associated with tobacco abstinence: male gender, no current psychiatric diagnosis, higher stage of change, longest duration of previous abstinence from tobacco of <1 or > or =30 days, and Fagerström Test for Nicotine Dependence (FTND) score of < or =5. Assessment of these variables may be useful clinically by assisting health care providers in tailoring nicotine dependence interventions to enhance outcomes.

Adolescent↗

PubMed1996

Event-related potential scalp fields during parallel and serial visual searches.

Event-related potential (ERP) scalp fields generated during parallel and serial searches were compared using a bootstrap resampling technique. Two different parallel search tasks required the detection of a single feature either color or orientation. A serial search task required the detection of the feature conjunction target: color and orientation. Identical stimuli were used for both parallel searches and a similar stimulus for the serial search. No evidence for scalp field differences earlier than 150 ms were discovered, suggesting that "low-level' visual processing is the same in both types of searches. ERP scalp fields that distinguished parallel from serial searches were identified between 150 and 250 ms. It is proposed that these different scalp fields represent timing and/or magnitude differences in the regions of cortex activated during parallel and serial searches.

Adult↗

PubMed2002

Statistical power and measurement allocation in ergonomic intervention studies assessing upper trapezius EMG amplitude. A case study of assembly work.

The present study aimed at exploring the statistical power of ergonomic intervention studies using electromyography (EMG) from the upper trapezius muscle. Data from a previous study of cyclic assembly work were reanalyzed with respect to exposure variability between subjects, between days, and within days. On basis of this information, the precision and power of different data collection strategies were explored. A sampling strategy comprising four registrations of about two min each (i.e. two work cycles) for one day per subject resulted in coefficients of variation between subjects on the 10-, 50-, and 90-APDF-percentiles of 0.44, 0.31, and 0.29, respectively. The corresponding necessary numbers of subjects in a study aiming at detecting a 20% exposure difference between two independent groups of equal size were 154, 78, and 68, respectively (p< or = 0.05, power 0.80). Multiple measurement days per subject would improve power, but only to a marginal extent beyond 4 days of recording. Increasing the number of recordings per day would have minor effects. Bootstrap resampling of the data set revealed that estimates of variability and power were associated with considerable uncertainty. The present results in combination with an overview of other occupational studies showed that common-size investigations using trapezius EMG percentiles are at great risk of suffering from insufficient statistical power, even if the expected intervention effect is substantial. The paper suggests a procedure of how to retrieve and use exposure variability information as an aid when studies are planned, and how to allocate measurements efficiently.

Data Interpretation, Statistical↗