Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “variational inference”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed1995

Genetic characterization of isolates of Giardia duodenalis by enzyme electrophoresis: implications for reproductive biology, population structure, taxonomy, and epidemiology.

The nature and extent of genetic variation in Giardia was used to infer its mode of reproduction, population structure, taxonomy, and zoonotic potential. Ninety-seven isolates of Giardia duodenalis, from a defined area in Western Australia and throughout Australia and overseas, were obtained from humans, cats, cattle, sheep, dogs, goat, beaver, and rats. Enzyme electrophoresis revealed extensive genetic variation with 47 different zymodemes. The widespread occurrence of certain zymodemes and the similarity of relationships among isolates inferred from independent genetic markers suggests a clonal population structure for G. duodenalis, although occasional bouts of genetic exchange may occur. The 47 zymodemes clustered similarly in phenetic (UPGMA) and phylogenetic (Fitch-Margoliash) analyses. The level of genetic diversity in isolates from a defined geographical area in Western Australia was similar to the level of diversity in isolates from throughout Australia. These data suggest that clonal lineages within G. duodenalis are evolutionarily independent. Although there was a significant overall correlation between genetic distance separating zymodemes and occurrence in different host species, we found genetically identical isolates from humans and other animals and extensive genetic diversity between isolates from humans. We interpret this as evidence for zoonotic transmission of the parasite.

Animals↗
PubMed2005

Using multilevel models for assessing the variability of multinational resource use and cost data.

Multinational economic evaluations often calculate a single measure of cost-effectiveness using cost data pooled across several countries. To assess the validity of pooling international cost data the reasons for cost variation across countries need to be assessed. Previously, ordinary least-squares (OLS) regression models have been used to identify factors associated with variability in resource use and total costs. However, multilevel models (MLMs), which accommodate the hierarchical structure of the data, may be more appropriate. This paper compares these different techniques using a multinational dataset comprising case-mix, resource use and cost data on 1300 stroke admissions from 13 centres in 11 European countries. OLS and MLMs were used to estimate the effect of patient and centre-level covariates on the total length of hospital stay (LOS) and total cost. MLMs with normal and gamma distributions for the data within centres were compared. The results from the OLS model showed that both patient and centre-level covariates were associated with LOS and total cost. The estimates from the MLMs showed that none of the centre-level characteristics were associated with LOS, and the level of spending on health was the centre-level variable most highly associated with total cost. We conclude that using OLS models for assessing international variation can lead to incorrect inferences, and that MLMs are more appropriate for assessing why resource use and costs vary across centres.

Age Factors↗
PubMed2004

Influence of oscillatory mixing on the injectability of three acrylic and two calcium-phosphate bone cements for vertebroplasty.

Injecting acrylic and, increasingly, calcium-phosphate cements into the porous bone structure is an emerging procedure, referred to as vertebroplasty, for the augmentation of osteoporotic vertebrae. Despite the benefits of vertebroplasty, it has limitations. The limitations of interest in this study are the injectability of bone cements and their mixing variability (i.e., low reproducibility of resulting viscosity). The objective of this study is to investigate the effect of oscillatory versus manual mixing on cement viscosity and mixing variability. Five cements are tested: (a) Vertebroplastic, (b) DP-Pour, (c) Antibiotic Simplex, (d) chronOS Inject, and (e) Biopex. Compared to manual mixing, oscillatory mixing significantly decreased the mean viscosity and the mixing variability, which was inferred from the coefficient of variation. For example, under oscillatory mixing, the viscosity and the variability for Vertebroplastic decreased to one-third of the corresponding values for manual mixing. Similar results were obtained for the other cements. The decrease in viscosity is attributed to the pseudo-plastic behavior of bone cements. The decrease in the variability of cement viscosity was attributed to greater dispersive mixing of the cement components under oscillatory mixing. The decrease in viscosity eases the injection by reducing the pressure required. The decrease in the variability of cement viscosity increases reproducibility of the cement injection. Oscillatory mixing appears to have the potential to contribute to improving vertebroplasty.

Bone Substitutes↗
PubMed1980

Turner syndrome patients are H-Y positive.

H-Y antigen was examined in six patients exhibiting the characteristic features of Turner syndrome. Five of the patients were of the karyotype 45,X, and one was a mosaic 45,X/46, Xi(Xq). H-Y antigen was detected in all of them, however, compared to male controls, their antigen titer was reduced. Within the intermediate range between female and male controls, considerable interindividual variation was detected among the patients which could be due to least in part to biological variation. The findings permit the inference that the H-Y structural gene is not Y-linked, and support the assumptions of an X-linked gene escaping inactivation and of it controlling the expression of the H-Y structural gene. It is probable that the structural gene itself is autosomal. The results also suggest that male gonadal differentiation is dependent on a threshold level of H-Y antigen concentration.

Cytotoxicity Tests, Immunologic↗
PubMed1995

Probing the evolution of senescence in Drosophila melanogaster with P-element tagging.

Natural populations host a wealth of genetic variation in longevity and age-specific schedules of reproduction. This variation provides critical information for inferring the evolutionary origin of senescence. Patterns of mutational effects on age-specific fecundity and survival provide additional insight to distinguish alternative models of senescence. In this study, P-elements bearing the white minigene were inserted at random into a common genetic background, generating lines of D. melanogaster with single, stable transposon inserts. A series of 48 single-P-element lines revealed statistically significant heterogeneity in both longevity and fecundity. Longevity and early fecundity were only weakly positively correlated (r = 0.286, P = 0.0398). Both the pooled sample and 30 of the individual lines exhibited a leveling of age-specific mortality at advanced ages, in opposition to the classical demographic models. To the extent that these mutational effects are representative of naturally-occurring mutations in heterogeneous populations, this result presents a problem for the evolutionary theory of senescence. Natural selection is inefficient at removing deleterious mutations that are expressed only at late ages, and selection may not differentiate between mutations whose effects on longevity are post-reproductive. A leveling of the mortality rate would also be seen if mutations whose expression is delayed until very late simply do not occur. A simulation of mutation-selection balance among the 48 P-element tagged lines shows that the mean longevity declines monotonically with increasing mutation rate, consistent with the mutation-accumulation model.

Aging↗
PubMed2004

Comparative genetics of functional trinucleotide tandem repeats in humans and apes.

Several human neurodegenerative disorders are caused by the expansion of polymorphic trinucleotide repeat regions. Many of these loci are functional short tandem repeats (STRs) located in brain-expressed genes, and their study is thus relevant from both a medical and an evolutionary point of view. The aims of our study are to infer the comparative pattern of variation and evolution of this set of loci in order to show species-specific features in this group of STRs and on their potential for expansion (therefore, an insight into evolutionary medicine) and to unravel whether any human-specific feature may be identified in brain-expressed genes involved in human disease. We analyzed the variability of the normal range of seven expanding STR CAG/CTG loci (SCA1, SCA2, SCA3-MJD, SCA6, SCA8, SCA12, and DRPLA) and two nonexpanding polymorphic CAG loci (KCNN3 and NCOA3) in humans, chimpanzees, gorillas, and orangutans. The study showed a general conservation of the repetitive tract and of the polymorphism in the four species and high heterogeneity among loci distributions. Humans present slightly larger alleles than the rest of species but a more relevant difference appears in variability levels: Humans are the species with the largest variance, although only for the expanding loci, suggesting a relationship between variability levels and expansion potential. The sequence analysis shows high levels of sequence conservation among species, a lack of correspondence between interruption patterns and variability levels, and signs of conservative selective pressure for some of the STR loci. Only two loci (SCA1 and SCA8) show a human specific distribution, with larger alleles than the rest of species. This could account, at the same time, for a human-specific trait and a predisposition to disease through expansion.

Analysis of Variance↗
PubMed2005

Scaling up population dynamics: integrating theory and data.

How to scale up from local-scale interactions to regional-scale dynamics is a critical issue in field ecology. We show how to implement a systematic approach to the problem of scaling up, using scale transition theory. Scale transition theory shows that dynamics on larger spatial scales differ from predictions based on the local dynamics alone because of an interaction between local-scale nonlinear dynamics and spatial variation in density or the environment. Based on this theory, a systematic approach to scaling up has four steps: (1) derive a model to translate the effects of local dynamics to the regional scale, and to identify key interactions between nonlinearity and spatial variation, (2) measure local-scale model parameters to determine nonlinearities at local scales, (3) measure spatial variation, and (4) combine nonlinearity and variation measures to obtain the scale transition. We illustrate the approach, with an example from benthic stream ecology of caddisflies living in riffles. By sampling from a simulated system, we show how collecting the appropriate data at local (riffle) scales to measure nonlinearities, combined with measures of spatial variation, leads to the correct inference for dynamics at the larger scale of the stream. The approach provides a way to investigate the mechanisms and consequences of changes in population dynamics with spatial scale using a relatively small amount of field data.

Animals↗
PubMed2005

The eyes of a patrolling butterfly: visual field and eye structure in the Orange Sulphur, Colias eurytheme (Lepidoptera, Pieridae).

Sensory information plays a critical role in determining an animal's behavior on both proximate and evolutionary timescales. Butterflies, like many other insects, use vision extensively over their lifetimes, and yet relatively little work has been published to date on their visual capabilities. We describe the visual system of a pierid butterfly, Colias eurytheme, with the ultimate goal of better understanding its role in shaping the behavior of this animal. We made several measurements: visual field dimensions, eye surface area, interommatidial angle (Deltaphi), facet diameter (D), and eye parameter (p). C. eurytheme had a large visual field and considerable regional variation in visual acuity, as inferred by Deltaphi and D. When compared to females, males had larger eye surface areas, smaller Deltaphi, and larger D in all regions except ventrally. Both sexes had proportionally large eye surface areas compared to other butterflies. Minimum p in males was small, indicating that some regions of their eyes may operate close to the diffraction limit. Finally, we found that both eye surface area and D scaled positively, but with negative allometry to body size. We discuss the relevance of these visual characteristics to the biology and behavior of C. eurytheme.

Animals↗
PubMed2025

Macrolide-resistant Mycoplasma pneumoniae resurgence in Chinese children in 2023: a longitudinal, cross-sectional, genomic epidemiology study.

BACKGROUND: After a prolonged period of low detection rates, Mycoplasma pneumoniae resurged in China, during September to November, 2023, raising global concern. This study aims to gain a better understanding of the genetic mechanisms underlying the 2023 increase in cases and the evolutionary dynamics of the epidemic populations, which has been previously hampered due to limited genomic data of this pathogen. METHODS: We sequenced 685 M pneumoniae isolates, including 248 isolates from 11 Chinese provinces and municipalities in 2023 and 437 isolates from Beijing (2013-22). By analysing these isolates and 436 publicly global sequences, we reconstructed the pathogen's evolutionary history using time-calibrated phylogenies and effective population size inference. We investigated potential genomic variations contributing to the 2023 resurgence through genome-wide association study and conducted phylogeographic analysis of the 2023 isolates across China. FINDINGS: Two macrolide-resistant epidemic clusters (T1-2-EC1 and T2-2-EC2) were responsible for the 2023 resurgence in China. Both clusters, having acquired the 23S ribosomal RNA A2063G mutation conferring macrolide resistance, emerged in approximately 1997 and 2014, respectively, and subsequently outcompeted their predecessor populations. This coincided with China's large-scale adoption of azithromycin for paediatric community-acquired pneumonia around the early 2000s. Aside from macrolide resistance, T1-2-EC1 independently acquired 17 clade-specific mutations and T2-2-EC2 four clade-specific mutations, which could further explain their increased competitiveness. Whole-genome analysis revealed no resurgence-specific mutations in the 2023 isolates. Phylogeographic analysis showed rapid mixing of T1-2-EC1 isolates between different sampled regions within China. INTERPRETATION: Our study provides evidence that the 2023 resurgence in China is a continuation of the pre-COVID epidemic, rather than emergence of novel variants. The high prevalence of macrolide resistance and rapid intranational spread emphasise the urgent need for enhanced global surveillance of this pathogen. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China for Key Programs of China Grants, and Beijing High-Level Public Health Technical Talent Project.

Humans↗
PubMed1999

Risk adjustment for interhospital comparison of primary cesarean rates.

OBJECTIVE: To create a method of controlling for case mix so that inferences could be made about variation in cesarean rates among hospitals. METHODS: A total of 160,753 births from 1991 Illinois birth certificate data were analyzed. A multivariate model of characteristics independently associated with cesarean delivery was developed from a random 25% sample, validated on the other 75%, and used to create a probability of cesarean delivery for each woman. The validated model was used to calculate a predicted primary cesarean delivery rate for the 154 hospitals in Illinois that did at least 100 deliveries per year. RESULTS: The final model included both medical and sociodemographic risk factors and predicted primary cesarean rates accurately over a full range of rates. Thirty-five hospitals (23%) had actual rates that were higher than their individual predicted 95% confidence interval (CI). Eighty-nine hospitals (58%) had actual rates within predicted CIs. Thirty hospitals (20%) had actual rates that were lower than the predicted 95% CI. Twenty-three percent of hospitals with actual rates greater than predicted rates were not in the top quartile of actual rates. Twenty-seven percent of hospitals with actual rates in the top quartile were doing cesarean deliveries appropriate for the risk status of the population served. CONCLUSION: Risk adjusting for hospital case mix more accurately identifies outlier hospitals than raw, unadjusted primary cesarean delivery rates. We believe that risk adjusting should be the first step in understanding variations in primary cesarean delivery rates.

Adult↗
PubMedDate not supplied

Kinetic studies of the reaction of hydroxyl radicals with trichloroethylene and tetrachloroethylene.

Rate coefficients are reported for the gas-phase reaction of the hydroxyl radical (OH) with C2HCl3 (k(1)) and C2Cl4 (k2) over an extended temperature range at 740+/-10 Torr in a He bath gas. These absolute rate measurements were accomplished using a laser photolysis/laser-induced fluorescence (LP/LIF) technique under slow flow conditions. The simple Arrhenius equation adequately describes the low temperature data for k1 (<650 K) and the entire data set for k2 and is given by (in units of cm3 molecule(-1) s(-1)): k1(291 - 650 K) = (9.73+/-1.15) x 10(-13) exp (158.7+/-44.0)/T, k2(293 - 720 K ) = (1.53+/-0.14) x 10(-12) exp (-688.2+/-67.5)/T. Error limits are 2sigma values. The room temperature values for k1 and k2 are within +/-2sigma of previous data using different techniques. The Arrhenius activation energies for k1 and k2 are a factor of 2-3 lower than previously reported values. The experimental measurements for both k1 and k2 in conjunction with transition state and variation transition state theory calculations infer an OH addition mechanism. The lack of a measurable kinetic isotope effect for k1 is consistent with this mechanism. Insight into the subsequent reactions of the chemically activated intermediate are presented in the form of potential energy diagrams derived from ab initio calculations.

Journal Article↗
PubMed1990

A photochemical method to map ethidium bromide binding sites on DNA: application to a bent DNA fragment.

It is shown that, when irradiated in the visible, ethidium bromide (EB) engages in direct photochemistry with its DNA binding site. At the photochemical end point, an average of one single-strand break is produced per bound EB molecule in a reaction which also bleaches the dye chromophore. Using high-resolution electrophoresis, we have mapped the distribution of EB photocleavage sites on DNA, at one-base resolution. It is argued that because the photocleavage is stoichiometric, the resulting pattern is similar to, if not identical with, the local distribution of EB binding affinity. When interpreted in the context of the extensive thermodynamic and structural data which are available for EB, a binding distribution of that kind can be used to infer details of DNA structure variation within the underlying helix. As a first application of the method, we have used EB to probe the structure of a 265 bp fragment of DNA, which had been described as being bent as the result of a periodic array of oligo(A) segments [Kitchin et al. (1986) J. Biol. Chem. 261, 11302]. The EB mapping data provide evidence that the oligo(A) elements in this fragment assume a local secondary structure which is different than that assumed by isolated ApA nearest neighbors and that the ends of the oligo(A) elements comprise a junctional domain with EB binding properties which differ from those of the oligo(A) element or of random-sequence DNA.

Adenine Nucleotides↗
PubMed2000

Factors associated with thoracic spinal cord injury, lesion level and rotator cuff disorders.

BACKGROUND: The study was concerned with the secondary functional compromise persons with long-term paraplegia contend with, that has been shown to be associated with wheelchair use. Of particular interest was the relationship between the level of thoracic spinal cord injury (SCI) and factors predisposing to rotator cuff disorders (RCD), one of the most common upper extremity musculoskeletal complications linked with long-term SCI. Disorders of these peri-articular structures have previously been associated with impaired trunk postural control and abnormal muscle strength ratios in both able-bodied groups and in paraplegic athletes. Despite their neurologically intact shoulder joint musculature, high-level and low-level paraplegics have different degrees of trunk and pelvic stability available to them during activities of daily living (ADL). This fundamental functional anatomical difference between high-level and low-level paraplegics had not previously been related to the diagnosis of RCD in a non-athletic long-term paraplegic population. METHODS: A descriptive cross sectional study was undertaken to demonstrate the differences in the prevalence of clinically diagnosed RCD in a high-level (n=22) and a low-level (n=20) group of persons with long-term paraplegia. Any perceived differences were then related to the functional anatomical variations between the two groups. Inferences were made based on factors predisposing to RCD known to exist among both able-bodied and paraplegic athletes. The 42 subjects completed the Wheelchair User's Shoulder Pain Index (WUSPI) to establish the presence or absence of shoulder pain and the Musculoskeletal Function Assessment (MFA) instrument to determine differences in functional ability and perceived degree of difficulty within five categories of ADL. Each participant underwent a clinical examination using validated provocative clinical tests and isometric muscle strength ratio testing. RESULTS: There was a higher prevalence of RCD in the high-level group (P=0.009) which correlated with decreased trunk control (P=0.009). Differences in ability to perform functional tasks were not shown to be greater in the high-level group, although there was a higher degree of perceived difficulty in ADL. Muscle strength imbalances between the shoulder adductors and abductors were shown to be greater in the high-level group. CONCLUSIONS: The results of this study suggest that the functional anatomical differences that exist within paraplegia contribute to the propensity of high-level paraplegic persons to suffer from RCD. These findings send a clear message to service-providers that greater acknowledgement of the differences in trunk postural control specific to the level of thoracic SCI is required. This may have implications for the prescription of wheelchairs, assistive devices and instruction for alternative ADL techniques to this specific population.

Adult↗
PubMed1986

The ciliate Euplotes raikovi heterozygous at the mat genetic locus coreleases two individual species of mating pheromone: Genetic and biochemical evidence.

Euplotes raikovi of the wild-type strain 13 was found to be heterozygous (mat-1/mat-2) for the genetic locus mat, which is supposed to control the mating-type specificity of freely released mating pheromones ("euplomones"), and capable of yielding the two types of corresponding homozygotes (mat-1/mat-1, mat-2/mat-2). The results of euplomone purification, performed in parallel on Euplotes of the three different genotypes, showed that the heterozygous cells corelease two mat-specific euplomones (namely, euplomone r 1 associated with mat-1 and euplomone r 2 associated with mat-2), while the homozygous cells release either one of the two types according to their genotype. The two euplomones coreleased by the mat heterozygous cells were resolved as separate molecular species present in different relative amounts (euplomone r 1, approximately 70%; euplomone r 2, approximately 30%). A closely similar degree of eccentricity in the euplomone r 1/euplomone r 2 production was again found between the two homozygous cell types. It was concluded that the alleles mat-1 and mat-2 exhibit a relationship of nondominance: the heterozygote apparently behaves as the simple combination of the two corresponding homozygotes. It was inferred that the observed quantitative variations in the production of the different euplomones may be the result of a differential mat gene-type amplification occurring during the development of the cell somatic macronucleus.

Journal Article↗
PubMed1999

Inferring the fitness effects of DNA mutations from polymorphism and divergence data: statistical power to detect directional selection under stationarity and free recombination.

The fitness effects of classes of DNA mutations can be inferred from patterns of nucleotide variation. A number of studies have attributed differences in levels of polymorphism and divergence between silent and replacement mutations to the action of natural selection. Here, I investigate the statistical power to detect directional selection through contrasts of DNA variation among functional categories of mutations. A variety of statistical approaches are applied to DNA data simulated under Sawyer and Hartl's Poisson random field model. Under assumptions of free recombination and stationarity, comparisons that include both the frequency distributions of mutations segregating within populations and the numbers of mutations fixed between populations have substantial power to detect even very weak selection. Frequency distribution and divergence tests are applied to silent and replacement mutations among five alleles of each of eight Drosophila simulans genes. Putatively "preferred" silent mutations segregate at higher frequencies and are more often fixed between species than "unpreferred" silent changes, suggesting fitness differences among synonymous codons. Amino acid changes tend to be either rare polymorphisms or fixed differences, consistent with a combination of deleterious and adaptive protein evolution. In these data, a substantial fraction of both silent and replacement DNA mutations appear to affect fitness.

Adaptation, Biological↗
PubMed2026

Identification and masking of artifactual and misleading within-host variants in deep-sequencing SARS-CoV-2 data.

Deep-sequencing data are increasingly used to study within-host viral diversity and to inform evolutionary inference. For SARS-CoV-2, analyses based on intra-host single-nucleotide variants (iSNVs) have been widely applied to quantify within-host diversity and infer transmission dynamics. However, these applications critically depend on the reliable identification of low-frequency variants, which remain vulnerable to systematic and technical artifacts. In this study, we show that recurrent artifactual iSNVs are common in large-scale SARS-CoV-2 sequencing data and can persist even under conservative minor allele frequency thresholds. Using data from the UK's Office for National Statistics COVID-19 Infection Survey, we demonstrate that such artifacts are predominantly sequencing center-specific rather than primer-specific. Each center exhibits a modest, distinct set of recurrent artifactual variants showing little overlap with sites routinely masked at the consensus level. To address this, we developed a systematic, dataset-aware framework that uses recurrence within sequencing datasets to identify small, noise-adapted sets of artifactual iSNVs to mask. Applying this framework reduces spurious sharing of low-frequency variants between samples and qualitatively alters downstream inferences, including estimates of within-host diversity and transmission bottleneck sizes. Although this study focused on SARS-CoV-2, it is likely that recurrent artifactual iSNVs will be problematic for other viruses as mass-sequencing becomes increasingly routine. Together, these findings highlight the importance of explicit, dataset-aware artifact control for robust inference from within-host variation, particularly as genomic studies increasingly seek to exploit sub-consensus diversity in rapidly evolving pathogens.

Humans↗
PubMed1990

The similarity index and DNA fingerprinting.

DNA-fingerprint similarity is being used increasingly to make inferences about levels of genetic variation within and between natural populations. It is shown that the similarity index--the average fraction of shared restriction fragments--provides upwardly biased estimates of population homozygosity but nearly unbiased estimates of the average identity-in-state for random pairs of individuals. A method is suggested for partitioning the DNA-fingerprint dissimilarity into within- and between-population components. Some simple expressions are given for the sampling variances of these estimators.

Alleles↗
PubMed2006

Statistical genetics concepts and approaches in schizophrenia and related neuropsychiatric research.

Statistical genetics is a research field that focuses on mathematical models and statistical inference methodologies that relate genetic variations (ie, naturally occurring human DNA sequence variations or "polymorphisms") to particular traits or diseases (phenotypes) usually from data collected on large samples of families or individuals. The ultimate goal of such analysis is the identification of genes and genetic variations that influence disease susceptibility. Although of extreme interest and importance, the fact that many genes and environmental factors contribute to neuropsychiatric diseases of public health importance (eg, schizophrenia, bipolar disorder, and depression) complicates relevant studies and suggests that very sophisticated mathematical and statistical modeling may be required. In addition, large-scale contemporary human DNA sequencing and related projects, such as the Human Genome Project and the International HapMap Project, as well as the development of high-throughput DNA sequencing and genotyping technologies have provided statistical geneticists with a great deal of very relevant and appropriate information and resources. Unfortunately, the use of these resources and their interpretation are not straightforward when applied to complex, multifactorial diseases such as schizophrenia. In this brief and largely nonmathematical review of the field of statistical genetics, we describe many of the main concepts, definitions, and issues that motivate contemporary research. We also provide a discussion of the most pressing contemporary problems that demand further research if progress is to be made in the identification of genes and genetic variations that predispose to complex neuropsychiatric diseases.

Chromosome Mapping↗