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PubMed1994

Molecular phylogenetic studies on Brugia filariae using Hha I repeat sequences.

This paper is the first molecular phylogenetic study on Brugia parasites (family Onchocercidae) which includes 6 of the 10 species of this genus: B. beaveri Ash et Little, 1964; B. buckleyi Dissanaike et Paramananthan, 1961: B. malayi (Brug, 1927) Buckley, 1960; B. pahangi (Buckley et Edeson, 1956) Buckley, 1960; B. patei (Buckley, Nelson er Heisch, 1958) Buckley, 1960 and B. timori Partono et al., 1977. Hha l repeat sequences are 322 nucleotides long, highly repeated, tandemly arranged and unique to the nuclear genomes of the genus Brugia. Hha l repeat sequence data was collected by PCR, cloning and dideoxy sequencing. The Hha l repeat 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 the Hha l repeat sequences are highly conserved within species yet differ significantly between species. The various tree-building methods gave identical results. Bootstrap analyses on the Hha l repeat sequence data set identified at least two clades: the B. pahangi-B. beaveri clade and the B. malayi-B. timori-B. buckleyi clade; the first clade includes parasites of carnivores from Asia and America; the second includes species from primates and lagomorphs from Asiatic region. It was also noted that the Hha l repeat sequences obtained from B. malayi were identical to those obtained from B. timori, indicating very recent speciation.

Algorithms↗

PubMed2000

A phylogenetic analysis elucidating a case of patient-to-patient transmission of hepatitis C virus during surgery.

A phylogenetic hepatitis C virus (HCV) assay based on the core-Envelope 1 (C-E1) region was developed and used to elucidate a case of a patient-to-patient transmission. The index patient showed clinical symptoms of hepatitis seven weeks after surgery for hallux valgus under general anaesthesia. She progressed to a chronic persistent infection as indicated by positive HCV PCR results two years after surgery. Before her operation, a patient with HCV antibodies and positive HCV PCR had undergone surgery in the same room. There were two possibilities whereby the index patient could have been infected with hepatitis C, either through her work as a nurse or by transmission during surgery. By sequencing the 5' non-coding region PCR product, we found that both patients were infected with genotype 1a. Phylogenetic analysis with the variable C-E1 region suggested that the two patients clustered together with a bootstrap 100% in a tree with 75 sequence references. We further performed a phylogenetic analysis in this region with the genotype 1a reference sequences and an additional 25 genotype 1a sequences consecutively collected from Danish patients with HCV. The two patients still clustered together, supported by a high bootstrap 1000 value of 999. Homology analyses combined with the epidemiological findings indicate that the patient operated on in the same room before the index case was the most likely source of transmission. The mode of transmission could not be conclusively established, but a reusable part of the anaesthetic respiratory circuit is a possibility and a well known risk.

Adult↗

PubMed2001

Optimal electrocardiographic leads for detecting acute myocardial ischemia.

This study identifies the most sensitive electrocardiographic leads for monitoring ST-segment changes caused by acute coronary ischemia. The data set consisted of 120-lead electrocardiograms (ECGs) digitally recorded during balloon-inflation angioplasty in 3 groups of patients with single-vessel disease (left anterior descending [LAD], 32; right coronary artery [RCA], 36; left circumflex [LCx], 23). The ST deviation was measured in all recorded leads during baseline and ischemic states, and its difference between these 2 states (DeltaST) was calculated at 352 sites and plotted as DeltaST maps. The patients in each group were divided, by means of DeltaST criteria, into subgroups of "responders" and "nonresponders." Mean DeltaSTs for each group/subgroup were calculated and standardized by the corresponding standard deviation (SD); these values were plotted as mean DeltaST and t maps. Sites where extrema of DeltaST occurred most frequently were sought in bootstrap trials, performed in each group/subgroup. The results suggest that the optimal sites for the ischemia-sensitive leads are: V(3) (+) and just below V(8) (-) for LAD-related ischemia; the left iliac crest (+) and above V(3) at the third intercostal space (-) for RCA-related ischemia; and just below V(8) (+) and above V(2) at the third intercostal space (-) for LCx-related ischemia. Three "optimal" bipolar leads using these sites registered, in the responders from the LAD, RCA, and LCx groups, mean DeltaST (+/-SD) of 232 +/- 59, 245 +/- 96 and 158 +/- 91 microV, respectively; the corresponding t values were 15.14, 9.90, and 6.75. In the 12-lead ECG, only lead V(3) approached optimal DeltaST and t values for the LAD responders (187 +/- 61 microV; t = 11.75) and lead III for the RCA responders (191 +/- 76 microV; t = 9.73), but even these values were significantly suboptimal (P = 0.0011 and P = 0.0120, respectively). We found that the "optimal" bipolar leads can be derived, to an excellent approximation, from the 12 standard leads or from 3 EASI leads (with 3 electrodes at Frank's transverse level and 1 on the manubrium), by using precalculated regression coefficients. By means of bootstrap trials, we estimated the mean sensitivity (SE) and the mean positive predictive value (PPV) with which 3 "optimal" vessel-specific leads could identify ischemia related to the LAD, RCA, and LCx arteries, in the test set, as (SE/PPV) 94.7/92.8%, 78.7/80.9%, and 81.5/80.9%. A similar diagnostic performance can be achieved by vessel-specific leads derived from the 12-lead ECG (93.0/93.4%, 76.6/82.0%, and 82.7/77.1%) and, interestingly, from the EASI lead system (97.8/88.4%, 78.0/80.2%, and 76.8/83.2%). Thus, although the "optimal" bipolar leads for detecting ischemia related to each of the 3 coronary arteries were found to require sampling outside the 12-lead ECG, these leads can be derived from the full set of 12 standard leads or--for clinical monitoring applications--from the EASI lead system by using fewer electrodes at convenient locations.

Acute Disease↗

PubMed2006

[Decisions in case of "problematic" cost-effectiveness ratios based on the example of a clinical trial in rehabilitation care].

PURPOSE: Economic assessment of an additional psychological intervention in the rehabilitation of patients with chronic low-back pain and evaluation of results by decision makers. METHODS: Piggy-back cost-utility analysis of a randomised clinical trial, including a bootstrap analysis. Costs were measured by using the cost accounting systems of the rehabilitation clinics and by surveying patients. Health-related quality of life was measured using the EQ-5D. Implications of different representations of the decision problem and corresponding decision rules concerning the cost-effectiveness plane are discussed. RESULTS: As compared with the 126 patients of the control arm, the 98 patients in the intervention arm gained 3.5 days in perfect health on average as well as 1219 euro cost saving. However, because of the uncertainty involved, the results of a bootstrap analysis cover all quadrants of the cost-effectiveness plane. Using maximum willingness-to-pay per effect unit gained, decision rules can be defined for parts of the cost-effectiveness plane. These have to be aggregated in a further valuation step. CONCLUSIONS: Study results show that decisions on stochastic economic evaluation results may require an additional valuation step aggregating the various parts of the cost-effectiveness plane.

Cost-Benefit Analysis↗

PubMed2003

A comparison of on-pump and off-pump coronary bypass surgery in low-risk patients.

BACKGROUND: The performance of coronary bypass surgery without cardiopulmonary bypass ("off pump") may reduce perioperative morbidity and costs, but it is uncertain whether the outcome is similar to that involving the use of cardiopulmonary bypass ("on pump"). METHODS: In a multicenter, randomized trial, we randomly assigned 139 patients with predominantly single- or double-vessel coronary disease to on-pump surgery and 142 to off-pump surgery. Cardiac outcome and cost effectiveness were determined one year after surgery. The uncertainty surrounding the cost-effectiveness ratio (cost differences per quality-adjusted year of life gained) was addressed by bootstrapping. RESULTS: At one year, the rate of freedom from death, stroke, myocardial infarction, and coronary reintervention was 90.6 percent after on-pump surgery and 88.0 percent after off-pump surgery (absolute difference, 2.6 percent; 95 percent confidence interval, - 4.6 to 9.8). Graft patency in a randomized subgroup of patients was 93 percent after on-pump surgery and 91 percent after off-pump surgery (absolute difference, 2.0 percent; 95 percent confidence interval, - 6.5 to 10.4). On-pump surgery was associated with $1,839 in additional direct costs per patient ($14,908 vs. $13,069--a difference of 14.1 percent) and an increase in quality-adjusted years of life of 0.83 as compared with 0.82 (difference, 0.01 year; 95 percent confidence interval, - 0.03 to 0.04). Off-pump surgery was more cost effective than on-pump surgery in 95 percent of bootstrap estimates. CONCLUSIONS: In low-risk patients, there was no difference in cardiac outcome at one year between those who underwent on-pump bypass surgery and those who underwent off-pump surgery. Off-pump surgery was more cost effective.

Cardiopulmonary Bypass↗

PubMed2005

Incorporating gene-specific variation when inferring and evaluating optimal evolutionary tree topologies from multilocus sequence data.

Because of the increase of genomic data, multiple genes are often available for the inference of phylogenetic relationships. The simple approach for combining multiple genes from the same taxon is to concatenate the sequences and then ignore the fact that different positions in the concatenated sequence came from different genes. Here, we discuss two criteria for inferring the optimal tree topology from data sets with multiple genes. These criteria are designed for multigene data sets where gene-specific evolutionary features are too important to ignore. One criterion is conventional and is obtained by taking the sum of log-likelihoods over all genes. The other criterion is obtained by dividing the log-likelihood for a gene by its sequence length and then taking the arithmetic mean over genes of these ratios. A similar strategy could be adopted with parsimony scores. The optimal tree is then declared to be the one for which the sum or the arithmetic mean is maximized. These criteria are justified within a two-stage hierarchical framework. The first level of the hierarchy represents gene-specific evolutionary features, and the second represents site-specific features for given genes. For testing significance of the optimal topology, we suggest a two-stage bootstrap procedure that involves resampling genes and then resampling alignment columns within resampled genes. An advantage of this procedure over concatenation is that it can effectively account for gene-specific evolutionary features. We discuss the applicability of the two-stage bootstrap idea to the Kishino-Hasegawa test and the Shimodaira-Hasegawa test.

Biological Evolution↗

PubMed2005

Placing confidence limits on the molecular age of the human-chimpanzee divergence.

Molecular clocks have been used to date the divergence of humans and chimpanzees for nearly four decades. Nonetheless, this date and its confidence interval remain to be firmly established. In an effort to generate a genomic view of the human-chimpanzee divergence, we have analyzed 167 nuclear protein-coding genes and built a reliable confidence interval around the calculated time by applying a multifactor bootstrap-resampling approach. Bayesian and maximum likelihood analyses of neutral DNA substitutions show that the human-chimpanzee divergence is close to 20% of the ape-Old World monkey (OWM) divergence. Therefore, the generally accepted range of 23.8-35 millions of years ago for the ape-OWM divergence yields a range of 4.98-7.02 millions of years ago for human-chimpanzee divergence. Thus, the older time estimates for the human-chimpanzee divergence, from molecular and paleontological studies, are unlikely to be correct. For a given the ape-OWM divergence time, the 95% confidence interval of the human-chimpanzee divergence ranges from -12% to 19% of the estimated time. Computer simulations suggest that the 95% confidence intervals obtained by using a multifactor bootstrap-resampling approach contain the true value with >95% probability, whether deviations from the molecular clock are random or correlated among lineages. Analyses revealed that the use of amino acid sequence differences is not optimal for dating human-chimpanzee divergence and that the inclusion of additional genes is unlikely to narrow the confidence interval significantly. We conclude that tests of hypotheses about the timing of human-chimpanzee divergence demand more precise fossil-based calibrations.

Animals↗

PubMed2006

A likelihood approach to analysis of network data.

Biological, sociological, and technological network data are often analyzed by using simple summary statistics, such as the observed degree distribution, and nonparametric bootstrap procedures to provide an adequate null distribution for testing hypotheses about the network. In this article we present a full-likelihood approach that allows us to estimate parameters for general models of network growth that can be expressed in terms of recursion relations. To handle larger networks we have developed an importance sampling scheme that allows us to approximate the likelihood and draw inference about the network and how it has been generated, estimate the parameters in the model, and perform parametric bootstrap analysis of network data. We illustrate the power of this approach by estimating growth parameters for the Caenorhabditis elegans protein interaction network.

Animals↗

PubMed2000

Compact stellarators with modular coils.

Compact stellarator designs with modular coils and only two or three field periods are now available; these designs have both good stability and quasiaxial symmetry providing adequate transport for a magnetic fusion reactor. If the bootstrap current assumes theoretically predicted values a three field period configuration is optimal, but if that net current turns out to be lower, a device with two periods and just 12 modular coils might be better. There are also attractive designs with quasihelical symmetry and four or five periods whose properties depend less on the bootstrap current. Good performance requires that there be a satisfactory magnetic well in the vacuum field, which is a property lacking in a stellarator-tokamak hybrid that has been proposed for a proof of principle experiment. In this paper, we present an analysis of stability for these configurations that is based on a mountain pass theorem asserting that, if two solutions of the problem of magnetohydrodynamic equilibrium can be found, then there has to be an unstable solution. We compare results of our theory of equilibrium, stability, and transport with recently announced measurements from the large LHD experiment in Japan.

Journal Article↗

PubMed2004

Early evolution within kinetoplastids (euglenozoa), and the late emergence of trypanosomatids.

Many important relationships amongst kinetoplastids, including the position of trypanosomatids, remain uncertain, with limited taxon sampling of markers other than small subunit ribosomal RNA (SSUrRNA). We report gene sequences for cytosolic heat shock proteins 90 and/or 70 (HSP90, HSP70) from the potentially early-diverging kinetoplastids Ichthyobodo necator and Rhynchobodo sp., and from bodonid clades '2' (Parabodonidae) and '3' (Eubodonidae). Some of the new cytosolic HSP70 sequences represent a distinct paralog family (HSP70-B), which is related to yet another paralog known from trypanosomatids (HSP70-C). The (HSP70-B, HSP70-C) clade seemingly diverged before the separation between kinetoplastids and diplonemids. Protein phylogenies support the basal placement of Ichthyobodo within kinetoplastids. Unexpectedly, Rhynchobodo usually forms the next most basal group, separated from the clade '1' bodonids with which it has been allied. Bootstrap support is often weak, but the possibility that Rhynchobodo represents a separate early-diverging lineage within core kinetoplastids deserves further testing. Trypanosomatids always fall remote from the root of kinetoplastids, forming a specific relationship with bodonid clades 2 (and 3), generally with strong bootstrap support. These protein trees with improved taxon sampling provide the best evidence to date for a 'late' emergence of trypanosomatids, contradicting recent SSUrRNA-based proposals for a relatively early divergence of this group.

Amino Acid Sequence↗

PubMed2002

Random amplified polymorphic DNA markers for discriminating Cochliomyia hominivorax from C. macellaria (Diptera: Calliphoridae).

The screwworm, Cochliomyia hominivorax (Coquerel), is one of the most important pests of livestock in the Western Hemisphere. During early immature stages it is morphologically very similar (first instars are virtually indistinguishable) to the secondary screwworm, C. macellaria (Fabricius). Here, the utility of the random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) was explored as a technique for developing molecular genetic markers for these two species. Of the 120 arbitrary primers screened, 21 primers produced markers that were further investigated. Seven of the 21 primers produced clear and reproducible markers that were tested with DNA of five individuals from four populations of each species; five of these primers showed 12 RAPD markers that differentiated the species in all populations. Analyses of data from these seven primers also suggested that intraspecific polymorphisms exist that could be useful in distinguishing populations of screwworms. Some population genetic tools, such as genetic distance, cluster analysis and bootstrapping, were used to statistically explore these polymorphisms. The resulting statistics showed 100% support for the ability of RAPD-PCR to discriminate between the two species. Bootstrapping with data from one of the genetic distance calculations produced a tree with all individual screwworms in the correct populations, indicating that RAPD-PCR has promise for displaying intraspecific genetic variation that could be used in establishing the general geographic origin of screwworm samples.

Animals↗

PubMed2005

Reliable exposure assessment strategies for physical ergonomics stressors in construction and other non-routinized work.

The objective of this research was to provide guidelines for the reliable assessment of ergonomics exposures in non-routinized work. Using a discrete-interval observational sampling approach, two or three observers collected a total of 5852 observations on tasks performed by three construction trades (iron workers, carpenters and labourers) for periods of several weeks. For each observation, nine exposure variables associated with awkward body postures, tool use and load handling were recorded. The frequency of exposure to each variable was calculated for each worker during each of the tasks on each of the days. ANOVA was used to assess the importance of task in explaining between-worker and within-worker variability in exposures across days. A statistical re-sampling method (bootstrap) was used to evaluate the reliability of exposure estimates for groups of workers performing the same task for different sampling periods. Most exposures were found to vary significantly across construction tasks within trade, and between-worker exposure variability was generally smaller than within-worker exposure variability within task. Bootstrapping showed that the reliability of the group estimates exposure for the most variable exposures within task tended to improve as the assessment periods approached 5-6 d, with marginal improvements for longer assessment periods. Reliable group estimates of exposure for the least variable exposures within task were obtained with 1 or 2 d of observation. The results of this study demonstrate that an initial estimate of the important environmental or task sources of exposure variability can be used to develop an efficient sampling strategy that provides reliable estimates of ergonomics exposures during non-routinized work.

Adult↗

PubMed2001

Stability of psychometric questionnaires.

In 1999, Wilson and Batterham proposed a new approach to assessing the test-retest stability of psychometric questionnaires. They recommended assessing the proportion of agreement - that is, the proportion of participants that record the same response to an item - using a test-retest design. They went on to use a bootstrapping technique to estimate the uncertainty of the proportion of agreement. The aims of this short communication are (1) to demonstrate that the sampling distribution of the proportion of agreement is well known (the binomial distribution), making the technique of 'bootstrapping' redundant, and (2) to suggest a much simpler, more sensitive method of assessing the stability of a psychometric questionnaire, based on the test-retest differences (within-individuals) for each item. Adopting methods similar to Wilson and Batterham, 97 sport students completed the Social Physique Anxiety Scale on two occasions. Test-retest differences were calculated for each item. Our results show that the proportion of agreement ignores the nature of disagreement. Items 4 and 11 showed similar agreement (44.3% and 43.3% respectively), but 89 of the participants (91.8%) differed by just +/-1 point when responding to item 4, indicating a relatively stable item. In contrast, only 78 of the participants (80.4%) recorded a difference within +/- 1 point when responding to item 11, suggesting quite contrasting stability for the two items. We recommend that, when assessing the stability of self-report questionnaires using a 5-point scale, most participants (90%) should record test-retest differences within a reference value of +/- 1.

Adult↗

PubMedDate not supplied

Fast mapping of verbs by children with specific language impairment.

Two studies examined preschoolers' ability to assign verb interpretations to nonsense words encountered in conjunction with novel actions. Experiment 1 examined the ability of children with specific language impairment (SLI) and younger, normally developing peers to glean a very interpretation when the name of the figure performing the novel action was already known. The two groups of children performed in a similar, accurate fashion. Experiment 2 required preschoolers to rely exclusively on morphosyntactic information to determine whether the novel word represented an object or action. When provided with redundant morphosyntactic cues, children with SLI and language- and age-matched peers succeeded in identifying the novel words that referred to objects but not those that referred to actions. Only the age-matched normal peers were above chance levels when a noun interpretation depended on a single grammatical morpheme (e.g., 'We want the koob' versus 'We want to koob'). The findings suggest that preschoolers, whether or not they have language impairment, have difficulty using morphosyntactic information to bootstrap verbs. Furthermore, redundant but not single morphosyntactic cues facilitate the bootstrapping of nouns.

Child↗

PubMed2026

Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.

BACKGROUND: COVID-19 has been closely associated with coagulation abnormalities. However, existing biomarkers, including D-dimer and fibrin degradation products (FDP), exhibit limited accuracy in stratifying disease severity and predicting long-term clinical outcomes. OBJECTIVES: This study aimed to use proteomic analysis to identify plasma biomarkers associated with COVID-19 severity and prognosis, and validate their predictive utility for mortality and thromboembolic complications. METHODS: Plasma proteomic profiles were analyzed across three COVID-19 severity classes. Differential expression analysis and functional analysis were performed. Clustering analysis was used to identify proteins correlated with disease severity. Candidate biomarkers were validated in an independent cohort. Predictive performance of the biomarkers for mortality, sepsis and venous thromboembolism was evaluated using bootstrap-corrected ROC analyses and multivariable regression analyses. RESULTS: Proteomic analysis revealed progressive involvement of the coagulation and complement pathway with increasing disease severity. SERPINA1 and CD59 were identified as candidate biomarkers and exhibited significantly higher plasma levels in severe cases. Bootstrap-corrected ROC analyses demonstrated strong predictive performance: SERPINA1 achieved AUCs of 0.775 and 0.924 for 30-day and 12-month mortality, and CD59 achieved AUCs of 0.720 for sepsis; the combined model further improved prediction of 12-month mortality (AUC 0.946) and sepsis (AUC 0.904), outperforming D-dimer and FDP. Multivariable regression confirmed their independent prognostic value. CONCLUSION: This exploratory study identifies SERPINA1 and CD59 as candidate prognostic biomarkers in COVID-19, highlighting the role of coagulation and complement-related pathways in disease severity and warranting further prospective validation.

Humans↗

PubMed2004

Development of probabilistic emission inventories of air toxics for Jacksonville, Florida, USA.

Probabilistic emission inventories were developed for 1,3-butadiene, mercury (Hg), arsenic (As), benzene, formaldehyde, and lead for Jacksonville, FL. To quantify inter-unit variability in empirical emission factor data, the Maximum Likelihood Estimation (MLE) method or the Method of Matching Moments was used to fit parametric distributions. For data sets that contain nondetected measurements, a method based upon MLE was used for parameter estimation. To quantify the uncertainty in urban air toxic emission factors, parametric bootstrap simulation and empirical bootstrap simulation were applied to uncensored and censored data, respectively. The probabilistic emission inventories were developed based on the product of the uncertainties in the emission factors and in the activity factors. The uncertainties in the urban air toxics emission inventories range from as small as -25 to +30% for Hg to as large as -83 to +243% for As. The key sources of uncertainty in the emission inventory for each toxic are identified based upon sensitivity analysis. Typically, uncertainty in the inventory of a given pollutant can be attributed primarily to a small number of source categories. Priorities for improving the inventories and for refining the probabilistic analysis are discussed.

Air Pollutants↗

PubMed2006

Estimating the frequency distributions of particulate matter and their metal elements in a temple.

Air quality inside Asian temples is typically poor because of the burning of incense. This study measured and analyzed concentrations of fine (PM2.5) and coarse (PM2.5-10) particulate matter and their metal elements inside a temple in central Taiwan. Experimental results showed that the concentrations of metals Cd, Ni, Pb, and Cr inside the temple were higher than those at rural, suburban, urban, and industrial areas in other studies. Three theoretical parent distributions (lognormal, Weibull, and gamma) were used to fit the measured data. The lognormal distribution was the most appropriate distribution for representing frequency distributions of PM10, PM2.5, and their metal elements. Furthermore, the central limit theorem, H-statistic-based scheme, and parametric and nonparametric bootstrap methods were used to estimate confidence intervals for mean pollutant concentrations. The estimated upper confidence limits (UCLs) of means between different methods were very consistent, because the sample coefficient of variation (CV) was < 1. When the sample CV was > 1, the UCL based on H-statistical method tended to overestimate the UCLs when compared with other methods. Confidence intervals for pollutant concentrations at different percentiles were evaluated using parametric and nonparametric bootstrap methods. The probabilities of pollutants exceeding a critical concentration were also calculated.

Air Pollutants↗

PubMed1997

Multiple-time-point dissolution specifications for a sampling acceptance plan.

In dissolution testing, multiple dissolution measurements at specific time points are used to obtain the dissolution characteristics for most extended-release and some immediate-release drug products. This paper presents a general procedure for defining specifications by a multivariate confidence region or by simultaneous confidence limits on the dissolution values of individual time points. The confidence regions and simultaneous confidence limits were estimated using two approaches: the first approach assumed a multivariate normal distribution on the multiple dissolution values and the second approach used the bootstrap resampling method. The multivariate confidence region was constructed using the Hotelling's T2 statistic (equivalently, Mahalanobis distance D2), and the simultaneous confidence limits were based on the Mahalanobis statistic as well as on the Bonterroni adjustment. The Mahalanobis simultaneous confidence limits specification criteria have the overall false out-of-specification rate too low in both parametric and bootstrap approaches.

Chemistry, Pharmaceutical↗