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Relation between wall thickening on gated perfusion SPECT and functional recovery after coronary revascularization in patients with previous myocardial infarction.

PURPOSE: This study aimed to evaluate whether wall thickening analysis by gated perfusion single-photon emission computed tomography (SPECT) is useful in predicting functional recovery after revascularization. METHODS: Forty-one patients with previous myocardial infarction and left ventricular (LV) dysfunction (ejection fraction, EF, 36+/-6%) who were scheduled for revascularization underwent rest 99mTc-sestamibi gated SPECT. RESULTS: Of 131 akinetic or dyskinetic segments at baseline echocardiography, 82 (63%) recovered after revascularization. Compared with wall thickening analysis, perfusion imaging provided higher sensitivity (78% vs 50%, P<0.0001) and specificity (80% vs 71%, P<0.0005). Among segments with > or =55% sestamibi uptake (viable), those with detectable wall thickening had a higher likelihood of functional recovery than those with absent wall thickening (95% vs 77%, P<0.05). In segments with improved function, the absence of wall thickening was associated with lower sestamibi activity than was observed when detectable wall thickening was present (58+/-14% vs 71+/-13%, P<0.0005). An increase in EF of > or =5% was detectable in 22 (54%) patients. For the prediction of EF improvement, perfusion imaging provided a higher sensitivity than wall thickening analysis (68% vs 41%, P<0.05), while specificity was not significantly different (68% vs 74%). The prevalence of patients with functional recovery did not change when wall thickening analysis was considered in addition to perfusion status (73% in patients with detectable wall thickening and 70% in those without; P=NS). CONCLUSION: In patients with coronary artery disease, wall thickening analysis by gated perfusion SPECT provides additional information compared with perfusion data for the prediction of segmental functional recovery. However, on a patient basis, wall thickening assessment seems to be of more limited value than perfusion status.

Adult↗

A distribution for multivariate frailty based on the compound Poisson distribution with random scale.

Frailty models are often used to model heterogeneity in survival analysis. The most common frailty model has an individual intensity which is a product of a random factor and a basic intensity common to all individuals. This paper uses the compound Poisson distribution as the random factor. It allows some individuals to be non-susceptible, which can be useful in many settings. In some diseases, one may suppose that a number of families have an increased susceptibility due to genetic circumstances. Then, it is logical to use a frailty model where the individuals within each family have some shared factor, while individuals between families have different factors. This can be attained by randomizing the Poisson parameter in the compound Poisson distribution. To our knowledge, this is a new distribution. The power variance function distributions are used for the Poisson parameter. The subsequent appearing distributions are studied in some detail, both regarding appearance and various statistical properties. An application to infant mortality data from the Medical Birth Registry of Norway is included, where the model is compared to more traditional shared frailty models.

Humans↗

Rasch analysis of the Gross Motor Function Measure: validating the assumptions of the Rasch model to create an interval-level measure.

OBJECTIVES: To describe the Rasch analysis of the Gross Motor Function Measure (GMFM-88) and to demonstrate how the assumptions of unidimensionality, sample-free measurement, and test-free measurement were validated to create an interval level measure. DESIGN: Cross-sectional and longitudinal (12-mo) data from a prospective study of motor development in children with cerebral palsy (CP) were used for the analysis. SETTING: Motor assessments were completed at 18 children's ambulatory rehabilitation centers in Ontario, Canada, by pediatric physical therapists trained in the use of the GMFM-88. PARTICIPANTS: The first 537 of 682 children enrolled into a longitudinal study of motor development in children with CP. Children had a mean age of 6.43+/-2.75 years (range, 11mo-12y) with varying types and severity of CP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The GMFM-88. RESULTS: The Rasch analysis, in conjunction with clinical decisions, identified 66 items from the GMFM-88 that formed a unidimensional measure (GMFM-66). Assumptions of sample-free and test-free measurement were confirmed, and a user-friendly scoring program was developed. CONCLUSIONS: The GMFM-66 is an interval-level measure of gross motor function for children with CP; it should improve the scoring, interpretation, and overall clinical and research utility over the original GMFM.

Algorithms↗

Evolution of the RNA polymerase II C-terminal domain.

In recent years a great deal of biochemical and genetic research has focused on the C-terminal domain (CTD) of the largest subunit (RPB1) of DNA-dependent RNA polymerase II. This strongly conserved domain of tandemly repeated heptapeptides has been linked functionally to important steps in the initiation and processing of mRNA transcripts in both animals and fungi. Although they are absolutely required for viability in these organisms, C-terminal tandem repeats do not occur in RPB1 sequences from diverse eukaryotic taxa. Here we present phylogenetic analyses of RPB1 sequences showing that canonical CTD heptads are strongly conserved in only a subset of eukaryotic groups, all apparently descended from a single common ancestor. Moreover, eukaryotic groups in which the most complex patterns of ontogenetic development occur are descended from this CTD-containing ancestor. Consistent with the results of genetic and biochemical investigations of CTD function, these analyses suggest that the enhanced control over RNA polymerase II transcription conveyed by acquired CTD/protein interactions was an important step in the evolution of intricate patterns of gene expression that are a hallmark of large, developmentally complex eukaryotic organisms.

Amino Acid Motifs↗

Type 2 tasks in the theory of signal detectability: discrimination between correct and incorrect decisions.

It has been known for over 40 years that there are two fundamentally different kinds of detection tasks in the theory of signal detectability. The Type 1 task is to distinguish between events defined independently of the observer; the Type 2 task is to distinguish between one's own correct and incorrect decisions about those Type 1 events. For the Type 1 task, the behavior of the detector can be summarized by the traditional receiver operating characteristic (ROC) curve. This curve can be compared with a theoretical ROC curve, which can be generated from overlapping probability functions conditional on the Type 1 events on an appropriate decision axis. We show how to derive the probability functions underlying Type 2 decisions from those for the Type 1 task. ROC curves and the usual measures of performance are readily obtained from those Type 2 functions, and some relationships among various Type 1 and Type 2 performance measures are presented. We discuss the relationship between Type 1 and Type 2 confidence ratings and caution against the practice of presenting transformed Type 2 ratings as empirical Type 1 ratings.

Cues↗

Using comparative genomic data to test for fast-X evolution.

Genes may acquire nonsynonymous substitutions more rapidly when X-linked than when autosomal, but evidence for "fast-X evolution" has been elusive. Fast-X evolution could explain the disproportionate contribution of X-linked genes to hybrid sterility and other traits. Here, we use a comparative genomic approach, with sequences of 30-110 genes in four Drosophila species, to test for fast-X evolution. Specifically, the 3L autosome arm in D. melanogaster and D. simulans is homologous to the right arm of the X chromosome in D. pseudoobscura and D. miranda. We executed two paired comparisons to determine how often genes on this chromosome arm exhibit higher rates of nonsynonymous substitution in the D. pseudoobscura species group, as predicted by fast-X evolution. We found a statistically significant pattern consistent with fast-X evolution in one comparison and a similar trend in the other comparison. Variation in functional constraints across genes may have masked the signature of fast-X evolution in some previous studies, and we conclude paired comparisons are more powerful for examining rates of evolution of genes when X-linked over autosomal.

Animals↗

The ex-Wald distribution as a descriptive model of response times.

We propose a new quantitative model of response times (RTs) that combines some advantages of substantive, process-oriented models and descriptive, statistically oriented accounts. The ex-Wald model assumes that RT may be represented as a convolution of an exponential and a Wald-distributed random variable. The model accounts well for the skew, shape, and hazard function of typical RT distributions. The model is based on two broad information-processing concepts: (1) a data-driven processing rate describing the speed of information accumulation, and (2) strategic response criterion setting. These concepts allow for principled expectations about how experimental factors such as stimulus saliency or response probability might influence RT on a distributional level. We present a factorial experiment involving mental digit comparisons to illustrate the application of the model, and to explain how substantive hypotheses about selective factor effects can be tested via likelihood ratio tests.

Adolescent↗

Evidence-based estimates of outcome in patients irradiated for intraocular melanoma.

BACKGROUND: Melanoma of the eye is the only potentially fatal ocular malignancy in adults. Until radiation therapy gained wide acceptance in the 1980s, enucleation was the standard treatment for the tumor. Long-term results after proton beam irradiation are now available. METHODS: We developed risk score equations to estimate probabilities of the 4 principal treatment outcomes-local tumor recurrence, death from metastasis, retention of the treated eye, and vision loss-based on an analysis of 2069 patients treated with proton beam radiation for intraocular melanoma between July 10, 1975, and December 31, 1997. Median follow-up in surviving patients was 9.4 years. RESULTS: Tumor regrowth occurred in 60 patients, and 95% of tumors (95% confidence interval, 93%-96%) were controlled locally at 15 years. Risk scores were developed for the other 3 outcomes studied. Overall, the treated eye was retained by 84% of patients (95% confidence interval, 80%-87%) at 15 years. The probabilities for vision loss (visual acuity worse than 20/200) ranged from 100% to 20% at 10 years and for death from tumor metastases from 95% to 35% at 15 years, depending on the risk group. CONCLUSIONS: High-dose radiation treatment was highly effective in achieving local control of intraocular melanomas. In most cases, the eye was salvaged, and functional vision was retained in many patients. The mortality rate was high in an identifiable subset of patients who may benefit from adjuvant therapies directed at microscopic liver metastases.

Adolescent↗

Horizontal transfer of two operons coding for hydrogenases between bacteria and archaea.

Using a phylogenetic approach, we discovered three putative horizontal transfers between bacterial and archaeal species involving large clusters of genes. One transfer involves an operon of 13 genes, called mbx, which probably was transferred into the genome of Thermotoga maritima from a species belonging or close to the Pyrococcus genus. The two others implied an operon of six genes, called ech, transferred independently to the genomes of Thermoanaerobacter tengcongensis and Desulfovibrio gigas, from a species belonging or close to the Methanosarcina genus. All these transfers affected operons coding for multisubunit membrane-bound (NiFe) hydrogenases involved in the energy metabolism of the donor genomes. The functionality of the transferred operons has not been experimentally demonstrated for T. maritima, whereas in D. gigas and T. tengcongensis the encoded multisubunit hydrogenase could have a role in energy conservation. This report adds several cases of horizontal gene transfers among hydrogenases already described.

Archaea↗

Risk assessment for inpatient survival in the long-term acute care setting after prolonged critical illness.

OBJECTIVE: The past decade has witnessed growth in the long-term acute care (LTAC) hospital industry. There are no reliable risk assessment models that can adjust outcomes across such facilities with different criteria for admitting patients. Variation in reported outcomes makes it difficult to determine whether a patient, or group of patients, may benefit from such care. This study sought to determine the extent to which survival in the LTAC setting is associated with age, race, residual organ system failures (OSFs), or APACHE (acute physiology and chronic health evaluation) III scores at the time of admission to LTAC. DESIGN: Retrospective medical record review. SETTING: Four freestanding facilities of a LTAC hospital. PATIENTS: A sample of 300 hospital admissions weighted to represent the study hospital population. MEASUREMENTS: Inpatient survival modeled as a function of age, APACHE III score calculated within 72 h prior to LTAC admission, and residual OSFs present on admission to LTAC. RESULTS: Logistic regression analysis shows age and OSF were most predictive of inpatient survival (receiver operating characteristic curve area = 0.81). APACHE III score was not predictive of survival in the multivariate model. CONCLUSIONS: Survival in LTAC is primarily associated with age and OSFs, which should be used to adjust for patient populations among LTAC settings when comparing outcomes. Our model identifies a group of patients with the poorest likelihood of survival in the LTAC setting, and may be used to facilitate dialogue with patients and family in cases where continued aggressive care is least effective.

APACHE↗

Utility of the force of infection model for assessing changes in the dynamics of bancroftian filarial infections.

Force of infection is measured in terms of the number of effective contacts that have been introduced into the population by infective vectors. The utility of such a measure in describing the dynamics of bancroftian filarial infection was tested. Force of infection (beta) incorporating the durations of patent period and pre-patent period was estimated for different age classes (assuming that it is constant in that particular age class) and it was found that the predicted post-control prevalences were close to the observed figures. Utility of Remme's model in areas with different transmission levels is discussed. It was examined whether the empirical function generally used in helminth infections to describe the functional relationship between beta and age could be used for lymphatic filariasis. The relationship between the two was not adequately described by the function. Force of infection, when compared with rate of acquisition calculated using longitudinal data, showed that this measure could be used as a crude estimate of rate of acquisition in places which do not have longitudinal data sets.

Adolescent↗

Temporal bone volumetric image deblurring in spiral computed tomography scanning.

RATIONALE AND OBJECTIVES: We developed a method for volumetric image deblurring in spiral (helical) computed tomography (CT) scanning with a three-dimensional (3D) Gaussian point spread function (PSF) to improve the quality of temporal bone spiral CT images for assessing the position of cochlear implants electrodes. METHODS: A patient was scanned after cochlear implantation, and the temporal bone was reconstructed into a volume with 128 voxels per dimension, 0.1 mm per voxel side, and x 10 gray-scale expansion. The 3D PSF in spiral CT imaging was assumed to be Gaussian separable transversely and longitudinally. Standard deviations of the PSF were derived and subjectively adjusted. The image was then deconvolved using Wiener filtering and maximum-likelihood deconvolution methods. Image quality was assessed both visually and quantitatively using cross-sectional area at half of the maximum (CAHM) of the implanted array as the figure of merit. RESULTS: Substantial image deblurring was achieved via deconvolution. Subjectively, anatomic structures were more clearly shown. Deconvolution reduced the CAHM by approximately one third, on average. Three-dimensional deconvolution had better image quality than two-dimensional deconvolution. The maximum-likelihood method produced superior image quality but took longer to process relative to Wiener filtering. CONCLUSION: Volumetric image deblurring is practical with a Gaussian PSF. The maximum-likelihood method is preferred if time permits. Deconvolution facilitates the study of fine details of the temporal bone and cochlear implant.

Adult↗

Transmitting males and carrier females in fragile X--revisited.

Fragile X "transmitting males" have customarily been defined as phenotypically normal hemizygotes, who show very few or no fragile sites, and who transmit the fragile X premutation to phenotypically normal daughters. However, an objective justification of this definition was lacking. The discovery of an unstable CCG repeat as the genetic basis of fragile X further emphasized the apparent distinction between the "normal transmitting males" with short repeat and expression of the FMR1 gene, and the affected males with larger repeats (delta > 0.6 kb) and a complete lack of FMR1 transcription. We have recently shown that the transition between these two groups in phenotypic expression of fragile X is gradual, mainly on account of methylation mosaicism. However, there were insufficient data on the phenotype within the short repeat (0.0 < delta < 0.6) range. In this paper we approach this problem by comparing some clinical, anthropometric, and psychometric data from a sample of normal transmitting males with those from their non-fragile X male relatives. Moreover, female carriers with short repeat are compared for the same traits with their non-fragile X female relatives. The results have shown that both males and females with a short repeat differed significantly from normal on several psychometric and physical measurements, and males only showed differences in typical facial traits. Further studies of genotype-phenotype correlations within the short repeat range, including the estimate of FMR1 gene function and a more exact estimate of repeat size, is required before genetic explanation for the clinical findings can be provided.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Correlated evolutionary divergence of egg size and a mitochondrial protein across the Isthmus of Panama.

An explicit assumption of studies that employ a mitochondrial DNA (mtDNA) molecular clock is that mtDNA evolves independently of morphology. Here we report a very strong correlation between egg size divergence and cytochrome c oxidase-1 (CO1) amino acid sequence divergence among sister species of bivalve molluscs separated by the Central American Isthmus (i.e., "geminate" species). Analyses of the molecular data reveal that CO1 sequences likely did not diverge as a function of time or evolve in response to positive natural selection. Given that an excess of CO1 amino acid polymorphism exists within species (as expected if most mutations are only slightly deleterious), a third hypothesis is that reductions in effective population size could simultaneously increase the fixation rate of nearly neutral mtDNA polymorphisms and in some way also facilitate egg size evolution. The remarkable strength of the relationship between egg size and CO1 amino acid sequence demonstrates that, even in the absence of an obvious functional relationship or clock-like evolution, the amounts of molecular and morphological change can be tightly correlated, and therefore may reflect common processes. Accordingly, the assumption that the evolutionary divergence of molecules and morphology are independent must always be carefully examined.

Animals↗

Decline in lung function in the Busselton Health Study: the effects of asthma and cigarette smoking.

Asthma in adults may be associated with chronic airflow obstruction, possibly resulting from airway disease in early life and/or a greater rate of decline in lung function in adult life compared with those with asthma. Treatment and cigarette smoking may also influence the rate of decline of lung function. The aim of this analysis was to examine the level and rate of decline in lung function in relationship to asthma and cigarette smoking in adults. Subjects (n = 9,317) had participated as adults (> 18 years) in one or more of the cross-sectional Busselton Health Surveys between 1966 and 1981 or in the follow-up study of 1994/1995. The effects of sex, doctor-diagnosed asthma, smoking status, and anthropometric data on the level and rate of decline in FEV1 were examined in a linear mixed effects model. At the age of 19 years, FEV1 was reduced in subjects with asthma but was similar in smokers and nonsmokers. Males, taller subjects, smokers, and subjects with asthma had greater declines in FEV1 with age. Smoking and asthma had additive but not multiplicative effects on decline. Thus, asthma is associated with reduced lung function at the beginning of adult life as well as an increased rate of decline during adult life.

Adult↗

Cross genome phylogenetic analysis of human and Drosophila G protein-coupled receptors: application to functional annotation of orphan receptors.

BACKGROUND: The cell-membrane G-protein coupled receptors (GPCRs) are one of the largest known superfamilies and are the main focus of intense pharmaceutical research due to their key role in cell physiology and disease. A large number of putative GPCRs are 'orphans' with no identified natural ligands. The first step in understanding the function of orphan GPCRs is to identify their ligands. Phylogenetic clustering methods were used to elucidate the chemical nature of receptor ligands, which led to the identification of natural ligands for many orphan receptors. We have clustered human and Drosophila receptors with known ligands and orphans through cross genome phylogenetic analysis and hypothesized higher relationship of co-clustered members that would ease ligand identification, as related receptors share ligands with similar structure or class. RESULTS: Cross-genome phylogenetic analyses were performed to identify eight major groups of GPCRs dividing them into 32 clusters of 371 human and 113 Drosophila proteins (excluding olfactory, taste and gustatory receptors) and reveal unexpected levels of evolutionary conservation across human and Drosophila GPCRs. We also observe that members of human chemokine receptors, involved in immune response, and most of nucleotide-lipid receptors (except opsins) do not have counterparts in Drosophila. Similarly, a group of Drosophila GPCRs (methuselah receptors), associated in aging, is not present in humans. CONCLUSION: Our analysis suggests ligand class association to 52 unknown Drosophila receptors and 95 unknown human GPCRs. A higher level of phylogenetic organization was revealed in which clusters with common domain architecture or cellular localization or ligand structure or chemistry or a shared function are evident across human and Drosophila genomes. Such analyses will prove valuable for identifying the natural ligands of Drosophila and human orphan receptors that can lead to a better understanding of physiological and pathological roles of these receptors.

Amino Acid Sequence↗

Comprehensive analysis and prediction of synthetic lethality using subcellular locations.

The lethality of a gene is a fundamental and representative measure for understanding the function of a gene and its associated bio-systems. Recently, many research groups have started focusing on the concept of synthetic lethality. The synthetic lethality between genes is defined by the combination of mutations in two genes causing cell death. Here, we confirm that synthetic lethality and cellular location have close relationships among the Saccharomyces cerevisiae genes. Furthermore, we attempt the prediction of candidate gene pairs with synthetic lethality. The prediction is based on the hierarchical aspect model (HAM) which learns from a data set of cellular location to estimate a likelihood value indicating the synthetic lethality between genes.

Cell Death↗

Analysis of forkhead and snail expression reveals epithelial-mesenchymal transitions during embryonic and larval development of Nematostella vectensis.

The winged helix transcription factor Forkhead and the zinc finger transcription factor Snail are crucially involved in germ layer formation in Bilateria. Here, we isolated and characterized a homolog of forkhead/HNF3 (FoxA/group 1) and of snail from a diploblast, the sea anemone Nematostella vectensis. We show that Nematostella forkhead expression starts during late Blastula stage in a ring of cells that demarcate the blastopore margin during early gastrulation, thereby marking the boundary between ectodermal and endodermal tissue. snail, by contrast, is expressed in a complementary pattern in the center of forkhead-expressing cells marking the presumptive endodermal cells fated to ingress during gastrulation. In a significant portion of early gastrulating embryos, forkhead is expressed asymmetrically around the blastopore. While snail-expressing cells form the endodermal cell mass, forkhead marks the pharynx anlage throughout embryonic and larval development. In the primary polyp, forkhead remains expressed in the pharynx. The detailed analysis of forkhead and snail expression during Nematostella embryonic and larval development further suggests that endoderm formation results from epithelial invagination, mesenchymal immigration, and reorganization of the endodermal epithelial layer, that is, by epithelial-mesenchymal transitions (EMT) in combination with extensive morphogenetic movements. snail also governs EMT at different processes during embryonic development in Bilateria. Our data indicate that the function of snail in Diploblasts is to regulate motility and cell adhesion, supporting that the triggering of changes in cell behavior is the ancestral role of snail in Metazoa.

Amino Acid Sequence↗