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PubMed2005

Reduced oxidative stress in parallel to improved cardiac performance one year after selective removal of anti-beta 1-adrenoreceptor autoantibodies in patients with idiopathic dilated cardiomyopathy: data of a preliminary study.

Patients with idiopathic dilated cardiomyopathy (IDC) were treated with selective immunoadsorption to remove anti-beta 1-adrenoreceptor autoantibodies (anti-beta1A-AB). After one year, the effect on cardiac performance and oxidative stress was tested. Extracorporeal immunoadsorption of the whole IgG class in IDC patients for the removal of anti-beta1A-AB reduced oxidative stress in parallel to an improvement of cardiac performance. However, the non-specificity of IgG adsorption means that these beneficial effects cannot be attributed exclusively to anti-beta1A-AB removal. In an open clinical pilot study enrolling 8 patients with IDC prior to and one year after selective immunoadsorption of anti-beta1A-AB, plasma markers for oxidative stress--thiobarbituric acid-reactive substances (TBARS), lipid peroxides (LPO) and anti-oxidized low-density lipoprotein autoantibodies (anti-oxLDL-AB)--were measured in parallel to evaluation of the left ventricular function using conventional echocardiography and wall motion analysis by tissue Doppler imaging. After one year, TBARS (Wilcoxon test with bootstrapping simulation for paired data: 95% confidence interval of the P value 0.020 to 0.029) and anti-oxLDL-AB (P = 0.025 to 0.035) were decreased in parallel to an improvement of the peak systolic wall motion velocity (P = 0.006 to 0.01) and left ventricular ejection fraction (P = 0.002 to 0.02). For changes over the study period, a direct correlation with borderline significance (P = 0.076) was calculated for TBARS to the left ventricular diameter in the diastole. One year after selective immunoadsorption for anti-beta1A-AB removal, patients with ICD show a reduction in oxidative stress and a parallel improvement in cardiac performance.

Adsorption↗

PubMed2004

Performance of the Harris functional for extended basis sets at the Hartree-Fock and density functional levels.

The Harris functional is a noniterative variational procedure that uses an input charge density to produce an energy that is surprisingly accurate compared to the converged Kohn-Sham self-consistent result. We adapted and generalized this functional for the Hartree-Fock closed- and open-shell cases as well as examined its use for hybrid density functional methods such as B3LYP. Analysis of extended basis set calculations shows that at the B3LYP level an input density formed from a double zeta + polarization orbital basis is accurate enough to reproduce the energy of triple zeta + double polarization + diffuse orbital basis. For large molecules this translates into a computational speed that can be an order of magnitude faster. In the case of Hartree-Fock calculations a "bootstrapping technique" that employs successive applications of the Harris functional can further reduce computational times while retaining sufficient accuracy.

Journal Article↗

PubMed2003

Fossil sister group of craniates: predicted and found.

This study investigates whether the recently described Cambrian fossil Haikouella (and the very similar Yunnanozoon) throws light on the longstanding problem of the origin of craniates. In the first rigorous cladistic analysis of the relations of this animal, we took 40 anatomical characters from Haikouella and other taxa (hemichordates, tunicates, cephalochordates, conodont craniates and other craniates, plus protostomes as the outgroup) and subjected these characters to parsimony analysis. The characters included several previously unrecognized traits of Haikouella, such as upper lips resembling those of larval lampreys, the thick nature of the branchial bars, a mandibular branchial artery but no mandibular branchial bar, muscle fibers defining the myomeres, a dark fibrous sheath that defines the notochord, conclusive evidence for paired eyes, and a large hindbrain and diencephalon in the same positions as in the craniate brain. The cladistic analysis produced this tree: (protostomes, hemichordates (tunicates, (cephalochordates, (Haikouella, (conodonts + other craniates))))), with the "Haikouella + craniate" clade supported by bootstrap values that ranged from 81-96%, depending on how the analysis was structured. Thus, Haikouella is concluded to be the sister group of the craniates. Alternate hypotheses that unite Haikouella with hemichordates or cephalochordates, or consider it a basal deuterostome, received little or no support. Although it is the sister group of craniates, Haikouella is skull-less and lacks an ear, but it does have neural-crest derivatives in its branchial bars. Its craniate characters occur mostly in the head and pharynx; its widely spaced, robust branchial bars indicate it ventilated with branchiomeric muscles, not cilia. Despite its craniate mode of ventilation, Haikouella was not a predator but a suspension feeder, as shown by its cephalochordate-like endostyle, and tentacles forming a screen across the mouth. Haikouella was compared to pre-craniates predicted by recent models of craniate evolution and was found to fit these predictions closely. Specifically, it fits Northcutt and Gans' prediction that the change from ciliary to muscular ventilation preceded the change from suspension feeding to predatory feeding; it fits Butler's claim that vision was the first craniate sense to start elaborating; it is consistent with the ideas of Donoghue and others about the ancestor of conodont craniates; and, most strikingly, it resembles Mallatt's prediction of the external appearance of the ancestral craniate head. By contrast, Haikouella does not fit the widespread belief that ancestral craniates resembled hagfishes, because it has no special hagfish characters. Overall, Haikouella agrees so closely with recent predictions about pre-craniates that we conclude that the difficult problem of craniate origins is nearly solved.

Anatomy, Comparative↗

PubMed2006

Evidence at hand: Diversity, functional implications, and locomotor prediction in intrinsic hand proportions of diprotodontian marsupials.

Knowledge about the diversity, locomotor adaptations, and evolution of the marsupial forelimb is limited, resulting in an underrepresentation of marsupials in comparative anatomical literature on mammalian forelimb anatomy. This study investigated hand proportions in the diverse marsupial order Diprotodontia. Fifty-two measurements of 95 specimens representing 47 species, as well as 6 non-diprotodontian specimens, were explored using principal components analysis (PCA). Bootstrapping was used to assess the reliability of the loadings. Phylogenetically independent contrasts and phylogenetic ANOVA were used to test for correlation with size and functional adaptation of forelimbs for locomotor habit, scored as arboreal vs. terrestrial. Analysis of first principal component (PC1) scores revealed significant differences between arboreal and terrestrial species, and was related to relative slenderness of their phalangeal elements. Both locomotor groups displayed allometry along PC1 scores, but with different intercepts such that PC1 discriminated between the two locomotor habits almost completely. PC2 separated some higher-level clades and burrowing species. Analysis of locomotor predictors commonly applied by palaeontologists indicates that ratios between proximal and intermediate phalanges were unsuitable as predictors of arboreality/terrestriality, but the phalangeal index was more effective. From PCA results, a phalangeal slenderness ratio was developed which proved to be a useful discriminator, suggesting that a single unallocated phalanx can be used for an impression of locomotor mode in fossils. Most Diprotodontia are laterally paraxonic or ectaxonic, with the exception of digging species whose hands are medially paraxonic. Our results complement those of studies on placental mammals, suggesting that the demands of arboreality, terrestriality, or frequent digging on intrinsic hand proportions are met with similar anatomical adaptations in marsupials.

Adaptation, Physiological↗

PubMed2003

Genetic variation of varicella-zoster virus: evidence for geographical separation of strains.

Heteroduplex mobility assay was used to identify variants of varicella-zoster virus (VZV) circulating in the United Kingdom and elsewhere. Forty variable positions were identified. Sixteen substitutions were non-synonymous, resulting in an amino acid change, the majority of which were clustered within surface expressed proteins. Phylogenetic analysis distinguished at least three major clades (strains A, B, C) supported by significant bootstrap values. Apart from the United Kingdom and Brazil where all three strains were found, genotypes appeared to be closely associated with the geographical region in which they were sampled. Allelic co-segregation of widely spaced single nucleotide polymorphisms (SNPs) confirmed the genetic stability of the VZV. Recombination rates were difficult to calculate because of the low intra genotypic variation. However, one haplotype originating from Brazil is most parsimoniously explained as a recombinant between A and C strains, which co-occur in the region. Two further UK strains appeared to be recombinants between groups B and C.

Africa↗

PubMed2005

Genotype characterization and phylogenetic analysis of hepatitis B virus isolates from Iranian patients.

Hepatitis B virus (HBV) is one of the major causative agents of acute and chronic liver disease worldwide and is believed to be responsible for a million deaths annually. Eight genotypes of HBV, A to H, have been described on the basis of similarity of the complete genomes sequence. Although, it is reported that the predominant HBV genotype in the Mediterranean area and the middle east is genotype D, there are no reports on HBV genotypes prevalent in Iran. In this study, the C and S regions of HBV from 26 chronic hepatitis B Iranian patients were amplified and sequenced. Phylogenetic analysis revealed that all Iranian HBV isolates sequences were classified into genotype D with bootstrap values of 100%, 73%, and 100% (1,000 replicates each) for S, C, and preS2 regions, respectively. The mean percent intra-distance of S and C regions were 0.8% and 2.3%, respectively. The mean percent inter-distance of S and C regions between Iranians and genotype D isolates were 1.7% and 3.0%, respectively, and the range of mean percent nucleotide distance of S and C regions between Iranians and the other reference isolates were 7.9%-17.5% and 4.8%-14.7%, respectively. Thirteen out of 23 HBV C region sequences showed nucleotide "A" at position 1896 (precore mutant) in C region. Nucleotide 1858 showed presence of "T" in all isolates. No insertion or deletion was found in both regions. SimPlot and BootScanning analyses did not show any recombination between Iranian isolates and other genotypes in both regions.

Adult↗

PubMed2005

Complete genomic sequence and phylogenetic relatedness of hepatitis B virus isolates from Iran.

Hepatitis B virus (HBV) is one of the main etiological agents of acute and chronic liver disease that is still a major public health problem in the world. Numerous HBV isolates have grouped into eight genotypes, A to H, based on the complete genome sequence. To date, no study has been carried out on the complete HBV genome sequence in Iran. The objective of this study was to investigate the complete genome sequence organization and phylogenetic analysis of the five HBV strains, which obtained from Iranian chronic infected patients. Results showed that Iranian strains were closely related to each other, with 97-100% nucleotide similarity. Phylogenetic analysis based on the complete genome sequences and the precore/core gene sequences revealed that all strains were of genotype D, sub-genotype D1 with bootstrap value 100 and 99%, respectively. The S gene encoded Arg122, Pro127, and Lys160 corresponding to subtype ayw2. Iranian HBV isolates had closely related with Turkish HBV strains. All strains had a nucleotide length of 3,182 base pair (bp) except IR-P4 strain, with a 3,185 bp in length and with a unique Phe89 insertion in the X gene. The intragenotypic divergence of the complete genome sequence of Iranian strains was 1.8% and the intergenotypic in genotype D was 3.8% and with the other genotypes was 7.9-15.4%. In conclusion, this study revealed that the HBV genotype D, sub-genotype D1, subtype ayw2 dominates in the Iranian infected patients. A single Phe89 insertion in the X gene of the one Iranian strain with an unforeseen length of 3185 bp was identified.

Adult↗

PubMed2006

A previously unrecognized sixth genotype of GB virus C revealed by analysis of 5'-untranslated region sequences.

GB virus C (GBV-C) is a positive-strand RNA virus that infects a large proportion of the world's human population. It has been classified tentatively as a member of the Flaviviridae family and has been shown to exist as a group of five closely related genotypes. Recently, we reported the first full-length genome sequence of a genotype 5 isolate from South Africa. As part of the analysis of that sequence, a phylogenetic tree was elucidated from the 5'-untranslated region (UTR) that showed excellent congruence to the tree produced by analysis of complete open reading frame sequences. When 5'-UTR analysis was broadened subsequently to include additional isolates from around the globe, a heretofore unrecognized GBV-C genotype was discovered in Indonesia. When first reported in 2000, these isolates were described as constituting a novel fifth genotype. However, comparison to isolates from the then-known fourth and fifth genotypes (from Myanmar/Vietnam and South Africa, respectively) was not performed. A dataset of 121 GBV-C 5'-UTR sequences was complied and included representatives of the fourth and fifth genotypes as well as the "novel" Indonesian sequences and demonstrated, with strong support via bootstrap analysis, the existence of a sixth GBV-C genotype among infected individuals in Indonesia. The discovery of this sixth genotype emphasizes the diverse nature of GBV-C isolates and may have important implications for the interpretation of studies involving GBV-C/HIV co-infected individuals.

5' Untranslated Regions↗

PubMed2006

A variable region in the Crimean-Congo hemorrhagic fever virus L segment distinguishes between strains isolated from different geographic regions.

Alignment of Crimean-Congo hemorrhagic fever virus (CCHFV) L genome segment full-length sequences reveals an overall high level of conservation among strains, with greater than 90% of translated amino acid residues strictly conserved. However, a region of marked variability identified previously, corresponding to L polyprotein amino acid positions 760-810, shares only 40% overall identity between strains. The variable regions sequences of 16 laboratory-adapted CCHFV strains were determined, including 11 strains from European Russia, one strain from Bulgaria, and four strains from the Central Asian countries of Tajikistan, Turkmenistan, and Uzbekistan. Phylogenetic analysis demonstrates this L segment variable region sequence divides CCHFV strains into similar geographically-defined groupings observed for S segment-derived trees, but with higher bootstrap support and a much smaller character set required for analysis.

Africa↗

PubMed2006

Molecular epidemiology of hepatitis C virus subtype 3a in injecting drug users.

Hepatitis C virus subtype 3a (HCV-3a) originates from Asia and has spread widely among injecting drug users as well as other patient groups in industrialized countries. HCV subtype 3a infection remains highly prevalent and frequently transmitted in the population of intravenous drug users. The objective of this study was to understand better the mechanisms of the worldwide HCV-3a epidemics in drug users. Ninety-three sera from HCV-3a-infected IDUs from France, the United States, Brazil, Argentina, and Australia were studied. Phylogenetic analyses of the non-structural 5B region showed no specific clustering according to the continent of the patient's origin. Non-exclusive clusters of viral sequences from South America, Australia, and California were observed, but topologies were not supported by strong bootstrap values. The results suggest that HCV-3a has been transmitted from a common origin through a unique worldwide epidemic that rapidly spread among drug users. Regional transmission occurred in the recent past, leading to an embryonic genetic diversification of HCV-3a among local injecting drug user population.

Argentina↗

PubMed2002

Molecular changes associated with the transmission of avian influenza a H5N1 and H9N2 viruses to humans.

In order to identify molecular changes associated with the transmission of avian influenza A H5N1 and H9N2 viruses to humans, the internal genes from these viruses were compared to sequences from other avian and human influenza A isolates. Phylogenetically, each of the internal genes of all sixteen of the human H5N1 and both of the H9N2 isolates were closely related to one another and fell into a distinct clade separate from clades formed by the same genes of other avian and human viruses. All six internal genes were most closely related to those of avian isolates circulating in Asia, indicating that reassortment with human strains had not occurred for any of these 18 isolates. Amino acids previously identified as host-specific residues were predominantly avian in the human isolates although most of the proteins also contained residues observed previously only in sequences of human influenza viruses. For the majority of the nonglycoprotein genes, three distinct subgroups could be distinguished on bootstrap analyses of the nucleotide sequences, suggesting multiple introductions of avian virus strains capable of infecting humans. The shared nonglycoprotein gene constellations of the human H5N1 and H9N2 isolates and their detection in avian isolates only since 1997 when the first human infections were detected suggest that this particular gene combination may confer the ability to infect humans and cause disease. J. Med. Virol. 66:107-114, 2002. Published 2002 Wiley-Liss, Inc.

Animals↗

PubMed2004

Phylogenetic study on Shiraia bambusicola by rDNA sequence analyses.

In this study, 18S rDNA and ITS-5.8S rDNA regions of four Shiraia bambusicola isolates collected from different species of bamboos were amplified by PCR with universal primer pairs NS1/NS8 and ITS5/ITS4, respectively, and sequenced. Phylogenetic analyses were conducted on three selected datasets of rDNA sequences. Maximum parsimony, distance and maximum likelihood criteria were used to infer trees. Morphological characteristics were also observed. The positioning of Shiraia in the order Pleosporales was well supported by bootstrap, which agreed with the placement by Amano (1980) according to their morphology. We did not find significant inter-hostal differences among these four isolates from different species of bamboos. From the results of analyses and comparison of their rDNA sequences, we conclude that Shiraia should be classified into Pleosporales as Amano (1980) proposed and suggest that it might be positioned in the family Phaeosphaeriaceae.

Ascomycota↗

PubMed2006

A Process Analytical Technology approach to near-infrared process control of pharmaceutical powder blending: Part II: Qualitative near-infrared models for prediction of blend homogeneity.

The successful implementation of near-infrared spectroscopy (NIRS) in process control of powder blending requires constructing an inclusive spectral database that reflects the anticipated voluntary or involuntary changes in processing conditions, thereby minimizing bias in prediction of blending behavior. In this study, experimental design was utilized as an efficient way of generating blend experiments conducted under varying processing conditions such as humidity, blender speed and component concentration. NIR spectral data, collected from different blending experiments, was used to build qualitative models for prediction of blend homogeneity. Two pattern recognition algorithms: Soft Independent Modeling of Class Analogies (SIMCA) and Principal Component Modified Bootstrap Error-adjusted Single-sample Technique (PC-MBEST) were evaluated for qualitative analysis of NIR blending data. Optimization of NIR models, for the two algorithms, was achieved by proper selection of spectral processing, and training set samples. The models developed were successful in predicting blend homogeneity of independent blend samples under different processing conditions.

Algorithms↗

PubMed2006

Derivation of a risk index for the prediction of massive blood transfusion in liver transplantation.

Massive blood transfusion (MBT) remains a serious and common occurrence in liver transplantation surgery. This retrospective cohort study was undertaken to identify preoperative predictors of MBT and to develop a risk index for MBT in liver transplantation. Data were retrospectively collected on all liver transplantations carried out at a single institution between January 1998 and March 2004. Multivariable logistic regression analysis was used to identify independent predictor variables of MBT, defined as >/=6 units of red blood cell concentrate (RBC) in the first 24 hours of surgery. The model was internally validated by bootstrapping. Of the 460 liver transplant recipients, 193 (42%) received >/=6 units of RBC within 24 hours of surgery. Unadjusted analyses identified 12 preoperative predictors of MBT: age, height, gender, repeat transplantation, etiology of liver failure, and preoperative laboratory values (hemoglobin concentration, platelet count, international normalized ratio for prothrombin activity [INR], albumin, total bilirubin, and creatinine). In multivariable logistic regression, 7 independent predictors of MBT were identified: age (>40 years), hemoglobin concentration (</=10.0 g/dL), INR (1.2-1.99, and >2.0), platelet count (</=70 x 10(9)/L), creatinine (>/=110 micromol/L for female subjects and >/=120 micromol/L for male subjects), albumin (< 28 g/L), and repeat transplantation. The area under the receiver-operating characteristic curve (ROC) for the model was 0.82. By using the regression beta coefficients to derive weights for each of these predictors, a risk index was developed that assigned each patient a score between 0 and 8. The ROC for this risk index was 0.79. MBT in liver transplantation surgery can be accurately predicted by 7 readily available preoperative predictors.

Adult↗

PubMed2006

Real-time refinement of subthalamic nucleus targeting using Bayesian decision-making on the root mean square measure.

The subthalamic nucleus (STN) is a major target for treatment of advanced Parkinson's disease patients undergoing deep brain stimulation surgery. Microelectrode recording (MER) is used in many cases to identify the target nucleus. A real-time procedure for identifying the entry and exit points of the STN would improve the outcome of this targeting procedure. We used the normalized root mean square (NRMS) of a short (5 seconds) MER sampled signal and the estimated anatomical distance to target (EDT) as the basis for this procedure. Electrode tip location was defined intraoperatively by an expert neurophysiologist to be before, within, or after the STN. Data from 46 trajectories of 27 patients were used to calculate the Bayesian posterior probability of being in each of these locations, given RMS-EDT pair values. We tested our predictions on each trajectory using a bootstrapping technique, with the rest of the trajectories serving as a training set and found the error in predicting the STN entry to be (mean +/- SD) 0.18 +/- 0.84, and 0.50 +/- 0.59 mm for STN exit point, which yields a 0.30 +/- 0.28 mm deviation from the expert's target center. The simplicity and computational ease of RMS calculation, its spike sorting-independent nature and tolerance to electrode parameters of this Bayesian predictor, can lead directly to the development of a fully automated intraoperative physiological procedure for the refinement of imaging estimates of STN borders.

Bayes Theorem↗

PubMed2004

Use of resampling to select among alternative error structure specifications for GLMM analyses of repeated measurements.

Autocorrelated error and missing data due to dropouts have fostered interest in the flexible general linear mixed model (GLMM) procedures for analysis of data from controlled clinical trials. The user of these adaptable statistical tools must, however, choose among alternative structural models to represent the correlated repeated measurements. The fit of the error structure model specification is important for validity of tests for differences in patterns of treatment effects across time, particularly when maximum likelihood procedures are relied upon. Results can be affected significantly by the error specification that is selected, so a principled basis for selecting the specification is important. As no theoretical grounds are usually available to guide this decision, empirical criteria have been developed that focus on mode fit. The current report proposes alternative empirical criteria that focus on bootstrap estimates of actual type I error an power of tests for treatment effects. Results for model selection before and after the blind is broken are compared. Goodness-of-fit statistics also compare favourably for models fitted to the blinded or unblinded data, although the correspondence to actual type I error and power depends on the particular fit statistic that is considered.

Antidepressive Agents↗

PubMed2003

Determining and visualizing uncertainty in estimates of fiber orientation from diffusion tensor MRI.

Diffusion tensor MRI (DT-MRI) permits determination of the dominant orientation of structured tissue within an image voxel. This has led to the development of 2D graphical methods for representing fiber orientation and DT-MRI "tractography," which aims to reconstruct the 3D trajectories of white matter fasciculi. Most contemporary fiber orientation mapping schemes and tractography algorithms employ the directional information contained in the eigenvectors of the diffusion tensor to approximate white matter fiber orientation. However, while the uncertainty associated with every estimate of an eigenvector has long been recognized, no attempts to quantify this uncertainty in vivo have been reported. Here, a method is proposed for determining confidence intervals in fiber orientation from real DT-MRI data using the bootstrap method. This is used to construct maps of the "cone of uncertainty," allowing simultaneous viewing of fiber orientation and its uncertainty, and to examine the relationship between orientation uncertainty and tissue anisotropy.

Anisotropy↗

PubMed2004

Does fractional anisotropy have better noise immunity characteristics than relative anisotropy in diffusion tensor MRI? An analytical approach.

Fractional anisotropy (FA) and relative anisotropy (RA) are the two most commonly used scalar measures of anisotropy in diffusion tensor (DT) MRI. While a few published studies have shown that FA has superior noise immunity relative to RA, no theoretical basis has been proposed to explain this behavior. In the current study, the diffusion tensor invariants were used to derive a simple analytical expression that directly relates RA and FA. An analysis based on that analytical expression demonstrated that the FA images have a higher signal-to-noise ratio (SNR) than RA for any value of tensor anisotropy RA or FA > 0. This theoretical behavior was verified using both Monte Carlo simulations and bootstrap analysis of DT-MRI data acquired in a spherical water phantom and normal human subjects.

Anisotropy↗