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Genetic Diversity and Population Structure of Zambian Indigenous Cattle.

A study was conducted to determine the genetic diversity of Zambian indigenous cattle using microsatellites. In Zambia, cattle provide draft power, food, manure and generate income. DNA extraction followed the Qiagen protocol, and Arlequin V3.0 was used for data analysis. 72 unrelated animals from three regions, Eastern (Angoni), Southern (Tonga) and Western (Barotse), were sampled. 315 alleles observed were higher in TGLA 263 (106 bp) with 0.861, 0.824 and 0.753, BMS650 (160 bp) with 0.710 and SPS 115 (248 bp) with 0.581, 0.710 and 0.794 for Angoni, Tonga and Barotse, respectively. Effective allele frequency was 4.521 ± 0.351, 4.246 ± 0.299 and 3.888 ± 0.289 for Angoni, Tonga and Barotse, respectively. Global deficit of heterozygotes across populations (Fit) amounted to 4.2%. Overall mean deficit of heterozygotes (Fis = 1%), genetic differentiation among breeds (Fst = 3.2%),, and genetic flow between populations (Nm = 11.3) ranged from RM 067 (40.564) to BLI (3.016). Analysis of molecular variance revealed 2.7% genetic variation among populations and 97.3% within the cattle population, with a mean genetic diversity of 0.753. Structure analysis (PCoA) demonstrated the presence of two subpopulations in which all three populations are represented and these two groups showed evidence of substructuring. In the Bayesian analysis, Tonga and Barotse populations were clustered together, while the Angoni were separated from the rest of the populations in K = 2. There was no evidence of panmixia and linkage equilibrium; the VD (9.153) value is greater than L (5.929), indicating that the population was in equilibrium. This study presents a comprehensive genetic characterisation of indigenous cattle in Zambia, which is important for further studies.

Animals↗

Comparing bootstrap and posterior probability values in the four-taxon case.

Assessment of the reliability of a given phylogenetic hypothesis is an important step in phylogenetic analysis. Historically, the nonparametric bootstrap procedure has been the most frequently used method for assessing the support for specific phylogenetic relationships. The recent employment of Bayesian methods for phylogenetic inference problems has resulted in clade support being expressed in terms of posterior probabilities. We used simulated data and the four-taxon case to explore the relationship between nonparametric bootstrap values (as inferred by maximum likelihood) and posterior probabilities (as inferred by Bayesian analysis). The results suggest a complex association between the two measures. Three general regions of tree space can be identified: (1) the neutral zone, where differences between mean bootstrap and mean posterior probability values are not significant, (2) near the two-branch corner, and (3) deep in the two-branch corner. In the last two regions, significant differences occur between mean bootstrap and mean posterior probability values. Whether bootstrap or posterior probability values are higher depends on the data in support of alternative topologies. Examination of star topologies revealed that both bootstrap and posterior probability values differ significantly from theoretical expectations; in particular, there are more posterior probability values in the range 0.85-1 than expected by theory. Therefore, our results corroborate the findings of others that posterior probability values are excessively high. Our results also suggest that extrapolations from single topology branch-length studies are unlikely to provide any general conclusions regarding the relationship between bootstrap and posterior probability values.

Computer Simulation↗

The diagnosis of polyarteritis nodosa. I. A literature-based decision analysis approach.

We investigated diagnostic testing in polyarteritis nodosa (PAN) by calculating, from published data, the sensitivity and specificity of visceral angiography and muscle, nerve, testicle, kidney, and liver biopsy. Test sequence strategies were constructed by Bayesian inference using a computer program written for this purpose. Test sequences were compared with an aggressive strategy consisting of repeated tests until there was a positive finding or until the available tests were exhausted, and a conservative strategy consisting of 1 biopsy procedure plus angiography. The Bayesian analysis agreed most closely with the conservative approach for most prior probabilities (degree of suspicion) that a patient had PAN. The aggressive strategy had an overall sensitivity of 90% and specificity of 91%, whereas the conservative strategy was 85% sensitive and 96% specific. Furthermore, the aggressive strategy was more costly ($2,986 versus $1,961) and had a higher rate of morbidity (3.8 versus 2.7 days of hospitalization per patient evaluated) than did the conservative strategy. The mortality rates of both strategies were equivalent (approximately 0.05 deaths per hundred patients evaluated). The per-case cost of diagnosis increased as prevalence decreased, and at 10% prevalence, the aggressive strategy cost more than $17,000 per case diagnosed. Sensitivity analysis revealed that the strategies were moderately affected by the test characteristics, within reasonable assumptions, but that the differences in conservative and aggressive approaches remained. Thus, our analysis based on available data and the assumption of test independence suggests that the preferred diagnostic evaluation of patients with symptoms suggestive of PAN consists, in most cases, of a single biopsy procedure, with angiographic evaluation if necessary.

Costs and Cost Analysis↗

Molecular phylogeny of the carnivora (mammalia): assessing the impact of increased sampling on resolving enigmatic relationships.

This study analyzed 76 species of Carnivora using a concatenated sequence of 6243 bp from six genes (nuclear TR-i-I, TBG, and IRBP; mitochondrial ND2, CYTB, and 12S rRNA), representing the most comprehensive sampling yet undertaken for reconstructing the phylogeny of this clade. Maximum parsimony and Bayesian methods were remarkably congruent in topologies observed and in nodal support measures. We recovered all of the higher level carnivoran clades that had been robustly supported in previous analyses (by analyses of morphological and molecular data), including the monophyly of Caniformia, Feliformia, Arctoidea, Pinnipedia, Musteloidea, Procyonidae + Mustelidae sensu stricto, and a clade of (Hyaenidae + (Herpestidae + Malagasy carnivorans)). All of the traditional "families," with the exception of Viverridae and Mustelidae, were robustly supported as monophyletic groups. We further have determined the relative positions of the major lineages within the Caniformia, which previous studies could not resolve, including the first robust support for the phylogenetic position of marine carnivorans (Pinnipedia) within the Arctoidea (as the sister-group to musteloids [sensu lato], with ursids as their sister group). Within the pinnipeds, Odobenidae (walrus) was more closely allied with otariids (sea lions/fur seals) than with phocids ("true" seals). In addition, we recovered a monophyletic clade of skunks and stink badgers (Mephitidae) and resolved the topology of musteloid interrelationships as: Ailurus (Mephitidae (Procyonidae, Mustelidae [sensu stricto])). This pattern of interrelationships of living caniforms suggests a novel inference that large body size may have been the primitive condition for Arctoidea, with secondary size reduction evolving later in some musteloids. Within Mustelidae, Bayesian analyses are unambiguous in supporting otter monophyly (Lutrinae), and in both MP and Bayesian analyses Martes is paraphyletic with respect to Gulo and Eira, as has been observed in some previous molecular studies. Within Feliformia, we have confirmed that Nandinia is the outgroup to all other extant feliforms, and that the Malagasy Carnivora are a monophyletic clade closely allied with the mongooses (Herpestidae [sensu stricto]). Although the monophyly of each of the three major feliform clades (Viverridae sensu stricto, Felidae, and the clade of Hyaenidae + (Herpestidae + Malagasy carnivorans)) is robust in all of our analyses, the relative phylogenetic positions of these three lineages is not resolvable at present. Our analyses document the monophyly of the "social mongooses," strengthening evidence for a single origin of eusociality within the Herpestidae. For a single caniform node, the position of pinnipeds relative to Ursidae and Musteloidea, parsimony analyses of data for the entire Carnivora did not replicate the robust support observed for both parsimony and Bayesian analyses of the caniform ingroup alone. More detailed analyses and these results demonstrate that outgroup choice can have a considerable effect on the strength of support for a particular topology. Therefore, the use of exemplar taxa as proxies for entire clades with diverse evolutionary histories should be approached with caution. The Bayesian analysis likelihood functions generally were better able to reconstruct phylogenetic relationships (increased resolution and more robust support for various nodes) than parsimony analyses when incompletely sampled taxa were included. Bayesian analyses were not immune, however, to the effects of missing data; lower resolution and support in those analyses likely arise from non-overlap of gene sequence data among less well-sampled taxa. These issues are a concern for similar studies, in which different gene sequences are concatenated in an effort to increase resolving power.

Animals↗

Bayesian diagnosis in presence of pre-existing disease.

Clinicians are increasingly facing complex diagnostic problems in patients who have a pre-existing disease and in whom new symptoms develop which may be complications of that disease or manifestations of another, perhaps more common, condition. The neurological complications of malignancy fall into this situation. The results of diagnostic tests applied under these circumstances run the risk of being misinterpreted, largely due to lack of appreciation of the powerful effect of the pre-existing disease on a priori estimates of disease which enter the differential diagnosis. A bayesian analysis outlines the basic structure of these novel problems--a transient neurological disturbance in a man with lung cancer but a negative computerised tomographic scan illustrating the points. Bayesian probability revision yields accurate estimates of the predictive values of tests that tend to be different from those generated by intuitive clinical reasoning.

Bayes Theorem↗

Evolution of sugars in cider brandy aged in oak barrels: a contribution to its characterization.

A chemometric study was carried out to typify cider brandies according to the type of wood employed in the maturation process and their aging time. Monosaccharides, previously derivatized with p-aminobenzoic ethyl ester, were analyzed using a reversed-phase high-performance liquid chromatographic method. Univariate data treatment was not sufficient to enable differentiation of the classes of cider brandies on the basis of wood type and maturation time. Two linear combinations of original variables, ascertained by principal components analysis, provided an adequate data structurization. A mathematical decision rule was established to classify cider brandies with prediction capacities of 92 and 97% using an LDA method and Bayesian analysis, respectively. The use of the PLS algorithm allowed the authors to differentiate cider brandies according to the age and type of oak used in the aging process.

Alcoholic Beverages↗

Primate molecular divergence dates.

With genomic data, alignments can be assembled that greatly increase the number of informative sites for analysis of molecular divergence dates. Here, we present an estimate of the molecular divergence dates for all of the major primate groups. These date estimates are based on a Bayesian analysis of approximately 59.8 kbp of genomic data from 13 primates and 6 mammalian outgroups, using a range of paleontologically supported calibration estimates. Results support a Cretaceous last common ancestor of extant primates (approximately 77 mya), an Eocene divergence between platyrrhine and catarrhine primates (approximately 43 mya), an Oligocene origin of apes and Old World monkeys (approximately 31 mya), and an early Miocene (approximately 18 mya) divergence of Asian and African great apes. These dates are examined in the context of other molecular clock studies.

Animals↗

Molecular phylogenetic analysis places Percolomonas cosmopolitus within Heterolobosea: evolutionary implications.

Percolomonas cosmopolitus is a common free-living flagellate of uncertain phylogenetic position that was placed within the Heterolobosea on the basis of ultrastructure studies. To test the relationship between Percolomonas and Heterolobosea, we analysed the primary structure of the actin and small-subunit ribosomal RNA (SSU rRNA) genes of P. cosmopolitus as well as the predicted secondary structure of the SSU rRNA. Percolomonas shares common secondary structure patterns of the SSU rRNA with heterolobosean taxa, which, together with the results of actin gene analysis, confirms that it is closely related to Heterolobosea. Phylogenetic reconstructions based on the sequences of the SSU rRNA gene suggest Percolomonas belongs to the family Vahlkampfiidae. The first Bayesian analysis of a large taxon sampling of heterolobosean SSU rRNA genes clarifies the phylogenetic relationships within this group.

Animals↗

Response to cyclophosphamide, methotrexate, and fluorouracil in lymph node-positive breast cancer according to HER2 overexpression and other tumor biologic variables.

PURPOSE: There is considerable interest in biologic markers able to predict the response of cancer patients to therapy. HER2 overexpression is a potential indicator of responsiveness to doxorubicin and paclitaxel and of unresponsiveness to tamoxifen in breast carcinoma patients. However, the significance of HER2 overexpression in responsiveness to cyclophosphamide, methotrexate, and fluorouracil (CMF) has remained unclear. In this study, we investigated this issue in the 386 breast cancer patients in the first CMF controlled clinical trial with a 20-year follow-up. PATIENTS AND METHODS: Node-positive breast carcinoma patients were randomly assigned to receive either no further treatment after radical mastectomy (179 women) or 12 monthly cycles of adjuvant CMF chemotherapy (207 women). Overexpression of HER2 and the status of other tumor variables was assessed by immunohistochemistry in at least 324 (84%) of the 386 patients. Statistical analyses were performed to assess the efficacy of CMF treatment for the subgroups defined by HER2 and the status of other variables using a Bayesian approach. The end points considered were relapse-free survival (RFS) and cause-specific survival (CSS). RESULTS: Bayesian analysis of the treatment effect for HER2 and other variables indicated a clinical benefit from CMF treatment in all subgroups defined according to variables status. In particular regarding HER2 status, Bayesian estimates of RFS hazard ratios were equal to 0.484 and 0.641 and estimates of CSS hazard ratios were equal to 0.495 and 0.730 for HER2-positive and -negative tumors, respectively. CONCLUSION: CMF treatment showed a clinical benefit in the considered subgroups, defined according to HER2 and other tumor variables status. Patients with HER2-positive or HER2-negative tumors benefit from CMF treatment, and the poor prognosis associated with the HER2 overexpression in the untreated group could be completely overcome by the chemotherapy treatment.

Aged↗

Bayesian and information theory analysis of MAS sideband patterns in spin 1/2 systems.

Bayesian statistics and information theory are used to analyze the reliability of extracting chemical shift parameters from spinning sideband patterns of spin 1/2 systems. Efficient code has been written to calculate the two-dimensional posterior probability as a function of the chemical shift anisotropy, delta, and the asymmetry parameter, eta, given the sideband intensities and the signal-to-noise ratio. This method has the advantage of assuming only that the noise in the sideband intensities is distributed as a Gaussian. It assumes nothing about the distribution of the values of parameters delta and eta, which are shown in some cases to be highly non-Gaussian. The utility of Bayesian analysis is demonstrated on 1D slow-spinning MAS spectra and on sideband patterns extracted from 2D PASS spectra. Previous investigations have shown that there is an optimal range of spinning frequencies for determining delta. In this study, information theory is used to determine the signal-to-noise ratio dependence of the entropy in delta, eta, and total entropy in spinning sideband spectra. The entropy is a measure of the information content of a probability distribution. When the entropy is zero, there is perfect information on a system, while if it is infinite, there is no information on the system. It is found that for all values of eta and for signal-to-noise ratios in the range 50-1000, an entropy minimum in nudelta/nur occurs for values 1.5<or=nudelta/nur<or=3. In the same range of signal-to-noise ratios, the entropy in eta is a monotonically decreasing function of nudelta/nur. The global information content of a spinning sideband pattern (i.e., the total entropy) is dependent on the signal-to-noise ratio and has an optimal value at nudelta/nur approximately 2 at a signal-to-noise ratio of 50 and increasing to approximately 2.5 for signal-to-noise ratios of 1000. Finally, the increase of information in a sideband pattern as a function of the number of sidebands used in the analysis is examined. Most of the information about delta and eta is contained in the five central sidebands; i.e., sidebands -2 to 2.

Algorithms↗

Cladistic analysis of Bantu languages: a new tree based on combined lexical and grammatical data.

The phylogeny of the Bantu languages is reconstructed by application of the cladistic methodology to the combined lexical and grammatical data (87 languages, 144 characters). A maximum parsimony tree and Bayesian analysis supported some previously recognized clades, e.g., that of eastern and southern Bantu languages. Moreover, the results revealed that Bantu languages south and east of the equatorial forest are probably monophyletic. It suggests an unorthodox scenario of Bantu expansion including (after initial radiation in their homelands and neighboring territories) just a single passage through rainforest areas followed by a subsequent divergence into major clades. The likely localization of this divergence is in the area west of the Great Lakes. It conforms to the view that demographic expansion and dispersal throughout the dry-forests and savanna regions of subequatorial Africa was associated with the acquisition of new technologies (iron metallurgy and grain cultivation).

Africa↗

Standard and computed tomography in the evaluation of neoplasms of the chest. A comparative efficacy assessment.

Although in practice computed tomography (CT) has nearly replaced standard tomography in the evaluation of chest diseases, an analysis of the literature shows that standard tomography may be preferred in some settings. After a detailed review of studies on test performance, we calculated overall sensitivity and specificity values. Using Bayesian analysis, we then developed guidelines for choosing between computed and standard tomography. A test is recommended if its results might obviate the need for an invasive procedure. Standard tomography is recommended in the detection of mediastinal metastases from lung cancer. In the detection of hilar metastases, standard tomography is recommended for patients who have low pretest probabilities of metastases to this site, and computed tomography is recommended for patients who have high pretest probabilities. Computed tomography is recommended for the detection of calcification in solitary pulmonary nodules. Tomographic procedures are not recommended when the pretest probability is intermediate. The discrepancy between current practice and these guidelines highlights the need for carefully designed, multi-institutional comparative studies of radiographic procedures.

Humans↗

Estimation of error and bias in Bayesian Monte Carlo decision analysis using the bootstrap.

Bayesian Monte Carlo (BMC) decision analysis adopts a sampling procedure to estimate likelihoods and distributions of outcomes, and then uses that information to calculate the expected performance of alternative strategies, the value of information, and the value of including uncertainty. These decision analysis outputs are therefore subject to sample error. The standard error of each estimate and its bias, if any, can be estimated by the bootstrap procedure. The bootstrap operates by resampling (with replacement) from the original BMC sample, and redoing the decision analysis. Repeating this procedure yields a distribution of decision analysis outputs. The bootstrap approach to estimating the effect of sample error upon BMC analysis is illustrated with a simple value-of-information calculation along with an analysis of a proposed control structure for Lake Erie. The examples show that the outputs of BMC decision analysis can have high levels of sample error and bias.

Journal Article↗

18S ribosomal RNA gene sequences of Cochliopodium (Himatismenida) and the phylogeny of Amoebozoa.

Cochliopodium is a very distinctive genus of discoid amoebae covered by a dorsal tectum of carbohydrate microscales. Its phylogenetic position is unclear, since although sharing many features with naked "gymnamoebae", the tectum sets it apart. We sequenced 18S ribosomal RNA genes from three Cochliopodium species (minus, spiniferum and Cochliopodium sp., a new species resembling C. minutum). Phylogenetic analysis shows Cochliopodium as robustly holophyletic and within Amoebozoa, in full accord with morphological data. Cochliopodium is always one of the basal branches within Amoebozoa but its precise position is unstable. In Bayesian analysis it is sister to holophyletic Glycostylida, but distance trees mostly place it between Dermamoeba and a possibly artifactual long-branch cluster including Thecamoeba. These positions are poorly supported and basal amoebozoan branching ill-resolved, making it unclear whether Discosea (Glycostylida, Himatismenida, Dermamoebida) is holophyletic; however, Thecamoeba seems not specifically related to Dermamoeba. We also sequenced the small-subunit rRNA gene of Vannella persistens, which constantly grouped with other Vannella species, and two Hartmannella strains. Our trees suggest that Vexilliferidae, Variosea and Hartmannella are polyphyletic, confirming the existence of two very distinct Hartmannella clades: that comprising H. cantabrigiensis and another divergent species is sister to Glaeseria, whilst Hartmannella vermiformis branches more deeply.

Animals↗

Functional identification of an Arabidopsis pectin biosynthetic homogalacturonan galacturonosyltransferase.

Galacturonosyltransferases (GalATs) are required for the synthesis of pectin, a family of complex polysaccharides present in the cell walls of all land plants. We report the identification of a pectin GalAT (GAUT1) using peptide sequences obtained from Arabidopsis thaliana proteins partially purified for homogalacturonan (HG) alpha-1,4-GalAT activity. Transient expression of GAUT1 cDNA in the human embryonic kidney cell line HEK293 yielded uridine diphosphogalacturonic acid:GalAT activity. Polyclonal antibodies generated against GAUT1 immunoabsorbed HG alpha-1,4-GalAT activity from Arabidopsis solubilized membrane proteins. blast analysis of the Arabidopsis genome identified a family of 25 genes with high sequence similarity to GAUT1 and homologous genes in other dicots, in rice, and in Physcomitrella. Sequence alignment and phylogenetic Bayesian analysis of the Arabidopsis GAUT1-related gene family separates them into four related clades of GAUT and GAUT-like genes that are distinct from the other Arabidopsis members of glycosyltransferase family 8. The identification of GAUT1 as a HG GalAT and of the GAUT1-related gene family provides the genetic and biochemical tools required to study the function of these genes in pectin synthesis.

Arabidopsis↗

Genetic determination of individual birth weight and its association with sow productivity traits using Bayesian analyses.

Genetic association between individual birth weight (IBW) and litter birth weight (LBW) was analyzed on records of 14,950 individual pigs born alive between 1988 and 1994 at the pig breeding farm of the University of Kiel. Dams were from three purebred lines (German Landrace, German Edelschwein, and Large White) and their crosses. Phenotypically, preweaning mortality of pigs decreased substantially from 40% for pigs with < or = 1 kg weight to less than 7% for pigs with > 1.6 kg. For these low to high birth weight categories, preweaning growth (d 21 of age) and early postweaning growth (weaning to 25 kg) increased by more than 28 and 8% per day, respectively. Bayesian analysis was performed based on direct-maternal effects models for IBW and multiple-trait direct effects models for number of pigs born in total (NOBT) and alive (NOBA) and LBW. Bayesian posterior means for direct and maternal heritability and litter proportion of variance in IBW were .09, .26, and .18, respectively. After adjustment for NOBT, these changed to .08, .22, and .09, respectively. Adjustment for NOBT reduced the direct and maternal genetic correlation from -.41 to -.22. For these direct-maternal correlations, the 95% highest posterior density intervals were -.75 to -.07, and -.58 to .17 before and after adjustment for NOBT. Adjustment for NOBT was found to be necessary to obtain unbiased estimates of genetic effects for IBW. The relationship between IBW and NOBT, and thus the adjustment, was linear with a decrease in IBW of 44 g per additionally born pig. For litter traits, direct heritabilities were .10, .08, and .08 for NOBT, NOBA, and LBW, respectively. After adjustment of LBW for NOBA the heritability changed to .43. Expected variance components for LBW derived from estimates of IBW revealed that genetic and environmental covariances between full-sibs and variation in litter size resulted in the large deviation of maternal heritability for IBW and its equivalent estimate for LBW. These covariances among full-sibs could not be estimated if only LBW were recorded. Therefore, selection for increased IBW is recommended, with the opportunity to improve both direct and maternal genetic effects of birth weight of pigs and, thus, their vitality and pre- and postnatal growth.

Animals↗

Predictive model selection for repeated measures random effects models using Bayes factors.

The random effects model fit to repeated measures data is an extremely common model and data structure in current biostatistical practice. Modern data analysis often involves the selection of models within broad classes of prespecified models, but for models beyond the generalized linear model, few model-selection tools have been actively studied. In a Bayesian analysis, Bayes factors are the natural tool to use to explore these classes of models. In this paper, we develop a predictive approach for specifying the priors of a repeated measures random effects model with emphasis on selecting the fixed effects. The advantage of the predictive approach is that a single predictive specification is used to specify priors for all models considered. The methodology is applied to a pediatric pain data analysis.

Bayes Theorem↗

Genetic introgression between wild and stocked salmonids and the prospects for using molecular markers in population rehabilitation: the case of the Adriatic grayling (Thymallus thymallus L. 1785).

In the north Adriatic basin, a morphologically and genetically distinct lineage of grayling is found, designated as the Adriatic grayling. In Slovenia, the Adriatic grayling is restricted to the Soca river system, where it is critically endangered. The most pertinent threat is stocking with non-native, highly divergent Sava (Danubian) drainage stock, and this activity has been going on for more than four decades. The present study was designed to characterise the genetic structure of the Adriatic grayling in Slovenia, with particular emphasis on estimating the degree of introgression with non-indigenous stocked grayling. We analysed polymorphism at 154 microsatellite loci in samples representing grayling from the Adriatic and Danubian drainage stock. A relatively high number (12) of alleles, diagnostic for the Adriatic grayling, were identified. However, a correspondence analysis based on individual multilocus genotypes also revealed that there is no distinctive Adriatic group but rather a dispersed multitude of individuals that cannot be unambiguously distinguished from the more homogenous Danubian population. A Bayesian analysis of individual admixture coefficients confirmed this pattern and revealed extensive introgression between the Adriatic grayling and stocked grayling of Danubian origin. Average individual admixture coefficients showed that only between 50 and 60% of the original gene pools remained, and only few non-introgressed indigenous individuals could be identified. Microsatellite-based individual admixture analysis appear to be an important tool for identifying remaining non-introgressed indigenous individuals that could be used for restoring the original populations.

Alleles↗