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PubMed2004

Statistical evaluation of learning curve effects in surgical trials.

Randomized controlled trials (RCTs) in surgery have been impeded by concerns that improvements in the technical performance of a new technique over time (a "learning curve") may distort comparisons. The statistical assessment of learning curves in trials has received little attention. In this paper, we discuss what a learning curve effect is, the factors which effect it, how to display it, and how to incorporate the learning effect into the trial analysis. Bayesian hierarchical models are proposed to adjust the trial results for the existence of a learning curve effect. The implications for trial evaluation and data collection are considered.

Bayes Theorem↗

PubMed2006

Randomized controlled trial of single-operator vs. two-operator ultrasound guidance for internal jugular central venous cannulation.

OBJECTIVES: Use of ultrasound guidance for central line placement generally requires two operators: one to hold the transducer and the other to guide the needle. The authors propose a single-operator technique and compare it with the two-operator technique for placement of internal jugular central lines. METHODS: This was a randomized clinical trial conducted from June to September 2004 in a U.S. urban teaching hospital. Enrollment packets were randomized to dynamic single operator (D1) and dynamic two operator (D2). The procedure was performed under ultrasound visualization in the transverse plane. The primary outcome measure was cannulation success. A complete Bayesian analysis using noninformative priors to estimate the probability of similarity of outcomes for D1 and D2 was performed. All variables are reported with 95% confidence intervals (CIs) where appropriate. RESULTS: Forty-four patients were enrolled from the emergency department and intensive care unit. Twenty-three patients were randomized to D1, and 21 to D2. Cannulation success was 96% (95% CI = 85% to 100%) for D1 and 95% (95% CI = 83% to 100%) for D2. There was a 90% probability that the success rates of these two groups differed by less than 10% of each other. CONCLUSIONS: This one-person technique appears to be equivalent to the standard two-person technique for successful ultrasound-guided internal jugular central venous catheterization with respect to overall success.

Catheterization, Central Venous↗

PubMed2003

A Bayesian argument against rigid cut-offs in electrodiagnosis of median neuropathy at the wrist.

BACKGROUND: Nerve conduction (NC) tests, using rigid cut-offs separating normal from abnormal test values, are commonly used to confirm median neuropathy at the wrist (MNW). The authors studied patients with clinically defined mild MNW and a normal median distal motor latency to determine 1) how much sensory or mixed NC test results increase (or decrease) the probability of MNW and 2) the NC test values required to confirm (or exclude) MNW for the range of pretest probabilities of MNW. METHODS: Palmar, digit 4 (D4), and digit 2 (D2) median NC tests were reviewed in 125 hands with mild carpal tunnel syndrome (CTS) and 100 control hands with musculoskeletal pain. Receiver operating characteristic curves and interval likelihood ratios were plotted for the three tests. Using Bayes theorem, post-test probability of MNW was then determined for the range of pretest probabilities and NC test values. RESULTS: Receiver operating characteristic curves showed that for a set specificity of 97%, palmar and D4 studies had higher electrodiagnostic utility than D2 studies with cut-off test values (sensitivities of 0.3 msec, 64.0%; 0.4 msec, 71.2%; and 50 m/sec, 44.8%). However, Bayesian analysis showed that to confirm MNW more conservative cut-off values (palmar 0.5 msec, D4 0.7 msec, D2 44 m/sec) were required for pretest probabilities or=75%. Conversely, normal test values could exclude MNW only for pretest probabilities <25%. CONCLUSIONS: For a given NC test value, post-test probability of MNW can be determined from the estimated pretest probability (derived from clinical data), interval likelihood ratios, and Bayes theorem. Use of rigid cut-off values to confirm MNW is problematic, because more conservative cut-offs are required for low pretest probability. Conversely, NC tests with sensitivity <95% cannot exclude MNW when pretest probability is high.

Adolescent↗

PubMed1998

Predictive performance of a vancomycin-aminoglycoside population model.

OBJECTIVE: To evaluate the Wragge-Cooper method of predicting vancomycin serum concentrations utilizing knowledge of aminoglycoside pharmacokinetic parameters in general medicine and intensive care unit populations, and to develop a revised model if necessary. DESIGN: This study consists of two phases evaluating 50 adults receiving concurrent vancomycin and aminoglycoside therapy. Patients were identified by a retrospective review of medical records. Bayesian analysis of measured serum aminoglycoside and vancomycin concentrations was performed to determine the individualized pharmacokinetic parameters. Phase I of the study tested the predictive performance of a published model incorporating aminoglycoside elimination (Wragge-Cooper) in 25 patients (group 1), and a revised model was developed. Phase II determined the predictive performance of the revised model (revised) and its performance relative to the Wragge-Cooper model and a traditional model incorporating estimated creatinine clearance (traditional) in an additional 25 patients (group 2). SETTING: Two tertiary care university teaching hospitals. MAIN OUTCOME MEASURES: The predictive performance of the models was determined by comparing predicted with measured vancomycin serum concentrations. Bias and precision were evaluated by calculating the mean prediction error (ME) and mean absolute error (MAE), respectively. Linear regression was performed to determine relationships between parameters. RESULTS: The Wragge-Cooper model consistently underpredicts vancomycin serum concentrations in general medicine and intensive care unit populations (ME = -5.18, MAE = 6.63). Relative predictive performance analysis indicates no significant difference in bias or precision between the traditional and Wragge-Cooper models (delta ME 1.17, delta MAE -0.80). Regression analysis of individualized aminoglycoside and vancomycin elimination derived from patients in group 1 reveals the following relationship: vancomycin k10 (1/h) = 0.081 + 1.037ke,amg, r = 0.73. The revised model is significantly less biased and more precise compared with the traditional model (delta ME -4.48; delta MAE 1.22), and is significantly less biased (delta ME 4.29) but no more precise than the Wragge-Cooper model (delta MAE -0.58), using patients from group 2. CONCLUSIONS: The revised model is an accurate method of predicting vancomycin serum concentrations in both general medicine and intensive care unit populations. Use of this model enables individualization of vancomycin dosage in patients receiving concurrent aminoglycoside therapy and minimizes vancomycin serum concentration monitoring.

Adult↗

PubMedDate not supplied

A brief primer on automated signal detection.

BACKGROUND: Statistical techniques have traditionally been underused in spontaneous reporting systems used for postmarketing surveillance of adverse drug events. Regulatory agencies, pharmaceutical companies, and drug monitoring centers have recently devoted considerable efforts to develop and implement computer-assisted automated signal detection methodologies that employ statistical theory to enhance screening efforts of expert clinical reviewers. OBJECTIVE: To provide a concise state-of-the-art review of the most commonly used automated signal detection procedures, including the underlying statistical concepts, performance characteristics, and outstanding limitations, and issues to be resolved. DATA SOURCES: Primary articles were identified by MEDLINE search (1965-December 2002) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: Commonly used methods of automated signal detection are self-contained and involve screening large databases of spontaneous adverse event reports in search of interestingly large disproportionalities or dependencies between significant variables, usually single drug-event pairs, based on an underlying model of statistical independence. The models vary according to the underlying model of statistical independence and whether additional mathematical modeling using Bayesian analysis is applied to the crude measures of disproportionality. There are many potential advantages and disadvantages of these methods, as well as significant unresolved issues related to the application of these techniques, including lack of comprehensive head-to-head comparisons in a single large transnational database, lack of prospective evaluations, and the lack of gold standard of signal detection. CONCLUSIONS: Current methods of automated signal detection are nonclinical and only highlight deviations from independence without explaining whether these deviations are due to a causal linkage or numerous potential confounders. They therefore cannot replace expert clinical reviewers, but can help them to focus attention when confronted with the difficult task of screening huge numbers of drug-event combinations for potential signals. Important questions remain to be answered about the performance characteristics of these methods. Pharmacovigilance professionals should take the time to learn the underlying mathematical concepts in order to critically evaluate accumulating experience pertaining to the relative performance characteristics of these methods that are incompletely defined.

Automation↗

PubMed1997

Utility of lactate dehydrogenase vs radiographic severity in the differential diagnosis of Pneumocystis carinii pneumonia.

STUDY OBJECTIVES: In patients with HIV infection, serum lactate dehydrogenase (LDH) level is commonly stated to be more elevated in Pneumocystis carinii pneumonia (PCP) than in non-PCP. We hypothesized that LDH level reflects radiographic extent and severity of pneumonia rather than P carinii infection specifically and therefore is not useful in the differential diagnosis of lung infections in AIDS. DESIGN: We compared radiographic features and LDH values in 93 sequential patients with HIV infection and a new hospital admission for pneumonia (53 PCP and 40 non-PCP) after excluding all patients with other potential causes for elevated LDH levels. The chest radiograph was graded using a quantitative scale (0 to 24) to assess radiographic extent and severity of pneumonia by two independent observers in blinded fashion. The relationship between radiographic score and hospital admission LDH level was analyzed by linear regression and Bayesian analysis was applied to different LDH ranges to calculate the clinical value of LDH measurements. SETTING: Tertiary care teaching hospital and regional AIDS referral center. RESULTS: Mean LDH level was higher in the PCP group (1.217 +/- 88 U/L compared with 776 +/- 55 U/L; p < 0.001), as was mean radiographic score (12.4 +/- 0.6 for PCP compared with 6.3 +/- 0.5 for non-PCP; p < 0.001). For the whole sample of 93, LDH level was significantly related to chest radiographic score (r = 0.43, p < 0.0001). Significant overlap occurred between the two groups at all levels of LDH such that no cutoff level could be established that impacted significantly on posttest probability of PCP, whereas a radiographic score of > 12 yielded a 96% posttest probability of PCP. CONCLUSIONS: Serum LDH level reflects the degree of radiographic abnormality and is elevated in both PCP and non-PCP pneumonia to an extent that limits its utility in differentiating the two processes in hospitalized patients. The extent of radiographic involvement more clearly distinguishes the two conditions.

AIDS-Related Opportunistic Infections↗

PubMed2006

Association mapping of complex trait loci with context-dependent effects and unknown context variable.

A novel method for Bayesian analysis of genetic heterogeneity and multilocus association in random population samples is presented. The method is valid for quantitative and binary traits as well as for multiallelic markers. In the method, individuals are stochastically assigned into two etiological groups that can have both their own, and possibly different, subsets of trait-associated (disease-predisposing) loci or alleles. The method is favorable especially in situations when etiological models are stratified by the factors that are unknown or went unmeasured, that is, if genetic heterogeneity is due to, for example, unknown genes x environment or genes x gene interactions. Additionally, a heterogeneity structure for the phenotype does not need to follow the structure of the general population; it can have a distinct selection history. The performance of the method is illustrated with simulated example of genes x environment interaction (quantitative trait with loosely linked markers) and compared to the results of single-group analysis in the presence of missing data. Additionally, example analyses with previously analyzed cystic fibrosis and type 2 diabetes data sets (binary traits with closely linked markers) are presented. The implementation (written in WinBUGS) is freely available for research purposes from http://www.rni.helsinki.fi/ approximately mjs/.

Alleles↗

PubMed2005

Angiosperm divergence times: the effect of genes, codon positions, and time constraints.

An understanding of the evolution of modern terrestrial ecosystems requires an understanding of the dynamics associated with angiosperm evolution, including the timing of their origin and diversification into their extraordinary present-day diversity. Molecular estimates of angiosperm age have varied widely, and many substantially predate the Early Cretaceous fossil appearance of the group. In this study, the effect of different genes, codon positions, and chronological constraints on node ages are examined on divergence time estimates across seed plants, with a special focus on angiosperms. Penalized likelihood was used to estimate divergence times on a phylogenetic hypothesis for seed plants derived from Bayesian analysis, with branch lengths estimated with maximum likelihood. The plastid genes atpB, psaA, psbB, and rbcL were used individually and in combination, using first and second, third, and the three codon positions, including and excluding age constraints on 20 nodes derived from a critical examination of the land-plant fossil record. The optimal level of rate smoothing according to each unconstrained and constrained dataset was obtained with penalized likelihood. Tests for a molecular clock revealed significantly unclocklike rates in all datasets. Addition of fossil constraints resulted in even greater departures from constancy. Consistently with significant deviations from a clock, estimated optimal smoothing values were low, but a strict correlation between rate heterogeneity and optimal smoothing value was not found. Age estimates for nodes across the phylogeny varied, sometimes substantially, with gene and codon position. Nevertheless, estimates based on the four concatenated genes are very similar to the mean of the four individual gene estimates. For any given node, unconstrained age estimates are more variable than constrained estimates and are frequently younger than well-substantiated fossil members of the clade. Constrained estimates of ages of clades are older than unconstrained estimates and oldest fossil representatives, sometimes substantially so. Angiosperm age estimates decreased as rate smoothing increased. Whereas the range of unconstrained angiosperm age estimates spans the fossil age of the clade, the range of constrained estimates is narrower (and older) than the earliest angiosperm fossils. Results unambiguously indicate the relevance of constraints in reducing the variability of ages derived from different partitions of the data and diminishing the effect of the smoothing parameter. Constrained optimizations of divergence times and substitution rates across the phylogeny suggest appreciably different evolutionary dynamics for angiosperms and for gymnosperms. Whereas the gymnosperm crown group originated shortly after the origin of seed plants, a long time elapsed before the origin of crown group angiosperms. Although absolute age estimates of angiosperms and angiosperm clades are older than their earliest fossils, the estimated pace of phylogenetic diversification largely agrees with the rapid appearance of angiosperm lineages in stratigraphic sequences.

Base Sequence↗

PubMed2006

Genetic characterization of St. Louis encephalitis virus isolated from human in São Paulo, Brazil.

The molecular characterization of SPH253157, a new strain of St. Louis encephalitis virus (SLEV), isolated in 2004 from the first case of human infection recognized in the state of São Paulo, Brazil, is reported. The patient, presenting a febrile illness without neurological involvement, was hospitalized as a probable case of dengue fever. Genomic RNA was isolated from the supernatant of C6/36 cells infected with acute phase-serum specimen of the patient and the envelope gene was amplified by reverse-transcription-polymerase chain reaction. The complete nucleotide sequence of the envelope gene of this isolate was directly sequenced from the amplified products and compared with other Brazilian and American SLEV strains. Phylogenetic analyses were carried out under maximum likelihood criterion with outgroups both included and excluded. Outgroups comprised four flavivirus of the Japanese encephalitis group. Phylogeny also included Bayesian analysis. The results indicated that the new SLEV isolate belongs to lineage III, being closely related to an Argentinean strain recovered from Culex sp. in 1979. It is concluded that there are at least 3 lineages of SLEV in Brazil.

Brazil↗

PubMed2004

Using Biowin, Bayes, and batteries to predict ready biodegradability.

Whether or not a given chemical substance is readily biodegradable is an important piece of information in risk screening for both new and existing chemicals. Despite the relatively low cost of Organization for Economic Cooperation and Development tests, data are often unavailable and biodegradability must be estimated. In this paper, we focus on the predictive value of selected Biowin models and model batteries using Bayesian analysis. Posterior probabilities, calculated based on performance with the model training sets using Bayes' theorem, were closely matched by actual performance with an expanded set of 374 premanufacture notice (PMN) substances. Further analysis suggested that a simple battery consisting of Biowin3 (survey ultimate biodegradation model) and Biowin5 (Ministry of International Trade and Industry [MITI] linear model) would have enhanced predictive power in comparison to individual models. Application of the battery to PMN substances showed that performance matched expectation. This approach significantly reduced both false positives for ready biodegradability and the overall misclassification rate. Similar results were obtained for a set of 63 pharmaceuticals using a battery consisting of Biowin3 and Biowin6 (MITI nonlinear model). Biodegradation data for PMNs tested in multiple ready tests or both inherent and ready biodegradation tests yielded additional insights that may be useful in risk screening.

Bayes Theorem↗

PubMed2004

A bayesian approach to parameter estimation for a crayfish (Procambarus spp.) bioaccumulation model.

Bioaccumulation models are used to describe chemical uptake and clearances by organisms. Averaged input parameter values are traditionally used and yield point estimates of model outputs. Hence, the uncertainty and variability of model predictions are ignored. Probabilistic modeling approaches, such as Monte Carlo simulation and the Bayesian method, have been recommended by the U.S. Environmental Protection Agency to provide a quantitative description of the degree of uncertainty and/or variability in risk estimates in ecological hazards and human health effects. In this study, a Bayesian analysis was conducted to account for the combined uncertainty and variability of model parameters in a crayfish bioaccumulation model. After a 5-d exposure in the LaBranche Wetlands (LA, USA), crayfish were analyzed for polycyclic aromatic hydrocarbon concentrations and lipid fractions. The posterior distribution of model parameters were derived from the joint posterior parameter distributions using a Markov chain Monte Carlo approach and the experimental data. The results were then used to predict the distribution of chrysene concentration versus time in the crayfish to compare the predicted ranges at the different study sites.

Animals↗

PubMed2005

Genetic parameters of fertility in two lines of rabbits with different reproductive potential.

A Bayesian analysis with a threshold model was performed for fertility defined as a binary trait (1 = successful mating, 0 = unsuccessful mating) in two populations of rabbits of different reproductive potential and different genetic origin: Line P selected for litter size and Line C selected for growth rate. There were 20,793 records of natural mating (86.2% successful) in Line C between 1983 and 2003, and 17,548 records (80.5% successful) in Line P, between 1992 and 2003. Data related to 5,388 and 3,848 females and 1,021 and 685 males in Lines C and P, respectively. The pedigree included 6,409 and 4,533 individuals in Lines C and P, respectively. The binary response was modeled under a probit approach. The model for the latent variable included male and female additive genetic effects, male and female permanent environmental effects, and the year-season and physiological status of the female (nulliparous, multiparous lactating, or multiparous nonlactating) as systematic effects. Means (standard deviation in parentheses) of the estimated marginal posterior distribution (EMPD) of male heritability were 0.013 (0.006) and 0.010 (0.008) in Lines C and P, respectively, and those of EMPD of female heritability were 0.056 (0.013) and 0.062 (0.018) in Lines C and P, respectively. Means of the EMPD of the proportion of the phenotypic variance due to environmental male and female effects were, respectively, 0.031 (0.007) and 0.128 (0.018) in Line C and 0.053 (0.010) and 0.231 (0.024) in Line P. Means (standard deviations in parentheses) of the EMPD of genetic correlation between male and female fertility were 0.733 (0.197) in Line C and 0.434 (0.381) in Line P. The posterior distribution of genetic correlations presents a huge dispersion, and the estimates should be taken with caution because of the almost negligible estimate of the male genetic component. Results indicate that little genetic variation exists for female fertility, and practically none for male fertility. It would, therefore, be possible to improve reproductive performance by including female fertility in a breeding program, but response to selection would be very small.

Animals↗

PubMed2006

The effect of ignoring individual heterogeneity in Weibull log-normal sire frailty models.

The objective of this study was, by means of simulation, to quantify the effect of ignoring individual heterogeneity in Weibull sire frailty models on parameter estimates and to address the consequences for genetic inferences. Three simulation studies were evaluated, which included 3 levels of individual heterogeneity combined with 4 levels of censoring (0, 25, 50, or 75%). Data were simulated according to balanced half-sib designs using Weibull log-normal animal frailty models with a normally distributed residual effect on the log-frailty scale. The 12 data sets were analyzed with 2 models: the sire model, equivalent to the animal model used to generate the data (complete sire model), and a corresponding model in which individual heterogeneity in log-frailty was neglected (incomplete sire model). Parameter estimates were obtained from a Bayesian analysis using Gibbs sampling, and also from the software Survival Kit for the incomplete sire model. For the incomplete sire model, the Monte Carlo and Survival Kit parameter estimates were similar. This study established that when unobserved individual heterogeneity was ignored, the parameter estimates that included sire effects were biased toward zero by an amount that depended in magnitude on the level of censoring and the size of the ignored individual heterogeneity. Despite the biased parameter estimates, the ranking of sires, measured by the rank correlations between true and estimated sire effects, was unaffected. In comparison, parameter estimates obtained using complete sire models were consistent with the true values used to simulate the data. Thus, in this study, several issues of concern were demonstrated for the incomplete sire model.

Animals↗

PubMed2026

The Evolutionary Significance of Leaf Nodulation: Evidence from Ardisia and Its Relatives (Primulaceae: Myrsinoideae).

Interactions between plants and microorganisms have long been a central topic in biological research. Bacterial symbiosis on leaf surfaces represents a distinctive and mutually beneficial system within the phyllosphere microbiome. Leaf nodules are the visible manifestation of the symbiosis and confer ecological advantages to host plants by enhancing host resistance against pathogens and herbivores. It has been hypothesized that these advantages promote higher diversification rates in host lineages, but this remains uncertain. Ardisia subg. Crispardisia and its close relatives (Amblyanthopsis and Amblyanthus) within Primulaceae are typical plant groups with leaf nodule symbiosis, making them an ideal system for testing this hypothesis. In this study, we conducted extensive sampling of "Ardisioids" (Ardisia and its allies) and reconstructed their phylogenetic relationships and evolutionary history using plastid genomes and nuclear datasets (i.e., nuclear ribosomal DNA (nrDNA) and genome-wide single nucleotide polymorphisms (SNPs)). We clarified the phylogenetic positions of several "Ardisioids" genera (e.g., Sadiria, Tapeinosperma, Amblyanthus, and Amblyanthopsis) and multiple subgenera within Ardisia. We further detected a rapid radiation during the middle Miocene in Ardisia and its allies. Notably, we found that the leaf-nodulated clade appears to have originated during this period, approximately 11-8 Ma. BAMM (Bayesian Analysis of Macroevolutionary Mixtures) analyses revealed elevated diversification rates in leaf-nodulated lineages, while HiSSE (Hidden State Speciation and Extinction) analyses indicated that leaf nodule symbiosis might have increased speciation rates without significantly affecting extinction rates. These results provide strong evidence that leaf nodule symbiosis, together with other abiotic and biotic factors, represents a key evolutionary innovation that has promoted diversification in Ardisia and its close relatives.

diversification rate↗

PubMedDate not supplied

Molecular phylogeny of parmotremoid lichens (Ascomycota, Parmeliaceae).

Parmotrema is one of the larger genera segregated from Parmelia s. lat. Additional genera recently have been segregated from this large genus based mainly on morphological and chemical features. We have employed molecular data from three genes to continue a revision of the generic concept within the parmelioid lichens. A Bayesian analysis of nuclear ITS, LSU rDNA and mitochondrial SSU rDNA sequences was performed. The genera Canomaculina, Concamerella, Parmelaria and Rimelia appear nested within Parmotrema. Alternative hypotheses to maintain the independence of Canomaculina, Concamerella and Rimelia are shown to be highly unlikely and are rejected. As a consequence these three genera are reduced to synonymy with Parmotrema. An alternative topology segregating Parmelaria from Parmotrema s. lat. cannot be rejected with the dataset at hand. However we have established that this genus is closely related to Parmotrema rather than to cetrarioid species as was considered previously. The revised genus Parmotrema includes species that have an upper cortex consisting of a palisade plectenchyma or rarely paraplectenchyma with vaults, have a pored or fenestrated epicortex, lack pseudocyphellae, have or lack cilia, have laminal, perforate or eperforate apothecia, usually have simple rhizines and filiform, cylindrical, bacilliform or sublageniform conidia. It is closely related to Flavoparmelia but the status of these genera requires further investigation. Nineteen new combinations are made.

Ascomycota↗

PubMedDate not supplied

Phylogenetics and evolution of nematode-trapping fungi (Orbiliales) estimated from nuclear and protein coding genes.

The systematic classification of nematode-trapping fungi is redefined based on phylogenies inferred from sequence analyses of 28S rDNA, 5.8S rDNA and beta-tubulin genes. Molecular data were analyzed with maximum parsimony, maximum likelihood and Bayesian analysis. An emended generic concept of nematode-trapping fungi is provided. Arthrobotrys is characterized by adhesive networks, Dactylellina by adhesive knobs, and Drechslerella by constricting-rings. Phylogenetic placement of taxa characterized by stalked adhesive knobs and non-constricting rings also is confirmed in Dactylellina. Species that produce unstalked adhesive knobs that grow out to form loops are transferred from Gamsylella to Dactylellina, and those that produce unstalked adhesive knobs that grow out to form networks are transferred from Gamsylella to Arthrobotrys. Gamsylella as currently circumscribed cannot be treated as a valid genus. A hypothesis for the evolution of trapping-devices is presented based on multiple gene data and morphological studies. Predatory and nonpredatory fungi appear to have been derived from nonpredatory members of Orbilia. The adhesive knob is considered to be the ancestral type of trapping device from which constricting rings and networks were derived via two pathways. In the first pathway adhesive knobs retained their adhesive material forming simple two-dimension networks, eventually forming complex three-dimension networks. In the second pathway adhesive knobs lost their adhesive materials, with their ends meeting to form nonconstricting rings and they in turn formed constricting rings with three inflated-cells.

Animals↗

PubMedDate not supplied

Molecular systematics of Helicoma, Helicomyces and Helicosporium and their teleomorphs inferred from rDNA sequences.

Three genera of asexual, helical-spored fungi, Helicoma, Helicomyces and Helicosporium traditionally have been differentiated by the morphology of their conidia and conidiophores. In this paper we assessed their phylogenetic relationships from ribosomal sequences from ITS, 5.8S and partial LSU regions using maximum parsimony, maximum likelihood and Bayesian analysis. Forty-five isolates from the three genera were closely related and were within the teleomorphic genus Tubeufia sensu Barr (Tubeufiaceae, Ascomycota). Most of the species could be placed in one of the seven clades that each received 78% or greater bootstrap support. However none of the anamorphic genera were monophyletic and all but one of the clades contained species from more than one genus. The 15 isolates of Helicoma were scattered through the phylogeny and appeared in five of the clades. None of the four sections within the genus were monophyletic, although species from Helicoma sect. helicoma were concentrated in Clade A. The Helicosporium species also appeared in five clades. The four Helicomyces species were distributed among three clades. Most of the clades supported by sequence data lacked unifying morphological characters. Traditional characters such as the thickness of the conidial filament and whether conidiophores were conspicuous or reduced proved to be poor predictors of phylogenetic relationships. However some combinations of characters including conidium colour and the presence of lateral, tooth-like conidiogenous cells did appear to be predictive of genetic relationships.

Ascomycota↗

PubMed1984

Alternative referent standards for cardiac normality. Implications for diagnostic testing.

The radionuclide ventriculographic exercise response was evaluated in three patient populations representing alternative referent standards for cardiac normality: patients with normal coronary arteriograms, healthy volunteers, and uncatheterized patients with a low probability of coronary artery disease. Disease probability was determined by Bayesian analysis of age, sex, symptoms, and the results of cardiac fluoroscopy, exercise electrocardiography, or thallium scintigraphy. A wide range of ventriculographic responses was noted in the 62 catheterized normal patients; 21 (34%) had an abnormal ejection fraction response and 22 (35%) had an abnormal wall motion response. In contrast, the ejection fraction and wall motion responses were normal in the 9 volunteers. In 90 patients (18 catheterized and 72 uncatheterized) who had low disease probability (less than 1%), abnormal responses were rare; the ejection fraction response was abnormal in only 7% and the wall motion response was abnormal in 8%. Thus, these three populations are not equivalent referent standards of normality. Volunteers and patients with low disease probability provide too strict a standard, and their use can overestimate test specificity; catheterized normal patients, on the other hand, provide too lenient a standard, and their use can underestimate test specificity.

Adult↗