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At least 1,639 records · Page 91Linked to original sources
PubMed2005

New ratios for the detection and classification of CJD in multisequence MRI of the brain.

We present a method for the analysis of deep grey brain nuclei for accurate detection of human spongiform encephalopathy in multisequence MRI of the brain. We employ T1, T2 and FLAIR-T2 MR sequences for the detection of intensity deviations in the internal nuclei. The MR data are registered to a probabilistic atlas and normalised in intensity prior to the segmentation of hyperintensities using a foveal model. Anatomical data from a segmented atlas are employed to refine the registration and remove false positives. The results are robust over the patient data and in accordance to the clinical ground truth. Our method further allows the quantification of intensity distributions in basal ganglia. sCJD patient FLAIR images are classified with a more significant hypersignal in caudate nuclei (10/10) and putamen (6/10) than in thalami. Defining normalised MRI measures of the intensity relations between the internal grey nuclei of patients, we robustly differentiate sCJD and variant CJD (vCJD) patients, as an attempt towards the automatic detection and classification of human spongiform encephalopathies.

Algorithms↗
PubMed2001

Dendritic spatial flicker of local membrane potential due to channel noise and probabilistic firing of hippocampal neurons in culture.

Whole-cell recordings and imaging of dissociated hippocampal neurons stained with voltage sensitive dye provide a new microscopic picture of neuronal excitation. This is the first attempt to combine imaging of active channel clusters on the geometry of live neurons and a theoretical approach. During single somatic action potentials and the back-invasion into the neurites, local mean potentials are generated at sites of active channel clusters which are unevenly distributed in the neuronal membrane. Similar mean membrane potentials are observed in the neurites and at the soma. Identical action potentials produce different spatial patterns of mean membrane potentials from trial to trial. This spatial variability is explained by the stochastic behavior of the channels in the clusters. When hippocampal neurons are excited by synaptic inputs, their evoked responses are probabilistic and generate variable spatial patterns of mean membrane potential trial after trial. Our stochastic model reproduces this random behavior by assuming that the voltage fluctuations generated by channel noise are added to the synaptic potentials reaching the soma. We demonstrate that the probability of action potential initiation depends on the strength of the synaptic input, the diameter of the dendrites and the relative positions of the channel clusters, of the synapse and of the soma.

Action Potentials↗
PubMed2002

Cost effectiveness of influenza vaccination for healthy persons between ages 65 and 74 years.

Healthy persons between 65 and 74 years of age represent a large proportion of the population in this age group. Internationally, there is a substantial variation in whether these people are included among the recommendations for routine influenza vaccination. We therefore conducted this study, updating an earlier analysis, to assess the health and economic benefits of routine influenza vaccination of healthy persons between 65 and 74 years of age. The health benefits associated with vaccination were estimated using the administrative data bases of a large HMO in the Minneapolis, St. Paul, Minnesota area. Multivariate models were used to estimate reductions in hospitalization and death associated with vaccination. The economic analysis took the societal perspective and presented the results as net cost or saving per 10,000 persons vaccinated and per death prevented. Direct and indirect monetary costs were included in the models and were estimated from the published literature. Monte Carlo simulation was used to conduct probabilistic sensitivity analysis in order to derive probability intervals for each estimate of net costs or savings. Over the six consecutive study seasons, 1990-1991 to 1995-1996, vaccination of healthy elderly person was associated with a 36% reduction in hospitalization for pneumonia or influenza (95% CI, 2-39%), an 18% reduction in hospitalization for all respiratory conditions (95% CI, -6 to 37%) and a 40% reduction in death (95% CI, 14-38%). Vaccination was also associated with cost savings in all scenarios evaluated. The findings of this study again affirm the value of an age-based strategy for routine influenza vaccination of all elderly persons including healthy elderly persons between 65 and 74 years.

Aged↗
PubMed2004

Multiple-sequence functional annotation and the generalized hidden Markov phylogeny.

MOTIVATION: Phylogenetic shadowing is a comparative genomics principle that allows for the discovery of conserved regions in sequences from multiple closely related organisms. We develop a formal probabilistic framework for combining phylogenetic shadowing with feature-based functional annotation methods. The resulting model, a generalized hidden Markov phylogeny (GHMP), applies to a variety of situations where functional regions are to be inferred from evolutionary constraints. RESULTS: We show how GHMPs can be used to predict complete shared gene structures in multiple primate sequences. We also describe shadower, our implementation of such a prediction system. We find that shadower outperforms previously reported ab initio gene finders, including comparative human-mouse approaches, on a small sample of diverse exonic regions. Finally, we report on an empirical analysis of shadower's performance which reveals that as few as five well-chosen species may suffice to attain maximal sensitivity and specificity in exon demarcation. AVAILABILITY: A Web server is available at http://bonaire.lbl.gov/shadower

Algorithms↗
PubMed2005

Accelerating, hyperaccelerating, and decelerating networks.

Many growing networks possess accelerating statistics where the number of links added with each new node is an increasing function of network size so the total number of links increases faster than linearly with network size. In particular, biological networks can display a quadratic growth in regulator number with genome size even while remaining sparsely connected. These features are mutually incompatible in standard treatments of network theory which typically require that every new network node possesses at least one connection. To model sparsely connected networks, we generalize existing approaches and add each new node with a probabilistic number of links to generate either accelerating, hyperaccelerating, or even decelerating network statistics in different regimes. Under preferential attachment for example, slowly accelerating networks display stationary scale-free statistics relatively independent of network size while more rapidly accelerating networks display a transition from scale-free to exponential statistics with network growth. Such transitions explain, for instance, the evolutionary record of single-celled organisms which display strict size and complexity limits.

Journal Article↗
PubMed2006

The cost-effectiveness of antiretroviral treatment in Khayelitsha, South Africa--a primary data analysis.

BACKGROUND: Given the size of the HIV epidemic in South Africa and other developing countries, scaling up antiretroviral treatment (ART) represents one of the key public health challenges of the next decade. Appropriate priority setting and budgeting can be assisted by economic data on the costs and cost-effectiveness of ART. The objectives of this research were therefore to estimate HIV healthcare utilisation, the unit costs of HIV services and the cost per life year (LY) and quality adjusted life year (QALY) gained of HIV treatment interventions from a provider's perspective. METHODS: Data on service utilisation, outcomes and costs were collected in the Western Cape Province of South Africa. Utilisation of a full range of HIV healthcare services was estimated from 1,729 patients in the Khayelitsha cohort (1,146 No-ART patient-years, 2,229 ART patient-years) using a before and after study design. Full economic costs of HIV-related services were calculated and were complemented by appropriate secondary data. ART effects (deaths, therapy discontinuation and switching to second-line) were from the same 1,729 patients followed for a maximum of 4 years on ART. No-ART outcomes were estimated from a local natural history cohort. Health-related quality of life was assessed on a sub-sample of 95 patients. Markov modelling was used to calculate lifetime costs, LYs and QALYs and uncertainty was assessed through probabilistic sensitivity analysis on all utilisation and outcome variables. An alternative scenario was constructed to enhance generalizability. RESULTS: Discounted lifetime costs for No-ART and ART were US$2,743 and US$9,435 over 2 and 8 QALYs respectively. The incremental cost-effectiveness ratio through the use of ART versus No-ART was US$1,102 (95% CI 1,043-1,210) per QALY and US$984 (95% CI 913-1,078) per life year gained. In an alternative scenario where adjustments were made across cost, outcome and utilisation parameters, costs and outcomes were lower, but the ICER was similar. CONCLUSION: Decisions to scale-up ART across sub-Saharan Africa have been made in the absence of incremental lifetime cost and cost-effectiveness data which seriously limits attempts to secure funds at the global level for HIV treatment or to set priorities at the country level. This article presents baseline cost-effectiveness data from one of the longest running public healthcare antiretroviral treatment programmes in Africa that could assist in enhancing efficient resource allocation and equitable access to HIV treatment.

Journal Article↗
PubMedDate not supplied

[Probabilistic reinforcement and neurotic breakdown in unrestrained dogs].

The substitution of a constant reinforcement for a random one with a probability of 0.5 in experiments on two dogs with a simple motor stereotype was attended with nervous breakdowns with motor excitation, inadequate orienting reactions or passive-defensive behaviour. The change in the probability of reinforcement from 0.5 to 0.3 had a positive effect in experiments on one dog, while in the other it developed drowsiness. In two other dogs with a complicated stereotype, the change in the mode of reinforcement was attended with a peculiar preventive effect of probabilistic, but ordered reinforcement in experimental surroundings, including signals with a probabilistic random reinforcement as well. In this case the dogs displayed primarily signs of emotional stress only. Behaviour was somewhat disturbed in one animal only when testing signals with a probabilistic random reinforcement.

Animals↗
PubMed2007

Attitudes, order and quantity: deterministic and direct probabilistic tests of unidimensional unfolding.

This article is the final in the series on unidimensional unfolding. The investigations of Kyngdon (2006b) and Michell (1994) were extended to include direct probabilistic tests of the quantitative and ordinal components of unfolding theory with the multinomial Dirichlet model (Karabatsos 2005); and tests of the higher order axiomatic conjoint measurement (ACM, Krantz, Luce, Suppes and Tversky (KLST) 1971) condition of triple cancellation. Strong Dirichlet model support for both the ordinal and quantitative components of unfolding was only found in datasets that satisfied at least double cancellation. In contrast, the Item Response Theory (IRT) simple hyperbolic cosine model for pairwise preferences (SHCMpp, Andrich 1995) fitted all datasets. The paper concluded the SHCMpp is suited to the instrumental rather than scientific task (Michell 2000) of psychological measurement; with the caveat of the problematic chi square fit statistic. The paper also presents original work by the second author on coherent tests of triple cancellation.

Attitude↗
PubMed2003

Probabilistic constraint satisfaction at the lexical/phonetic interface: evidence for gradient effects of within-category VOT on lexical access.

Research in speech perception has been dominated by a search for invariant properties of the signal that correlate with lexical and sublexical categories. We argue that this search for invariance has led researchers to ignore the perceptual consequences of systematic variation within such categories and that sensitivity to this variation may provide an important source of information for integrating information over time in speech perception. Data from a study manipulating VOT continua in words using an eye-movement paradigm indicate that lexical access shows graded sensitivity to within-category variation in VOT and that this sensitivity has a duration sufficient to be useful for information integration. These data support a model in which the perceptual system integrates information from multiple sources and from the surrounding temporal context using probabilistic cue-weighting mechanisms.

Eye Movements↗
PubMed2004

Curve-fitting overlapped bands: quantification and improvement of curve-fitting robustness in the presence of errors in the model and in the data.

Estimation of the band parameters of overlapped bands often relies on curve-fitting. It has been demonstrated that curve-fitting provides the maximum likelihood estimation of band parameters under a series of assumptions. One of these assumptions is that the curve-fitting model is correct and any error in the data is random. Under real conditions, we have to acknowledge the unavoidable presence of errors in the model and systematic errors in the data. Here, we derive an expression for the estimation of how these errors affect the quality of the parameters obtained from curve-fitting. In addition, we derive theoretical expressions to quantify the extent to which different methods can improve the curve-fitting robustness to these errors. The methods considered are: (i) deterministic and (ii) probabilistic constraints in the band parameters, (iii) curve-fitting band-narrowed data, and (iv) building a more accurate model. The theoretical expressions obtained are tested in the curve-fitting of a synthetic noisy spectrum with either baseline or band shape errors, and in the curve-fitting of the experimental infrared amide I band of the membrane protein bacteriorhodopsin.

Animals↗
PubMedDate not supplied

Probabilistic analysis of decision trees using symbolic algebra.

Uncertainty in medical decision making techniques occurs in the specification of both decision tree probabilities and utilities. Using a computer-based algebraic approach, methods for modeling this uncertainty have been formulated. This analytic procedure allows an exact calculation of the statistical variance at the final decision node using automated symbolic manipulation. Confidence and conditional confidence levels for the preferred decision are derived from gaussian theory, and the mutual information index that identifies probabilistically important tree variables is provided. The computer-based algebraic method is illustrated for a problem previously analyzed by Monte Carlo simulation. This methodology provides the decision analyst with a procedure to evaluate the outcome of specification uncertainty, in many decision problems, without resorting to Monte Carlo analysis.

Adult↗
PubMed2002

A computational account of altered error processing in older age: dopamine and the error-related negativity.

When participants commit errors or receive feedback signaling that they have made an error, a negative brain potential is elicited. According to Holroyd and Coles's (in press) neurocomputational model of error processing, this error-related negativity (ERN) is elicited when the brain first detects that the consequences of an action are worse than expected. To study age-related changes in error processing, we obtained performance and ERN measures of younger and high-functioning older adults. Experiment 1 demonstrated reduced ERN amplitudes in older adults in the context of otherwise intact brain potentials. This result could not be attributed to uncertainty about the required response in older adults. Experiment 2 revealed impaired performance and reduced response- and feedback-related ERNs of older adults in a probabilistic learning task. These age changes could be simulated by manipulation of a single parameter of the neurocomputational model, this manipulation corresponding to weakened phasic activity of the mesencephalic dopamine system.

Adolescent↗
PubMed2006

SPA: a probabilistic algorithm for spliced alignment.

Recent large-scale cDNA sequencing efforts show that elaborate patterns of splice variation are responsible for much of the proteome diversity in higher eukaryotes. To obtain an accurate account of the repertoire of splice variants, and to gain insight into the mechanisms of alternative splicing, it is essential that cDNAs are very accurately mapped to their respective genomes. Currently available algorithms for cDNA-to-genome alignment do not reach the necessary level of accuracy because they use ad hoc scoring models that cannot correctly trade off the likelihoods of various sequencing errors against the probabilities of different gene structures. Here we develop a Bayesian probabilistic approach to cDNA-to-genome alignment. Gene structures are assigned prior probabilities based on the lengths of their introns and exons, and based on the sequences at their splice boundaries. A likelihood model for sequencing errors takes into account the rates at which misincorporation, as well as insertions and deletions of different lengths, occurs during sequencing. The parameters of both the prior and likelihood model can be automatically estimated from a set of cDNAs, thus enabling our method to adapt itself to different organisms and experimental procedures. We implemented our method in a fast cDNA-to-genome alignment program, SPA, and applied it to the FANTOM3 dataset of over 100,000 full-length mouse cDNAs and a dataset of over 20,000 full-length human cDNAs. Comparison with the results of four other mapping programs shows that SPA produces alignments of significantly higher quality. In particular, the quality of the SPA alignments near splice boundaries and SPA's mapping of the 5' and 3' ends of the cDNAs are highly improved, allowing for more accurate identification of transcript starts and ends, and accurate identification of subtle splice variations. Finally, our splice boundary analysis on the human dataset suggests the existence of a novel non-canonical splice site that we also find in the mouse dataset. The SPA software package is available at http://www.biozentrum.unibas.ch/personal/nimwegen/cgi-bin/spa.cgi.

Algorithms↗
PubMed2003

Statistical shape analysis using non-Euclidean metrics.

The contribution of this paper is the adaptation of data driven methods for non-Euclidean metric decomposition of tangent space shape coordinates. The basic idea is to extend principal component analysis (PCA) to take into account the noise variance at different landmarks and at different shapes. We show examples where these non-Euclidean metric methods allow for easier interpretation by decomposition into meaningful modes of variation. The extensions to PCA are based on adaptation of maximum autocorrelation factors and the minimum noise fraction transform to shape decomposition. A common basis of the methods applied is the assessment of the annotation noise variance at individual landmarks. These assessments are based on local models or repeated annotations by independent operators. We show that the Molgedey-Schuster independent component analysis is equivalent to the maximum autocorrelation factors. Finally, the different subspace methods are compared using a probabilistic formulation based on their ability to represent the data.

Algorithms↗
PubMed1990

Probabilistic secretion of quanta from nerve terminals at synaptic sites on muscle cells: non-uniformity, autoinhibition and the binomial hypothesis.

A model of the secretion of a quantum at a release site is proposed in which, following the influx of calcium ions, synaptic vesicles are made available for release by the activation of kappa phosphorylation steps with rate alpha. At any time during this process the vesicles may become unavailable for secretion at rate gamma. On completion of the kappa phosphorylation steps the vesicles participate in the formation of a fusion pore with the terminal membrane to give exocytosis at rate delta. Changes in alpha, delta and kappa are shown to produce characteristic changes in the number and timecourse of quantal secretions following a nerve impulse, which are similar to those observed following drug treatments that are thought to act selectively on each of these processes. The number of quanta secreted from nerve terminals that consist of many release sites does not fluctuate much during a low frequency train of impulses: the variance is small compared with the mean level, so secretion follows binomial rather than Poisson statistics. A theory is derived that shows that variations in the probability of secretion amongst these release sites of any particular kind fails to reduce the variance of the total secretion from the terminal; Poisson rather than binomial statistics then still apply. The theory shows that an interaction between release sites is required to reduce this variance and such an effect is provided if secretion at a site inhibits secretion at nearby sites. Simulations show that incorporating this process of autoinhibition into the model reproduces the experimental observations on the effects of calcium ions on the binomial parameters p and n as well as on the relative constancy of p during facilitation and depression of quantal secretion. Methods for estimating the timecourse of changes in the probability of secretion at release sites following an impulse, by using either the time of occurrence of first, second, third or later quantal latencies, are given. These procedures show that current methods for estimating the time-dependent probability changes are inadequate for detecting interaction between release sites, such as autoinhibition, unless this is relatively large. Therefore, estimates from third quantal latencies are used.

Animals↗
PubMed1980

[Systems analysis and logico-mathematical modeling of syndromal predilection in delusional disorders].

The syndrome-forming effect of some factors in delusional psychoses was studied by the probabilistic statistical method. For each syndrome a combination of predilective correlations was found. A complex characteristic of the syndromal predilection of the disease permitted to evaluate more comprehensively not only its typical expression, but also possible deviations in specific cases. The formal assessment of pathogenetic correlations may be used for compiling computer programmes of psychoses analyses.

Acute Disease↗
PubMed1991

Analyses of multinomial mixture distributions: new tests for stochastic models of cognition and action.

Mixture distributions are formed from a weighted linear combination of 2 or more underlying basis distributions [g(x) = sigma j alpha j fj(x); sigma alpha j = 1]. They arise frequently in stochastic models of perception, cognition, and action in which a finite number of discrete internal states are entered probabilistically over a series of trials. This article reviews various distributional properties that have been examined to test for the presence of mixture distributions. A new multinomial maximum likelihood mixture (MMLM) analysis is discussed for estimating the mixing probabilities alpha j and the basis distributions fj(x) of a hypothesized mixture distribution. The analysis also generates a maximum likelihood goodness-of-fit statistic for testing various mixture hypotheses. Stochastic computer simulations characterize the statistical power of such tests under representative conditions. Two empirical studies of mental processes hypothesized to involve mixture distributions are summarized to illustrate applications of the MMLM analysis.

Arousal↗
PubMed2004

3D structure model of the principal neutralizing epitope of Minnesota HIV-1 isolate.

A hierarchical procedure, using a "bottom-up" strategy and combining (i). a probabilistic approach for estimating all possible starting structures, (ii). restrained molecular mechanics algorithms for preliminary selection of all energetically preferred conformers, as well as (iii). quantum chemical computations for refining their geometry, was used to study the structural properties of the HIV-MN neutralizing epitope in terms of NMR spectroscopy data. As a result, only one of initial structures matching the experimental and theoretical data was found to be well-ground for implementing the function of immunoreactive conformation of the virus immunogenic crown. The geometric parameters of this structure in water solution were shown to correspond to a double beta-turn conformation similar to that revealed in crystal for synthetic molecules imitating the central region of the HIV-MN V3 loop. The following conclusion was drawn from the comparative analysis of simulated structure with the one computed previously: the HIV-MN immunogenic tip has some inherent conformational flexibility that manifests at the alterations of hexapeptide environment and leads to the structural transitions changing the local conformation of the stretch of interest but retaining its spatial main chain fold. As a matter of record, the high resolution 3D structure model for the HIV-MN principal neutralization site was constructed, and its geometric parameters were compared with the corresponding characteristics of conformers derived earlier for describing the conformational features of immunogenic tip of gp120 from Thailand HIV-1 isolate.

Epitopes↗