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 667 records · Page 37Linked to original sources

PubMed2006

Methodological approach for assessing the cost-effectiveness of treatments using longitudinal observational data: the SOHO study.

OBJECTIVES: The objective of this study was to develop a method to allocate treatment effects when patients switch medication frequently in longitudinal observational studies and apply the approach to assess the cost-effectiveness of treatments in the Schizophrenia Outpatient Health Outcomes (SOHO) study. METHODS: Data were collected on patients at entry to the SOHO study at 3, 6, and 12 months. The 12-month follow-up period was considered as three epochs: 0-3 months, 3-6 months, and 6-12 months. Patients who switched treatment at 3 months had their new treatment considered as a new baseline observation, as these two 3-month observations provide two sets of information on the cost-effectiveness of a drug in the first 3 months after initiation. Multivariate regression analysis was used to adjust for baseline covariates. The model allowed for flexible functional forms, and the cost data were modeled using an exponential mean function. Bootstrapping assessed the uncertainty of the estimated parameters and incremental cost-effectiveness analysis decision rule. RESULTS AND CONCLUSIONS: We show the feasibility of the epoch analysis approach using data from the SOHO study comparing two antipsychotics. Estimates for the incremental cost and effectiveness per epoch over the full 12-month period are presented. Using the estimates of 200 bootstrap samples, we demonstrate how one drug is cost-effective compared with another.

Antipsychotic Agents↗

PubMed2004

Ecology and molecular characterization of dark septate fungi from roots, living stems, coarse and fine woody debris.

The aim of the present work was to determine the identity and molecular relationships between 127 strains of dark septate (DS) fungi isolated from healthy root tips, decayed coarse roots, live healthy-looking stems, coarse (stumps, snags and logs) and fine (tree branches and tops) woody debris in temperate-boreal forests in Sweden and Lithuania. Sequence analysis of ITS rDNA was used to identify the fungi. In a neighbour-joining similarity tree, all sequences were grouped into five distinct clusters. Within each of these, ITS rDNA sequence variation consisted of 2-18 nucleotides, corresponding to 1-3% of their total length. The four least variable clusters were supported with high bootstrap values of 86-100%. Comparisons with the sequences in the GenBank database showed that all our strains had a 95-100% homology with identified Phialocephala species, and they were thus assigned to this genus. The representatives of two clusters were identified, as P. fortinii and P. dimorphospora. The representatives of three remaining clusters were defined as Phialocephala sp. 35, Phialocephala sp. 6 and Phialocephala sp. 18. Within each of these clusters, ITS rDNA sequence uniformity was higher than that observed within P. fortinii and P. dimorphospora. Consequently, their clusters were most discrete, supported with bootstrap values of 100%. Genetic variation in the five distinguished Phialocephala species and their possible ecological roles are discussed. Phialocephala sp. 6 was confined to healthy root tips of conifers. P. dimorphospora was only associated with dead woody tissue of P. abies. P. fortinii, Phialocephala sp. 18 and sp. 35 were isolated from both dead and living conifers and Betula pendula. In conclusion, the present study revealed the ability of fungi from the genus Phialocephala to colonise and persist in live and dead trees under strikingly different ecological conditions.

Base Sequence↗

PubMed1999

Extending the p-plot: heuristics for multiple testing. HNRC group.

In the problem of large-scale multiple testing the p-plot is a graphically based competitor to the notoriously weak Bonferroni method. The p-plot is less stringent and more revealing in that it gives a gauge of how many hypotheses are decidedly false. The method is elucidated and extended here: the bootstrap reveals bias and sampling error in the usual point estimates, a bootstrap-based confidence interval for the gauge is given, as well as two acceptably powerful blanket tests of significance. Guidelines for use are given, and interpretational pitfalls pointed out, in the discussion of a case study linking premortem neuropsychological and postmortem neuropathologic data in an HIV cohort study.

Humans↗

PubMedDate not supplied

Prediction of properties from simulations: a re-examination with modern statistical methods.

We discuss models fit to data collected by Duffy and Jorgensen to predict solvation free energies and partition equilibria of drugs, organic molecules, aromatic heterocycles, and other molecules. These data were originally examined using linear regression, but here more recently developed statistical models are applied. The data set is complicated due to the presence of discrepant observations and also curvature in the response. In some cases it is possible to discard a small number of the observations to get good fit to the data, but, in others, discarding an increasing proportion of the observations does not improve the fit. Our general preference is to use robust parameter estimation which downweights to reduce the influence of discrepant observations on the fitted models. Models are selected for four responses using linear or more complicated representations of the explanatory variables, such as cubic polynomials, B-splines, or smoothers via generalized additive models (GAMs). Variables are chosen using the traditional approach of formal tests to assess contribution to the fit of a model, and resampling methods including bootstrap are also considered to assess the prediction error for given models. Results of our analysis indicate that GAMs are an improvement on linear models for describing the data and making predictions. In general robust regression models and GAMs have the smallest conditional expected loss of prediction over the four responses. In addition, robust regression models offer the advantage of identifying molecules that perform poorly in the fit. In general, models were identified that yielded an improvement of approximately 50% in the conditional expected loss of prediction compared with the original parametrization of Duffy and Jorgensen. It was also found that the use of cross-validation to compare models was unreliable, and bootstrapping is preferred.

Journal Article↗

PubMed2004

Modified polytopic vector analysis to identify and quantify a dioxin dechlorination signature in sediments. 2. Application to the Passaic River.

Persistent contaminants such as dioxins have been documented to undergo dechlorination reactions in the laboratory; however, little is known about the importance of these reactions in the field. Polytopic vector analysis (PVA) is a statistical pattern recognition technique for multivariate data traditionally used to identify fingerprints of contaminant sources. A modified PVA algorithm with uncertainty analysis was used to model dechlorination fingerprints and sources. The technique was applied to 351 sediment core-derived dioxin samples from the lower reach of the Passaic River, New Jersey. A dechlorination fingerprint was identified with a highly positive 2,3,7,8-tetraCDD component and a highly negative heptaCDD component. The most important industrial source of 2,3,7,8-tetraCDD is a fingerprint related to 2,4,5-trichlorophenoxyacetic acid production. The dechlorination contribution to the data variance is 3.00 +/- 1.00%, corresponding to an average of 1.2 microg/kg of 2,3,7,8-tetraCDD per sample at the expense of heptaCDD. The possible occurrence of dechlorination was validated by comparing the local dechlorination contribution in the results to the value of the ratio 2,3,7,8-tetraCDD/total 2,3,7,8-PCDD, which indicates dechlorination in the laboratory. Bootstrap uncertainty analysis yielded the same dechlorination EM in 40% of the realizations. The results indicated that bootstrapping is an important statistical tool to quantify uncertainties with respect to the dechlorination EM and some of the source EMs.

Algorithms↗

PubMed2002

An investigation of bone resorption and Dictyostelium discoideum growth inhibition by bisphosphonate drugs.

We report the results of 3D-QSAR/CoMFA investigations of the activity of bisphosphonate drugs, farnesyl pyrophosphate synthase (FPPSase) inhibitors, in the inhibition of bone resorption as well as the growth of Dictyostelium discoideum. In the case of D. discoideum, we find an experimental versus QSAR predicted pIC(50) R(2) value of 0.94 for 16 bisphosphonates over the 9-1200 microM range of IC(50) values, a cross-validated R(2) = 0.90, and a bootstrapped R(2) = 0.94, and we demonstrate that this approach has predictive utility (a 0.18 pIC(50) rms error for three test sets of 3 predictions). In bone resorption, we find an experimental versus predicted pLED (lowest effective dose) R(2) = 0.79 for 35 bisphosphonates over the 0.0001-1 mg of P/kg LED range, a cross-validated R(2) = 0.75, and a bootstrapped R(2) = 0.79. Two sets of 31 compounds were used as training sets for the predicted pLED values for two sets of 4 compounds which have an rms error of 0.44, larger than that found with D. discoideum. However, this can be attributed to the rather large uncertainties in the experimental bone resorption data which are almost all reported in decade steps (DeltapLED = 1). The CoMFA predicted (rat) bone antiresorptive pLED values are in agreement with literature (human recombinant) FPPSase inhibition results with an rms error of 0.45 (a factor of 2.8 error in activity prediction). We also report the single-crystal X-ray crystallographic structure of the compound most active in D. discoideum growth inhibition, 2-(3-picolyl)-aminomethylene-1,1-bisphosphonic acid. The structure clearly shows the presence of bond length alternation in the picolyl ring and a planar amino group linked by a very short (1.346 A) bond to the picolyl group, an amidinium-like structure which is also expected to occur in other highly active species such as minodronate and zoledronate. Overall, these results show that it is now possible to predict the activity of bisphosphonates using 3D-QSAR/CoMFA methods, although bone resorption studies should benefit from additional, accurate information on enzyme inhibition.

Alkyl and Aryl Transferases↗

PubMed1998

Resampling methods in sparse sampling situations in preclinical pharmacokinetic studies.

Toxicokinetic studies often require destructive sampling and the determination of drug concentrations in the various organs. Classically, the corresponding information is summarized in one mean concentration-time profile, which is regarded as representative for the animal population. On the basis of a mean profile, only estimates of the secondary pharmacokinetic parameters (for example AUC, t1/2) but no variability measures may be obtained. In this paper two resampling techniques are contrasted to Bailer's approach. The results obtained show that the resampling techniques can be considered a reliable alternative to Bailer's approach for the estimation of the standard error of the AUC t(k)0 in the case of normally distributed concentration data. They can be extended to the estimation of a variety of other secondary pharmacokinetic parameters and their respective standard deviations. One disadvantage with Bailer's method is its restriction to linear functions of the concentrations. On the other hand, using the population approach, prior knowledge of the underlying pharmacokinetic model is necessary. The resampling techniques discussed here, the "pseudoprofile-based bootstrap" (PpbB) and the "pooled data bootstrap" (PDB), are noncompartmental approaches. They are applicable under nonnormal data constellations and permit the estimation of the usual secondary pharmacokinetic parameters along with their standard deviations, standard errors, and other statistical measures. To assess the accuracy, precision, and robustness of the resampling estimators, theoretical data from three different pharmacokinetic models with different add-on errors (up to 100% variability) were analyzed. Even for the data sets with high variability, the parameters calculated with resampling techniques differ not more than 10% from the true values. Thus, in the case of data that are not normally distributed or when additional secondary pharmacokinetic parameters and their variability are to be estimated, the resampling methods are powerful tools in the safety assessment in preclinical pharmacokinetics and in toxicokinetics where generally sparse data situations are given.

Area Under Curve↗

PubMed2001

Identification and phylogeny of a non-specific endonuclease gene of white spot syndrome virus of shrimp.

White spot syndrome virus (WSSV) is a taxonomically unclassified virus which causes a disease in shrimps worldwide. A 936 bp long open reading frame (ORF) was found on a 7.2 kb HindIII fragment of the DNA genome of WSSV located adjacent to the ribonucleotide reductase small subunit gene. This putative ORF showed homology to prokaryotic and eukaryotic endonucleases, which contain a non-specific endonuclease motif. Alignment with viral and eukaryotic endonuclease ORFs revealed that most catalytically and structurally important amino acid residues were present in the putative WSSV non-specific endonuclease gene. An unrooted parsimonous phylogenetic tree of non-specific endonucleases indicated that the WSSV ORF was located in a well bootstrap supported clade containing only arthopods, including one of WSSV's natural hosts, Penaeus japonicus. A similar conjunction was found for the only other viral homologue, present in Fowlpox virus, which was also found in a well bootstrap-supported clade with its natural host, Gallus gallus. This clustering of virus and host suggests that both WSSV and Fowlpox virus may have acquired their nuclease genes from their respective natural hosts. Because the motif for non-specific nucleases is found in only two viruses, this gene cannot be used to clarify the taxonomic position of WSSV. However, the presence of this type of nuclease rarely found in viruses adds a novel feature to WSSV.

Amino Acid Motifs↗

PubMed2005

An alternative to Cohen's standardized mean difference effect size: a robust parameter and confidence interval in the two independent groups case.

The authors argue that a robust version of Cohen's effect size constructed by replacing population means with 20% trimmed means and the population standard deviation with the square root of a 20% Winsorized variance is a better measure of population separation than is Cohen's effect size. The authors investigated coverage probability for confidence intervals for the new effect size measure. The confidence intervals were constructed by using the noncentral t distribution and the percentile bootstrap. Over the range of distributions and effect sizes investigated in the study, coverage probability was better for the percentile bootstrap confidence interval.

Analysis of Variance↗

PubMed2005

Cost-effectiveness of a low-carbohydrate diet and a standard diet in severe obesity.

OBJECTIVE: Low-carbohydrate diets have become a popular alternative to standard diets for weight loss. Our aim was to compare the cost-effectiveness of these two diets. RESEARCH METHODS AND PROCEDURES: The patient population included 129 severely obese subjects (BMI = 42.9) from a randomized trial; participants had a high prevalence of diabetes or metabolic syndrome. We compared within-trial costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (CER) for the two study groups. We imputed missing values for QALYs. The CER was bootstrapped to derive 95% confidence intervals and to define acceptability cut-offs. We took a societal perspective for our analysis. RESULTS: Total costs during the one year of the trial were 6742 dollars +/- 6675 and 6249 dollars +/- 5100 for the low-carbohydrate and standard groups, respectively (p = 0.78). Participants experienced 0.64 +/- 0.02 and 0.61 +/- 0.02 QALYs during the one year of the study, respectively (p = 0.17 for difference). The point estimate of the incremental CER was -1225 dollars/QALY (i.e., the low-carbohydrate diet dominated the standard diet). However, in the bootstrap analysis, the wide spread of CERs caused the 95% confidence interval to be undefined. The probabilities that the low-carbohydrate diet was acceptable, using cut-offs of 50,000 dollars/QALY, 100,000 dollars/QALY, and 150,000 dollars/QALY, were 72.4% 78.6%, and 79.8%, respectively. DISCUSSION: The low-carbohydrate diet was not more cost-effective for weight loss than the standard diet in the patient population studied. Larger studies are needed to better assess the cost-effectiveness of dietary therapies for weight loss.

Adult↗

PubMed2002

Bump-hunting for the proficiency tester--searching for multimodality.

Kernel density estimation is a method for producing a smooth density approximation to a dataset and avoiding some of the problems associated with histograms. If it is used with a degree of smoothing determined by a fitness for purpose criterion, it can be applied to proficiency test data in order to test for multimodality in the z-scores. The bootstrap is an essential additional technique to determine how rugged the initially estimated kernel density is: the random resampling of the data in the bootstrap simulates a complete blind repeat of the proficiency test. In addition, useful estimates of the standard error of a mode can be thus obtained. It is suggested that a mode and its standard error can be used as an assigned value and its standard uncertainty.

Journal Article↗

PubMed2002

Soft-tissue anatomy of the extant hominoids: a review and phylogenetic analysis.

This paper reports the results of a literature search for information about the soft-tissue anatomy of the extant non-human hominoid genera, Pan, Gorilla, Pongo and Hylobates, together with the results of a phylogenetic analysis of these data plus comparable data for Homo. Information on the four extant non-human hominoid genera was located for 240 out of the 1783 soft-tissue structures listed in the Nomina Anatomica. Numerically these data are biased so that information about some systems (e.g. muscles) and some regions (e.g. the forelimb) are over-represented, whereas other systems and regions (e.g. the veins and the lymphatics of the vascular system, the head region) are either under-represented or not represented at all. Screening to ensure that the data were suitable for use in a phylogenetic analysis reduced the number of eligible soft-tissue structures to 171. These data, together with comparable data for modern humans, were converted into discontinuous character states suitable for phylogenetic analysis and then used to construct a taxon-by-character matrix. This matrix was used in two tests of the hypothesis that soft-tissue characters can be relied upon to reconstruct hominoid phylogenetic relationships. In the first, parsimony analysis was used to identify cladograms requiring the smallest number of character state changes. In the second, the phylogenetic bootstrap was used to determine the confidence intervals of the most parsimonious clades. The parsimony analysis yielded a single most parsimonious cladogram that matched the molecular cladogram. Similarly the bootstrap analysis yielded clades that were compatible with the molecular cladogram; a (Homo, Pan) clade was supported by 95% of the replicates, and a (Gorilla, Pan, Homo) clade by 96%. These are the first hominoid morphological data to provide statistically significant support for the clades favoured by the molecular evidence.

Anatomy, Comparative↗

PubMed2002

Phylogenetic relationships of Asian and European pig breeds determined by mitochondrial DNA D-loop sequence polymorphism.

Phylogenetic relationships among Asian and European pig breeds were assessed using 1036 bp of mitochondrial DNA (mtDNA) D-loop sequences. An unweighted pair-group method with arithmetic mean (UPGMA) tree was constructed on the basis of maximum likelihood distances using sequences determined for three Cheju (Korea), 11 Chinese, one Westran (Australian feral origin) and two European pigs (Berkshire and Welsh), and also published sequences for four Japanese (including two Wild Boars), one Yucatan miniature, five European (including Large White, Landrace, Duroc, Swedish and Wild Boar) and two Meishan pigs. The Colombian collared peccary (Tayassu tajacu) sequence was also determined and used as an outgroup. The maximum parsimony with heuristic search method was used to determine bootstrap support values. Asian-type pigs clustered together (bootstrap support 33%), but were separate from European-type pigs that also clustered together (93%). The Westran pig, derived from the feral descendants of pigs inhabiting Kangaroo Island of South Australia, clustered with Asian pigs, demonstrating Asian origin of their mitochondria. Berkshire and Large White clustered with Asian pigs, indicating that Asian pigs were involved in the development of these breeds. Our findings clearly demonstrate that pigs indigenous to China, Korea and Japan are only recently diverged from each other and distinctly different from European-type pigs. European pig breeds consist of pigs with mitochondria of Asian and non-Asian type, some of which were formed from closely related maternal ancestors, if not from a single ancestor.

Animals↗

PubMed2003

Population pharmacokinetics of platinum after nedaplatin administration and model validation in adult patients.

AIMS: The pharmacokinetics of unbound platinum after administration of an anticancer drug nedaplatin, cis-diammineglycolateplatinum were examined using population analysis. The relevant covariates and the extent of inter- and intra-individual variability were evaluated. METHODS: In order to clarify the pharmacokinetic profile of nedaplatin, unbound platinum concentrations (789 points) in plasma after intravenous infusion of nedaplatin were obtained from 183 courses for 141 patients. Plasma concentration data were analysed by nonlinear mixed effect modelling using NONMEM to evaluate the population mean parameters and variances for inter- and intra-individual random effects. The final population model was validated by parameter sensitivity analysis using objective function mapping, the bootstrap resampling and a data-splitting technique, i.e. the Jackknife method, and the predictive performance of the final model was evaluated. RESULTS: A two-compartment pharmacokinetic model with zero-order input and first order elimination described the current data well. The significant covariates were creatinine clearance (CLcr) for clearance of platinum (CL) [population mean [95% confidence interval (CI)] CL (l h(-1)) = 4.47 (3.27, 5.67) + 0.0738 (0.0581, 0.0896) x CLcr (CLcr: ml min(-1))] and body weight (BW: kg) for volume of distribution of platinum (Vc) [Vc (l) = 12.0 (7.5, 16.5) + 0.163 (0.081, 0.246) x BW]. Inter-individual variations (CV%, 95% CI) for CL and Vc were 25.5% (20.7, 29.6) and 21.4% (17.0, 24.1), respectively, and intra-individual variation (CV%, 95% CI) was 12.6% (10.5, 14.4). The effects of pretreatment with nedaplatin or other platinum agents on clearance and volume of distribution were also tested, but no significant effect was found. The relationship between the observed and predicted unbound platinum concentration by empirical Bayesian prediction showed good correlation with no bias, suggesting that the final model explains well the observed data in the patients. The mean prediction error and root mean square prediction error (95% CI) were - 0.0164 micro g ml(-1) (- 0.4379, 0.4051) and 0.2155 micro g ml(-1) (not calculable, 0.6523), respectively. The values of mean, standard error and 95% CI for objective function mapping, the bootstrap resampling, the Jackknife estimates and the final model coincided well. CONCLUSIONS: A population pharmacokinetic model was developed for unbound platinum after intravenous infusion of nedaplatin. Only creatinine clearance was found to be a significant covariate of clearance, and BW was found to be a significant covariate of volume of distribution. These population pharmacokinetic estimates are useful for setting initial dosing of nedaplatin using its population mean and can also be used for setting appropriate dosage regimens using empirical Bayesian forecasting.

Adult↗

PubMed2004

Morphological and genetic characteristics of Flavobacterium columnare isolates: correlations with virulence in fish.

Variability in pathogenicity of Flavobacterium columnare makes disease treatment difficult because there is currently no way to easily recognize those strains that warrant aggressive treatments. In order to identify suitable virulence markers, 17 isolates of F. columnare were cultured from six different fish species. The DNA from all isolates was analysed using random amplified polymorphic DNA (RAPD). Bootstrap analysis of the RAPD data produced a tree with three major groups supported by bootstrap scores of 80-100%. Virulence of the isolates was determined by bath exposure of channel catfish, Ictaluruspunctatus (Rafinesque), and golden shiners, Notemigonus crysoleucas (Mitchill), to broth cultures of F. columnare. In channel catfish, 13 of 17 isolates produced 100% mortality within 48 h post-exposure. All isolates of cyprinid fish origin clustered in a single RAPD group. At least two of the four isolates that were not virulent in channel catfish were of cyprinid fish origin. There was a wide variation in cell morphology between isolates with lengths of cells or cell chains ranging from 3 to 11 microm, even under identical culture conditions. Most of the shorter or single cell isolates fell into a single RAPD group. No clear association was identified between virulence and any other characteristic, including RAPD group.

Animals↗

PubMed2003

Simple estimation of the glomerular filtration rate in sick Thai children.

The objective of this study was to establish an appropriate formula for the estimation of creatinine clearance (CCr) in sick Thai children, and to evaluate the accuracy of using the Schwartz formula. Children aged between 0 and 19 years with various diseases and varying levels of renal function (but remained stable) were studied. Height in centimetres (L) and weight in kilograms (W), time of urine collection and urine volume were measured to provide urine flow (mL/min (V)) measurements. Body surface area (m2; SA) was also assessed. Quantitative urinary and plasma creatinine concentration (UCr and PCr, respectively) were determined. Creatinine clearance was calculated by using the following formula: UCr x V x 1.73/(PCr x SA). The linear association between CCr and L/PCr derived from these data was compared with the Schwartz formula by using bootstrap statistics. One-hundred and sixty children were studied. A least squares straight-line regression through the origin of CCr against L/PCr provided a good fit to the data. Our dataset revealed no evidence of an age or sex affect on the relationship. Creatinine clearance was estimated by using the following formula: 0.465 x (L/PCr), in which the calculated 95% confidence interval of the coefficient was 0.44-0.49. A comparison of this coefficient with that for the Schwartz formula for children aged > or =1 year (0.55), using 1000 bootstrapped resamples, showed an incompatibility between the two coefficients (P < 0.00005). In conclusion, we suggest estimating CCr in sick Thai children of either sex by using a modification of the Schwartz formula in which the coefficient equals 0.465.

Adolescent↗

PubMed2003

miLD and booLD programs for calculation and analysis of corrected linkage disequilibrium.

We describe software which calculates a set of linkage disequilibrium statistics, including multiallelic D' corrected by the bootstrap and permutation. The software also provides a tool for maximum likelihood and least squares estimation and testing of a set of hierarchical hypotheses formulated within the framework of the Malecot model of the decay of linkage disequilibrium with distance. Additionally, the bootstrap approach is used for estimation of the model parameter's confidence intervals and for hypothesis testing. The programs are available from http://www.geneticepi.com/Research/software/software.html

Algorithms↗

PubMed1994

Molecular phylogenetic studies on filarial parasites based on 5S ribosomal spacer sequences.

This paper is the first large-scale molecular phylogenetic study on filarial parasites (family Onchocercidae) which includes 16 species of 6 genera: Brugia beaveri Ash et Little, 1962, B. buckleyi Dissanaike et Paramananthan, 1961; B. malayi (Brug, 1927) Buckley, 1960; B. pahangi (Buckley et Edeson, 1956) Buckley, 1960; B. patei (Buckley, Nelson et Heisch, 1958) Buckley, 1960; B. timori Partono et al, 1977; Wuchereria bancrofti (Cobbold, 1877) Seurat, 1921: W. kalimantani Palmieri. Purnomo, Dennis and Marwoto, 1980: Mansonella perstans (Manson, 1891) Eberhard et Orihel, 1984; loa loc, Stiles, 1905; Onchocerca volvulus (Leuckart, 1983) Railliet er Henry, 1910; O. ochengi Bwangamoi, 1969; O. gutturosa Neumann, 1910; Dirofilaria immitis (Leidy, 1856) Railliet e Henry, 1911; Acanthocheilonema viteae (Krepkogorskaya, 1933) Bain, Baker et Chabaud, 1982 and Litomosoides sigmodontis Chandler, 1931. 5S rRNA gene spacer region sequence data were collected by PCR, cloning and dideoxy sequencing. The 5S rRNA gene spacer region sequences were aligned and analyzed by maximum parsimony algorithms, distance methods and maximum likelihood methods to construct phylogenetic trees. Bootstrap analysis was used to test the robustness of the different phylogenetic reconstructions. The data indicated that 5S spacer region sequences are highly conserved within species yet differ significantly between species. Spliced leader sequences were observed in all of the 5S rDNA spacers with no sequence variation, although flanking region sequence and length heterogeneity was observed even within species. All of the various tree-building methods gave very similar results. This study identified four clades which are strongly supported by bootstrap analysis the Brugia clade; the Wuchereria clade; the Brugia-Wuchereria clade and the Onchocerca clade. The analyses indicated that L. sigmodontis and A. viteae may be the most primitive among the 16 species studied. The data did not show any close relationship between Loa loa and D. immitis presently classified in the same subfamily, and the constitution of the Dirofilariinae subfamily is questionable.

Algorithms↗