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Results for “Likelihood Functions”

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PubMed1999

A cognitive analysis of server intervention policies: perceptions of bar owners and servers.

OBJECTIVE: The present study examined the underlying psychological variables relevant to alcohol server intervention policies. The focus of the research was the theoretical examination of college bar owners' and servers' attitudes and beliefs about server intervention policies. METHOD: Owners (n = 185) and servers (n = 185) of college bars were asked about their attitudes and perceived cognitive outcomes regarding server intervention policies. RESULTS: Although the findings revealed no statistical differences between owners and servers on their attitudes toward the different server intervention policies, statistical differences were found between the different policies (p < .05). Favorable policies focused on providing services to customers, whereas unfavorable policies focused on limiting the sales of alcohol. Finally, structural equation modeling revealed perceived cognitive outcomes related to the attitudes toward different server intervention policies. CONCLUSIONS: According to the present study's theoretical orientation, the attitudes are likely to have a direct influence on the adoption of policies or, on the part of the server, compliance with the policies. These attitudes toward the policies were found to be a function of the perceived hassle of implementing the policies and how effective the policy was in preventing driving under the influence.

Accidents, Traffic↗

PubMed2004

Comparison of site-specific rate-inference methods for protein sequences: empirical Bayesian methods are superior.

The degree to which an amino acid site is free to vary is strongly dependent on its structural and functional importance. An amino acid that plays an essential role is unlikely to change over evolutionary time. Hence, the evolutionary rate at an amino acid site is indicative of how conserved this site is and, in turn, allows evaluation of its importance in maintaining the structure/function of the protein. When using probabilistic methods for site-specific rate inference, few alternatives are possible. In this study we use simulations to compare the maximum-likelihood and Bayesian paradigms. We study the dependence of inference accuracy on such parameters as number of sequences, branch lengths, the shape of the rate distribution, and sequence length. We also study the possibility of simultaneously estimating branch lengths and site-specific rates. Our results show that a Bayesian approach is superior to maximum-likelihood under a wide range of conditions, indicating that the prior that is incorporated into the Bayesian computation significantly improves performance. We show that when branch lengths are unknown, it is better first to estimate branch lengths and then to estimate site-specific rates. This procedure was found to be superior to estimating both the branch lengths and site-specific rates simultaneously. Finally, we illustrate the difference between maximum-likelihood and Bayesian methods when analyzing site-conservation for the apoptosis regulator protein Bcl-x(L).

Animals↗

PubMed1999

Indication of linkage of serum IgE levels to the interleukin-4 gene and exclusion of the contribution of the (-590 C to T) interleukin-4 promoter polymorphism to IgE variation.

Previous segregation analysis of a sample of 234 randomly selected Australian families showed evidence for a recessive major gene controlling serum immunoglobulin E (IgE) levels independently of the specific response to allergens (SRA). Since linkage has been recently reported between serum IgE levels and the 5q candidate region spanning the interleukin-4 (IL-4) gene, we investigated whether the recessive major gene detected by segregation analysis was linked to the IL-4 region and whether polymorphisms within the IL-4 gene were associated with IgE levels. Both sib-pair method and combined segregation and linkage analysis using the regressive models were applied to our data. Whereas there was no evidence of linkage of total IgE levels to the IL-4 region, an indication of linkage (P values ranging between 0.01 and 0.03) was found between IgE levels adjusted for SRA and two IL-4 polymorphisms: one dinucleotide repeat in intron 2 of the IL-4 gene and a single nucleotide (-590 C to T) polymorphism in the IL-4 promoter. However, the putative IL-4 linked gene did not appear to be in linkage disequilibrium with either of these two polymorphisms. A contribution of the IL-4 promoter polymorphism, presumed to be a potential functional variant influencing IgE variation, was also excluded.

Adolescent↗

PubMed2002

Clinical, radiological and functional follow-up after surgical decompression of double aortic arch.

BACKGROUND: Double aortic arch (DAA) is a congenital vascular anomaly that causes tracheal and oesophageal compression. It requires surgical intervention in patients with severe symptoms. OBJECTIVE: To evaluate the clinical, radiological and functional follow-up after surgical relief of the compression. MATERIALS AND METHODS: Ten children (seven boys) with DAA were operated on at a mean age of 1.3 years (range 0.2-7.5). At a mean age of 10.1 years (range 5-18 years), a follow-up study was performed that included clinical, radiological and functional parameters. RESULTS: Seven children reported only mild respiratory symptoms and some trouble with swallowing. Preoperative fluoroscopy with spot images showed the mean tracheal diameter at the level of stenosis to be 37+/-23% of the maximal diameter. At the time of follow-up, this was 70+/-13%. The mean of the oesophageal diameter was 39+/-20% preoperatively and 47+/-16% postoperatively. Maximal expiratory flow volume (MEFV) curves of seven children showed typical characteristics of intrathoracic upper airway obstruction. Mean peak expiratory flow was significantly reduced (77+/-10% of predicted, P<0.0001). Bronchial hyper-reactivity, tested by methacholine challenge, was found in two patients. CONCLUSIONS: There was marked relief of clinical symptoms after surgical decompression of DAA in all patients. In spite of this, radiological narrowing of trachea and oesophagus persisted and lung function results were abnormal at long-term follow-up.

Adolescent↗

PubMed2006

Relaxation of selective constraint on dog mitochondrial DNA following domestication.

The domestication of dogs caused a dramatic change in their way of life compared with that of their ancestor, the gray wolf. We hypothesize that this new life style changed the selective forces that acted upon the species, which in turn had an effect on the dog's genome. We sequenced the complete mitochondrial DNA genome in 14 dogs, six wolves, and three coyotes. Here we show that dogs have accumulated nonsynonymous changes in mitochondrial genes at a faster rate than wolves, leading to elevated levels of variation in their proteins. This suggests that a major consequence of domestication in dogs was a general relaxation of selective constraint on their mitochondrial genome. If this change also affected other parts of the dog genome, it could have facilitated the generation of novel functional genetic diversity. This diversity could thus have contributed raw material upon which artificial selection has shaped modern breeds and may therefore be an important source of the extreme phenotypic variation present in modern-day dogs.

Animals↗

PubMed2003

Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling.

Receptors for sex and adrenal steroid hormones are absent from fully sequenced invertebrate genomes and have not been recovered from other invertebrates. Here we report the isolation of an estrogen receptor ortholog from the mollusk Aplysia californica and the reconstruction, synthesis, and experimental characterization of functional domains of the ancestral protein from which all extant steroid receptors (SRs) evolved. Our findings indicate that SRs are extremely ancient and widespread, having diversified from a primordial gene before the origin of bilaterally symmetric animals, and that this ancient receptor had estrogen receptor-like functionality. This gene was lost in the lineage leading to arthropods and nematodes and became independent of hormone regulation in the Aplysia lineage.

Amino Acid Sequence↗

PubMed1979

The discriminative efficiency of the Bayley Scales of Infant Development.

This study was designed to determine the discriminative efficiency of the Bayley Mental and Motor Scales for classifying infants as neurologically suspicious and neurologically normal. The two groups employed in the study were formed on the basis of the results from comprehensive neurological examinations performed at ages 1 and 7. Three discriminant function analyses were conducted, one for each scale separately and a third incorporating both scales using a stepwise procedure. Efficiency was measured in terms of number of correct and incorrect classifications, false positive and false negative errors, and validity coefficients. Comparisons among the analyses were examined by means of relative discrimination power and incremental validity. The findings suggested that the Motor Scale provides the most accurate identification of infants with suspected neurological impairments. A statistically significant likelihood discriminant function derived from both scales yielded some additional discriminative power. The law of parsimony, however, dictated the use of the single Motor Scale.

Child↗

PubMed2006

Are fMRI event-related response constant in time? A model selection answer.

An accurate estimation of the hemodynamic response function (HRF) in functional magnetic resonance imaging (fMRI) is crucial for a precise spatial and temporal estimate of the underlying neuronal processes. Recent works have proposed non-parametric estimation of the HRF under the hypotheses of linearity and stationarity in time. Biological literature suggests, however, that response magnitude may vary with attention or ongoing activity. We therefore test a more flexible model that allows for the variation of the magnitude of the HRF with time in a maximum likelihood framework. Under this model, the magnitude of the HRF evoked by a single event may vary across occurrences of the same type of event. This model is tested against a simpler model with a fixed magnitude using information theory. We develop a standard EM algorithm to identify the event magnitudes and the HRF. We test this hypothesis on a series of 32 regions (4 ROIS on eight subjects) of interest and find that the more flexible model is better than the usual model in most cases. The important implications for the analysis of fMRI time series for event-related neuroimaging experiments are discussed.

Algorithms↗

PubMed2006

Polynomial spline estimation and inference of proportional hazards regression models with flexible relative risk form.

The Cox proportional hazards model usually assumes an exponential form for the dependence of the hazard function on covariate variables. However, in practice this assumption may be violated and other relative risk forms may be more appropriate. In this article, we consider the proportional hazards model with an unknown relative risk form. Issues in model interpretation are addressed. We propose a method to estimate the relative risk form and the regression parameters simultaneously by first approximating the logarithm of the relative risk form by a spline, and then employing the maximum partial likelihood estimation. An iterative alternating optimization procedure is developed for efficient implementation. Statistical inference of the regression coefficients and of the relative risk form based on parametric asymptotic theory is discussed. The proposed methods are illustrated using simulation and an application to the Veteran's Administration lung cancer data.

Algorithms↗

PubMed1997

An empirical comparison of two semi-parametric approaches for the estimation of covariate effects from multivariate failure time data.

We conducted a simulation study to compare two semi-parametric approaches for the estimation of covariate effects from multivariate failure time data. The first approach was developed by Wei, Lin and Weissfeld (WLW) and the second by Liang, Self and Chang (LSC). Based on the simulation results we recommend Wei, Lin and Weissfeld's method for the situations with identical covariates and high correlations between the failure times. When the covariates are independent, LSC produces smaller mean squared errors than WLW, although at the expense of larger bias. We also compared four computer programs for implementing Wei, Lin and Weissfeld's approach: a FORTRAN program, MULCOX2; a SAS macro; the coxph function in S-plus, and a specialized software package for complex survey data (SUDAAN). Our comparison indicates that for large data sets, the speeds of the SAS macro and coxph are comparable, while MULCOX2- and SUDAAN took longer to run. However, MULCOX2 and coxph function in S-plus have the advantage of allowing time-dependent covariates, and SUDAAN has the advantage of handling complex survey data.

Adult↗

PubMed2003

A unified statistical and information theoretic framework for multi-modal image registration.

We formulate and interpret several registration methods in the context of a unified statistical and information theoretic framework. A unified interpretation clarifies the implicit assumptions of each method yielding a better understanding of their relative strengths and weaknesses. Additionally, we discuss a generative statistical model from which we derive a novel analysis tool, the auto-information function, as a means of assessing and exploiting the common spatial dependencies inherent in multi-modal imagery. We analytically derive useful properties of the auto-information as well as verify them empirically on multi-modal imagery. Among the useful aspects of the auto-information function is that it can be computed from imaging modalities independently and it allows one to decompose the search space of registration problems.

Algorithms↗

PubMed2000

Sequencing by hybridization with the generic 6-mer oligonucleotide microarray: an advanced scheme for data processing.

DNA sequencing by hybridization was carried out with a microarray of all 4(6) = 4,096 hexadeoxyribonucleotides (the generic microchip). The oligonucleotides immobilized in 100 x 100 x 20-microm polyacrylamide gel pads of the generic microchip were hybridized with fluorescently labeled ssDNA, providing perfect and mismatched duplexes. Melting curves were measured in parallel for all microchip duplexes with a fluorescence microscope equipped with CCD camera. This allowed us to discriminate the perfect duplexes formed by the oligonucleotides, which are complementary to the target DNA. The DNA sequence was reconstructed by overlapping the complementary oligonucleotide probes. We developed a data processing scheme to heighten the discrimination of perfect duplexes from mismatched ones. The procedure was united with a reconstruction of the DNA sequence. The scheme includes the proper definition of a discriminant signal, preprocessing, and the variational principle for the sequence indicator function. The effectiveness of the procedure was confirmed by sequencing, proofreading, and nucleotide polymorphism (mutation) analysis of 13 DNA fragments from 31 to 70 nucleotides long.

Algorithms↗

PubMed2000

Evidence for variable selective pressures at MC1R.

It is widely assumed that genes that influence variation in skin and hair pigmentation are under selection. To date, the melanocortin 1 receptor (MC1R) is the only gene identified that explains substantial phenotypic variance in human pigmentation. Here we investigate MC1R polymorphism in several populations, for evidence of selection. We conclude that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin production (black pigmentation) appears to be evolutionarily deleterious. Although many of the MC1R amino acid variants observed in non-African populations do affect MC1R function and contribute to high levels of MC1R diversity in Europeans, we found no evidence, in either the magnitude or the patterns of diversity, for its enhancement by selection; rather, our analyses show that levels of MC1R polymorphism simply reflect neutral expectations under relaxation of strong functional constraint outside Africa.

Africa↗

PubMed2003

Does the ADF fit function decrease when the kurtosis increases?

In this study we demonstrate how the asymptotically distribution-free (ADF) fit function is affected by (excessive) kurtosis in the observed data. More specifically, we address how different levels of univariate kurtosis affect fit values (and therefore fit indices) for misspecified factor models. By using numerical calculation, we show (for 13 factor models) that the probability limit F(0) of F empty set for the ADF fit function decreases considerably as the kurtosis increases. We also give a formal proof that the value of F(0) decreases monotonically with the kurtosis for a whole class of structural equation models.

Analysis of Variance↗

PubMed2002

Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages.

The nonsynonymous (amino acid-altering) to synonymous (silent) substitution rate ratio (omega = d(N)/d(S)) provides a measure of natural selection at the protein level, with omega = 1, >1, and <1, indicating neutral evolution, purifying selection, and positive selection, respectively. Previous studies that used this measure to detect positive selection have often taken an approach of pairwise comparison, estimating substitution rates by averaging over all sites in the protein. As most amino acids in a functional protein are under structural and functional constraints and adaptive evolution probably affects only a few sites at a few time points, this approach of averaging rates over sites and over time has little power. Previously, we developed codon-based substitution models that allow the omega ratio to vary either among lineages or among sites. In this paper we extend previous models to allow the omega ratio to vary both among sites and among lineages and implement the new models in the likelihood framework. These models may be useful for identifying positive selection along prespecified lineages that affects only a few sites in the protein. We apply those branch-site models as well as previous branch- and site-specific models to three data sets: the lysozyme genes from primates, the tumor suppressor BRCA1 genes from primates, and the phytochrome (PHY) gene family in angiosperms. Positive selection is detected in the lysozyme and BRCA genes by both the new and the old models. However, only the new models detected positive selection acting on lineages after gene duplication in the PHY gene family. Additional tests on several data sets suggest that the new models may be useful in detecting positive selection after gene duplication in gene family evolution.

Animals↗

PubMed1996

Quality of life of patients with end stage renal disease: a structural equation model.

In this study, the perceived quality of life (QOL) of 215 patients with and stage renal disease (ESRD) was examined. A LISREL model describing the patients' perceptions of their QOL was tested and, after some revisions, was found to be consistent with the data (chi 2 = 33.76, df = 25, p = 0.113). QOL was measured by: the Self-Anchoring Striving Scale, the Index of Well-Being, and the Time Trade-Off Technique. The model includes the patients medical characteristics, their health status, functional status, support and outlook. Outlook, functional status and treatment modality had significant direct effects on QOL. Support influenced QOL through the mediating variable, outlook. This study suggests that a theoretical reexamination of the measurement structure of QOL is warranted.

Activities of Daily Living↗

PubMed2002

Bootstrapping the lexicon: a computational model of infant speech segmentation.

Prelinguistic infants must find a way to isolate meaningful chunks from the continuous streams of speech that they hear. BootLex, a new model which uses distributional cues to build a lexicon, demonstrates how much can be accomplished using this single source of information. This conceptually simple probabilistic algorithm achieves significant segmentation results on various kinds of language corpora - English, Japanese, and Spanish; child- and adult-directed speech, and written texts; and several variations in coding structure - and reveals which statistical characteristics of the input have an influence on segmentation performance. BootLex is then compared, quantitatively and qualitatively, with three other groups of computational models of the same infant segmentation process, paying particular attention to functional characteristics of the models and their similarity to human cognition. Commonalities and contrasts among the models are discussed, as well as their implications both for theories of the cognitive problem of segmentation itself, and for the general enterprise of computational cognitive modeling.

Algorithms↗

PubMed2004

Prediction of the confidence interval of quantitative trait Loci location.

In 1997, Darvasi and Soller presented empirical predictions of the confidence interval of quantitative trait loci (QTL) location for dense marker maps in experimental crosses. They showed from simulation results for backcross and F2 populations from inbred lines that the 95% confidence interval was a simple function of sample size and the effect of the QTL. In this study, we derive by theory simple equations that can be used to predict any confidence interval and show that for the 95% confidence interval, they are in good agreement with the empirical results given by Darvasi and Soller. A general form of the confidence interval is given that also applies to other population structures (e.g., collections of sib pairs). Furthermore, the expected shape of the likelihood-ratio-test around the true QTL location is derived, which is shown to be extremely leptokurtic. It is shown that this shape explains why confidence intervals from the Log of Odds (LOD) drop-off method and bootstrap results frequently differ for real data sets.

Animals↗