SEARCH · PubMed Health

Results for “Likelihood Functions”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 1,009 records · Page 56Linked to original sources

PubMed2004

Evolutionary diversity of vertebrate small heat shock proteins.

All vertebrates express multiple small heat shock proteins (sHsps), which are important components of the cellular chaperoning machinery and display a spectacular diversity of functions. This ranges from remodeling the cytoskeleton and inhibiting apoptosis to serving as structural proteins in eye lens and sperm tail. Most information is available for the 10 known mammalian sHsps, formally named HspB1-B10. Only three of them (Hsp27/B1, alphaA-crystallin/B4, alphaB-crystallin/B5) have been reported from nonmammalian vertebrates, while an apparent paralog, Hsp30/B11, is found in frogs and teleost fish. To reconstruct the evolutionary diversification of the sHsps in vertebrates, we searched for additional sHsps in genome, protein, and EST databases and sequenced some avian and amphibian sHsps (HspB2, Hsp30/B11). The urochordate Ciona intestinalis was included in the search, as the outgroup of vertebrates. Orthologs of seven mammalian sHsps were now found in other vertebrate classes. Two novel sHsps, named HspB11 and HspB12, were recognized in birds, and four novel sHsps, named HspB12-B15, in teleost fish. Secondary structure predictions of orthologous sHsps from different vertebrate classes indicate conservation of the beta-sandwich structure of the functionally important C-terminal "alpha-crystallin domain," while the N-terminal domains generally have alpha-helical structures, despite their pronounced sequence variation. The constructed chordate sHsp tree is supported by shared introns, indels, and diagnostic sequences. The tree distinguishes putative orthologous and paralogous relationships, which will facilitate the functional and structural comparison of the various vertebrate sHsps. The 15 recognized paralogous vertebrate sHsps reflect the period of extensive gene duplications early in vertebrate evolution. Eleven of these sHsps are grouped in a clade that might be specific for chordates. It is inferred that at least 13 intron insertions have occurred during the evolution of chordate sHsp genes, while a single ancient intron is maintained in some lineages, in line with the general trend of massive intron gain before or during early vertebrate radiation. Interesting is the occurrence of several head-to-head located pairs of chordate sHsp genes.

Amino Acid Sequence↗

PubMed2005

Social participation attenuates decline in perceptual speed in old and very old age.

Does an engaged and active lifestyle in old age alleviate cognitive decline, does high cognitive functioning in old age increase the possibility of maintaining an engaged and active lifestyle, or both? The authors approach this conundrum by applying a structural equation model for testing dynamic hypotheses, the dual change score model (J. J. McArdle & F. Hamagami, 2001), to 3-occasion longitudinal data from the Berlin Aging Study (Time 1: n=516, age range=70-103 years). Results reveal that within a bivariate system of perceptual speed and social participation, with age and sociobiographical status as covariates, prior scores of social participation influence subsequent changes in perceptual speed, while the opposite does not hold. Results support the hypothesis that an engaged and active lifestyle in old and very old age may alleviate decline in perceptual speed.

Aged↗

PubMed2000

Tests for gaussian repeated measures with missing data in small samples.

For small samples of Gaussian repeated measures with missing data, Barton and Cramer recommended using the EM algorithm for estimation and reducing the degrees of freedom for an analogue of Rao's F approximation to Wilks' test. Computer simulations led to the conclusion that the modified test was slightly conservative for total sample size of N=40. Here we consider additional methods and smaller sample sizes, Nin¿12,24¿. We describe analogues of the Pillai-Bartlett trace, Hotelling-Lawley trace and Geisser-Greenhouse corrected univariate tests which allow for missing data. Eleven sample size adjustments were examined which replace N by some function of the numbers of non-missing pairs of responses in computing error degrees of freedom. Overall, simulation results allowed concluding that an adjusted test can always control test size at or below the nominal rate, even with as few as 12 observations and up to 10 per cent missing data. The choice of method varies with the test statistic. Replacing N by the mean number of non-missing responses per variable works best for the Geisser-Greenhouse test. The Pillai-Bartlett test requires the stronger adjustment of replacing N by the harmonic mean number of non-missing pairs of responses. For Wilks' and Hotelling-Lawley, an even more aggressive adjustment based on the minimum number of non-missing pairs must be used.

Choline↗

PubMed2003

Age and National Institutes of Health Stroke Scale Score within 6 hours after onset are accurate predictors of outcome after cerebral ischemia: development and external validation of prognostic models.

BACKGROUND AND PURPOSE: To date, no validated, comprehensive, and practicable model exists to predict functional recovery within the first hours of cerebral ischemic symptoms. The purpose of this study was to externally validate 2 prognostic models predicting functional outcome and survival at 100 days within the first 6 hours after onset of acute cerebral ischemia. METHODS: On admission to a participating hospital, patients were registered prospectively and included according to defined criteria. Follow-up was performed 100 days after the event. With the use of prospectively collected data, 2 prognostic models were developed and internally calibrated in 1079 patients and externally validated in 1307 patients. By means of age and National Institutes of Health Stroke Scale (NIHSS) score as independent variables, model I predicts incomplete functional recovery (Barthel Index <95) versus complete functional recovery, and model II predicts mortality versus survival. RESULTS: In the validation data set, model I correctly predicted 62.9% of the patients who were incompletely restituted or had died and 83.2% of the completely restituted patients, and model II correctly predicted 57.9% of the patients who had died and 91.5% of the surviving patients. Both models performed better than the treating physicians' predictions made within 6 hours after admission. CONCLUSIONS: The resulting prognostic models are useful to correctly stratify treatment groups in clinical trials and should guide inclusion criteria in clinical trials, which in turn increases the power to detect clinically relevant differences.

Age Factors↗

PubMed2005

Characterizing allelic associations from unphased diploid data by graphical modeling.

A method for estimating a graphical model to describe allelic associations between genetic loci is extended to use diploid genotypes rather than haploid data. It also provides haplotype frequency estimates, estimates of phase for sampled individuals, allows for missing or partial information, genotyping errors, and arbitrary penetrance functions. A data set of 688 unrelated individuals genotyped on 25 genetic loci is used to illustrate haplotype frequency estimation. The frequencies obtained are shown to be similar to those obtained by the PHASE program. We also illustrate how putative loci for traits can be included in the analysis in order to detect allele-phenotype associations. Haplotype reconstruction is illustrated on a standard set of 40 male X-chromosome haplotypes, randomly paired to simulate diploid genotype data. The novel method is shown to be comparable to most existing ones, though the PHASE method does consistently better on this problem. The graphical model approach is shown to have some advantages in terms of tractability and can be used to select informative subsets of loci and to map loci influencing phenotypes.

Alleles↗

PubMed2001

Using dose addition to estimate cumulative risks from exposures to multiple chemicals.

The Food Quality Protection Act (FQPA) of 1996 requires the EPA to consider the cumulative risk from exposure to multiple chemicals that have a common mechanism of toxicity. Three methods, hazard index (HI), point-of-departure index (PODI), and toxicity equivalence factor (TEF), have commonly been considered to estimate the cumulative risk. These methods are based on estimates of ED(10) (point of departure) and reference doses from the dose-response functions of individual chemicals. They do not incorporate the actual dose-response function of the mixture from multiple chemical exposures. Dose addition is considered to be an appropriate approach to cumulative risk assessment because it assumes that the chemicals of interest act in accordance with a common mode of action (a similar action). This paper proposes a formal statistical procedure to estimate the cumulative risk by fitting the dose-response model of the mixture under dose addition. The relative potency between two chemicals is estimated directly from the joint dose response model of the mixture. An example data set of four drugs representing four chemicals is used to illustrate the proposed procedure and compare it to the HI, PODI, and TEF methods.

Dose-Response Relationship, Drug↗

PubMed1989

QUAD: a computer package for the analysis of QUantal Assay Data.

The computer package QUAD has been developed at the University of Kent, U.K. It is menu driven and written in Advanced BASIC. It runs on IBM PC compatible machines equipped with a suitable graphics facility such as CGA or simulated CGA. QUAD is available on a floppy disk, for a small handling charge. QUAD has four main functions: it performs a logit analysis of quantal assay data; it provides a flexible way of analysing the data, allowing dose transformations and providing alternative confidence intervals for EDp values; it produces a range of diagnostics for assessing the fit of models to data; it provides and fits two families of extended models, each containing the logit as a special case. The package makes use of the latest statistical research, and fitted models are displayed by means of the good graphics facilities available on microcomputers. This document describes the facilities available in detail, and provides and discusses, illustrations of the package at work. QUAD has been designed as a pilot package. Further additions and developments are planned and described later.

Animals↗

PubMed1992

Effects of growth curve parameters on cow efficiency.

Weight-age data from 50 Retinta beef cows from 8 to 97 mo of age located in southwestern Spain were fitted to von Bertalanffy, Brody, and Richards functions to determine the relationship between growth curve parameters and cow efficiency. Only cows having at least 31 weights were included in the analysis. Von Bertalanffy, Brody, and Richards functions were fitted to weights of each cow. Relevant parameters of the three functions are A and K, associated with the asymptotic mature weight and rate of maturing, respectively. Criteria for comparisons among the three functions were computing difficulty, goodness of fit, and lack of bias of A. Productivity indicators were number of calves weaned during the first five calving seasons (NC), average birth weight (BWT), average weaning weight (WW), and average weaning weight per cow per year (WWY). The von Bertalanffy function was selected as the most appropriate. Least squares means for A and K were 650 +/- 8.17 kg and .038 +/- .001 mo-1, respectively. The values of NC, BWT, WW, and WWY were 4.0 +/- .11 calves, 38.2 +/- .4 kg, 218 +/- 5 kg, and 172 +/- 5 kg, respectively. Regression analysis for A indicated a decrease in NC when mature weight increased (P less than .05). There was a nonsignificant trend for heavier cows (higher A) to have calves with heavier BWT or WW. The value of WWY increased (P less than .05) with increased maturing rate (K) of cows. No significant associations were found between K and BWT or WW.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2004

Intraspecies sequence comparisons for annotating genomes.

Analysis of sequence variation among members of a single species offers a potential approach to identify functional DNA elements responsible for biological features unique to that species. Due to its high rate of allelic polymorphism and ease of genetic manipulability, we chose the sea squirt, Ciona intestinalis, to explore intraspecies sequence comparisons for genome annotation. A large number of C. intestinalis specimens were collected from four continents, and a set of genomic intervals were amplified, resequenced, and analyzed to determine the mutation rates at each nucleotide in the sequence. We found that regions with low mutation rates efficiently demarcated functionally constrained sequences: these include a set of noncoding elements, which we showed in C. intestinalis transgenic assays to act as tissue-specific enhancers, as well as the location of coding sequences. This illustrates that comparisons of multiple members of a species can be used for genome annotation, suggesting a path for the annotation of the sequenced genomes of organisms occupying uncharacterized phylogenetic branches of the animal kingdom. It also raises the possibility that the resequencing of a large number of Homo sapiens individuals might be used to annotate the human genome and identify sequences defining traits unique to our species.

Animals↗

PubMed2000

Mother's willingness to pay for her own and her child's health: a contingent valuation study in Taiwan.

We use the contingent valuation (CV) method to estimate mothers' willingness to pay (WTP) to protect themselves and their children from suffering a minor illness-a cold-in Taiwan. WTP is specified as a hedonic function of the duration and severity of the cold (measured alternatively by symptoms experienced and the Quality of Well-Being (QWB) index) and of respondents' socioeconomic characteristics. The average mother is willing to pay more to protect her child than herself from suffering a cold. Median WTP to avoid the average mother's and child's colds are US$37 and US$57, respectively. Adjusting for the greater duration and severity of the average mother's cold suggests that WTP to prevent comparable illnesses is approximately twice as large for the child as for the mother. We also find that mother's WTP is about 20% greater to prevent a son's than a daughter's illness.

Adult↗

PubMedDate not supplied

Region-specific age at onset of beta-amyloid in dogs.

Cortical patterns of beta-amyloid (Abeta) deposition were evaluated in 40 beagle dogs ranging in age from 2 to 18 years. Abeta deposition in the prefrontal, occipital, parietal and entorhinal cortices was visualized by using an antibody against Abeta1-42. A logistic regression was used to estimate differences in age-at-onset and rate of deposition of Abeta as a function of brain region. The earliest and most consistent site of Abeta deposition with age was in the prefrontal cortex. Entorhinal Abeta deposition was not consistently observed until the age of 14 years, but was present in a subset of dogs under the age of 14 years. These regional vulnerabilities to Abeta accumulation are similar to those seen in the aging human. By using parameters derived from regression analyses, it may be possible to predict the presence of Abeta within specific brain regions in individual dogs. We propose that these models will be a useful tool to evaluate interventions that delay the age of onset or slow the rate of accumulation of Abeta in the dog.

Aging↗

PubMed2005

Simultaneous inference of selection and population growth from patterns of variation in the human genome.

Natural selection and demographic forces can have similar effects on patterns of DNA polymorphism. Therefore, to infer selection from samples of DNA sequences, one must simultaneously account for demographic effects. Here we take a model-based approach to this problem by developing predictions for patterns of polymorphism in the presence of both population size change and natural selection. If data are available from different functional classes of variation, and a priori information suggests that mutations in one of those classes are selectively neutral, then the putatively neutral class can be used to infer demographic parameters, and inferences regarding selection on other classes can be performed given demographic parameter estimates. This procedure is more robust to assumptions regarding the true underlying demography than previous approaches to detecting and analyzing selection. We apply this method to a large polymorphism data set from 301 human genes and find (i) widespread negative selection acting on standing nonsynonymous variation, (ii) that the fitness effects of nonsynonymous mutations are well predicted by several measures of amino acid exchangeability, especially site-specific methods, and (iii) strong evidence for very recent population growth.

Computational Biology↗

PubMed2006

One billion years of bZIP transcription factor evolution: conservation and change in dimerization and DNA-binding site specificity.

The genomic era has revealed that the large repertoire of observed animal phenotypes is dependent on changes in the expression patterns of a finite number of genes, which are mediated by a plethora of transcription factors (TFs) with distinct specificities. The dimerization of TFs can also increase the complexity of a genetic regulatory network manifold, by combining a small number of monomers into dimers with distinct functions. Therefore, studying the evolution of these dimerizing TFs is vital for understanding how complexity increased during animal evolution. We focus on the second largest family of dimerizing TFs, the basic-region leucine zipper (bZIP), and infer when it expanded and how bZIP DNA-binding and dimerization functions evolved during the major phases of animal evolution. Specifically, we classify the metazoan bZIPs into 19 families and confirm the ancient nature of at least 13 of these families, predating the split of the cnidaria. We observe fixation of a core dimerization network in the last common ancestor of protostomes-deuterostomes. This was followed by an expansion of the number of proteins in the network, but no major dimerization changes in interaction partners, during the emergence of vertebrates. In conclusion, the bZIPs are an excellent model with which to understand how DNA binding and protein interactions of TFs evolved during animal evolution.

Animals↗

PubMed1992

Combined effects of body size, parity, and menstrual events on breast cancer incidence in seven countries.

A biologically motivated breast cancer incidence rate function was fit to data from a published case-control study conducted in countries whose incidence is high (Wales and the United States), moderate (Brazil, Greece, and Yugoslavia), and low (Japan and Taiwan). The data include personal characteristics of 3,925 breast cancer cases and 11,327 controls interviewed in selected hospitals in 1964-1968. Parameters in the function specify the dependence of age-specific breast cancer incidence rates on age at menarche, age at menopause, occurrence and timing of full-term pregnancies, and body mass. Parameters were estimated separately for high-, moderate-, and low-risk countries. Examination of residuals provided little evidence of inadequacy of the fitted function in describing combined effects of the characteristics studied. The following patterns were seen in all three risk groups: 1) Incidence rates jump to a higher level after first childbirth, but then increase with age more slowly thereafter. 2) Rates increase with age more slowly after menopause than before. 3) Rates change quadratically with body mass index among all women, although the main trend varies: Rates decrease with body mass among premenopausal women in high-risk countries, but increase with body mass in all other groups of women. Similarities of parameter estimates across countries suggest that reproductive events and body fat exert similar effects on all women, regardless of breast cancer rates in their country of residence.

Adult↗

PubMed1992

[Methods of risk assessment from data of experimental carcinogenesis studies].

A comparison of the carcinogenic potencies of different substances and an assessment of the risk to exposed people can contribute significantly to the management of carcinogenic hazards including adequate regulatory decisions. A mathematical estimation of the risk caused by a certain height of exposure is usually done under the assumption of a linear dose-response relationship by means of an arithmetical factor which gives the ratio of risk to dose in the low-response range and which has to be found on the basis of epidemiological or experimental data. This work deals with calculations of risk/dose ratios from the data of three carcinogenicity tests by means of statistical methods. The influence of the selection of mathematical model, background assumption and the point of the function chosen for the calculation of the ratio was tested. The results show that an additivity assumption for the background leads to linearity of the curve in the low-response range such that the ratios calculated with different models (multistage, weibull, logit, probit) or for different points of the functions do not differ significantly within the data sets tested. Even under the assumption of independence of the background risk the influence of the model selected is still small if the ratios are calculated for the lowest experimental dose or for an exposure associated risk of 1%. Risk/dose ratios calculated by one of these methods utilize the information of several experimental groups. They seem to be well suited for a direct comparison of the potency of different carcinogens and as a basis for an assessment of the carcinogenic risk to humans, which can serve as a measure of the hazard of a single exposed person or may give an idea about the tumour incidences to be expected within an exposed population.

Administration, Oral↗

PubMed2004

A pilot trial comparing cerebral perfusion pressure-targeted therapy to intracranial pressure-targeted therapy in children with severe traumatic brain injury.

OBJECT: The authors sought to compare cerebral perfusion pressure (CPP)- with intracranial pressure (ICP)-targeted therapy in children with severe traumatic brain injury (TBI). METHODS: A randomized controlled trial was developed to assess CPP and ICP therapies in 17 children (range 15 months-15 years of age) with poststabilization Glasgow Coma Scale (GCS) scores of less than or equal to 8 who were admitted to a pediatric intensive care unit at a Level I trauma center. Goals in the ICP group were to maintain ICP lower than 20 mm Hg and CPP higher than 50 mm Hg. In the CPP group, goals were to maintain CPP higher than 70 mm Hg for patients at least 2 years old and higher than 60 mm Hg for patients younger than 2 years of age. The study outcomes were death or functional outcome at 1 year postinjury. The median GCS scores in the CPP group (12 patients) and the ICP group (five patients) were 6 and 7, respectively. In the CPP group, two patients died, one was lost to follow up, four were unimpaired, and five had mild impairment. In the ICP group, all patients survived; one was lost to follow up, two had mild impairment, and two had hemiparesis and moderate impairment. There were four unimpaired survivors in the CPP arm compared with none in the ICP arm (p = 0.08). CONCLUSIONS: The CPP method appears to be safe, although this feasibility study does not establish that the CPP therapy is superior to ICP therapy.

Adolescent↗

PubMed2000

Statistical analysis of nonlinear parameter estimation for Monod biodegradation kinetics using bivariate data.

A nonlinear regression technique for estimating the Monod parameters describing biodegradation kinetics is presented and analyzed. Two model data sets were taken from a study of aerobic biodegradation of the polycyclic aromatic hydrocarbons (PAHs), naphthalene and 2-methylnaphthalene, as the growth-limiting substrates, where substrate and biomass concentrations were measured with time. For each PAH, the parameters estimated were: q(max), the maximum substrate utilization rate per unit biomass; K(S), the half-saturation coefficient; and Y, the stoichiometric yield coefficient. Estimating parameters when measurements have been made for two variables with different error structures requires a technique more rigorous than least squares regression. An optimization function is derived from the maximumlikelihood equation assuming an unknown, nondiagonal covariance matrix for the measured variables. Because the derivation is based on an assumption of normally distributed errors in the observations, the error structures of the regression variables were examined. Through residual analysis, the errors in the substrate concentration data were found to be distributed log-normally, demonstrating a need for log transformation of this variable. The covariance between ln C and X was found to be small but significantly nonzero at the 67% confidence level for NPH and at the 94% confidence level for 2MN. The nonlinear parameter estimation yielded unique values for q(max), K(S), and Y for naphthalene. Thus, despite the low concentrations of this sparingly soluble compound, the data contained sufficient information for parameter estimation. For 2-methylnaphthalene, the values of q(max) and K(S) could not be estimated uniquely; however, q(max)/K(S) was estimated. To assess the value of including the relatively imprecise biomass concentration data, the results from the bivariate method were compared with a univariate method using only the substrate concentration data. The results demonstrated that the bivariate data yielded a better confidence in the estimates and provided additional information about the model fit and model adequacy. The combination of the value of the bivariate data set and their nonzero covariance justifies the need for maximum likelihood estimation over the simpler nonlinear least squares regression.

Biodegradation, Environmental↗

PubMed2000

Efficient utilization of echocardiography for the assessment of left ventricular systolic function.

BACKGROUND: We hypothesized that patients could be selected for echocardiographic evaluation of left ventricular (LV) systolic function on the basis of historic, clinical, radiographic, and electrocardiographic criteria. METHODS AND RESULTS: We prospectively evaluated 300 consecutive inpatients referred for the echocardiographic assessment of LV function, of whom 124 (41%) had LV systolic dysfunction (LVSD) (LV ejection fraction <0.45). Among the historic variables, male sex was the only predictor of LVSD, whereas of the abnormal physical and radiographic findings, cardiomegaly on chest radiography was the only predictor. Among the electrocardiographic findings, the presence of left bundle branch block was positively correlated with the presence of LVSD, whereas a normal electrocardiogram was negatively correlated with this finding. Only 2 patients with LVSD had a normal electrocardiogram. The addition of significant predictors on physical examination and chest radiography doubled the predictive value of the historic variables for determining LVSD. The addition of electrocardiographic findings further doubled the predictive value of the model. Almost 45% of the predictive power of the final multivariate model (chi-square of 48 of the total chi-square of 108) was based on the absence of normal electrocardiogram in patients with LVSD. When chest radiographic findings were excluded from the model, the overall predictive power of the model did not change, with the normal electrocardiogram gaining greater prominence: Full 56% of the predictive power of the model (chi-square of 60 of the total chi-square of 108) resided in the ability of a normal electrocardiogram to discriminate between patients with and those without LVSD. CONCLUSIONS: Historic, chest radiographic, and electrocardiographic variables can be used to predict low likelihood of LVSD on echocardiography. In particular, when the electrocardiogram is normal, it is extremely unlikely to have LVSD. It can be argued that such patients should not be referred for echocardiography.

Aged↗