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PubMed2005

Visual disability variables. II: The difficulty of tasks for a sample of low-vision patients.

OBJECTIVES: To test the validity and reliability of measures of visual ability and to evaluate the relation between measurements made at the task level and measurements made at the goal level of a hierarchical model for visual disability. DESIGN: Validation of a telephone-administered functional assessment instrument using Rasch analysis on self-assessment ratings. SETTING: Telephone interviews of respondents in their homes. PARTICIPANTS: Consecutive series of 600 outpatients with low vision. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Ordinal ratings of the difficulty in performing a subset of 337 tasks. Measures of the visual ability of each patient and the required visual ability to perform each task were made using the Andrich rating scale model. Measurement validity and reliability were tested statistically by comparing response patterns and distributions to measurement model expectations. RESULTS: Results were consistent with a single visual ability construct. Patients' visual ability estimated from task difficulty ratings agreed with estimates from goal difficulty ratings ( r =.74); the difficulty of individual goals was equal to the weighted average of the difficulties of subsidiary tasks ( r =.79). However, conclusions from the Rasch analysis were not confirmed by principal components analysis of item residuals, which indicated that visual ability had a 2-dimensional structure, with 1 factor related to mobility and the other related to reading. Factor analysis on person measures estimated from subsets of functionally grouped items confirmed the 2-dimensional structure of visual ability. CONCLUSIONS: Our study results confirm the hierarchical structure of the Activity Breakdown Structure model and show how the individualized Activity Inventory can produce measures of limitations in functional vision.

Activities of Daily Living↗

PubMed1998

Computational learning reveals coiled coil-like motifs in histidine kinase linker domains.

The recent rapid growth of protein sequence databases is outpacing the capacity of researchers to biochemically and structurally characterize new proteins. Accordingly, new methods for recognition of motifs and homologies in protein primary sequences may be useful in determining how these proteins might function. We have applied such a method, an iterative learning algorithm, to analyze possible coiled coil domains in histidine kinase receptors. The potential coiled coils have not yet been structurally characterized in any histidine kinase, and they appear outside previously noted kinase homology regions. The learning algorithm uses a combination of established sequence patterns in known coiled coil proteins and histidine kinase sequence data to learn to recognize efficiently this coiled coil-like motif in the histidine kinases. The common appearance of the structural motif in a functionally important part of the receptors suggests hypotheses for kinase regulation and signal transduction.

Algorithms↗

PubMed2006

Functional erythropoietin deficiency in patients with Type 2 diabetes and anaemia.

AIMS: Anaemia is a common finding in patients with diabetic nephropathy. Impaired production of erythropoietin is thought to be the predominant cause, as a result of renal microvascular disease. This study aims to determine the prevalence of functional erythropoietin deficiency in a cross-sectional survey of patients with Type 2 diabetes. METHODS: Clinical data on 604 patients with Type 2 diabetes were obtained, including a full blood count, iron indices and detailed history of diabetic complications. Erythropoietin levels were correlated with the presence of anaemia, iron deficiency and renal dysfunction. Functional erythropoietin deficiency was defined by erythropoietin levels in the normal range despite the presence of anaemia. RESULTS: Nineteen per cent of patients (n = 112) were anaemic, among whom erythropoietin deficiency (76%) and reduced iron availability (58%) were common findings. Over 90% of patients had erythropoietin deficiency, once those with reduced iron stores or availability were excluded. Most of these patients had moderate renal impairment (60%, n = 67). However, even in the absence of renal impairment, 71% of anaemic patients (n = 32/45) had functional erythropoietin deficiency, although most had other evidence of nephropathy. In addition, two-thirds of patients with reduced iron availability were unable to increase erythropoietin above the normal range. CONCLUSIONS: These findings confirm the failure of the kidney to produce erythropoietin in response to a falling haemoglobin is a key component to anaemia in diabetes. The likelihood of functional erythropoietin deficiency as a cause of anaemia is not dependent on the severity of renal impairment or excluded in diabetic patients with reduced iron stores or availability.

Adult↗

PubMed1995

Cognitive function and assessment of lung function in the elderly.

The feasibility of spirometry or respiratory impedance measurements for assessing lung function in the elderly was compared in 208 institutionalized patients with various degrees of cognitive function impairment. Respiratory impedance was determined by the forced oscillation technique. Cognitive function was assessed by the score for the mini-mental state (MMS) examination. Of the 208 patients, 126 had severe cognitive impairment (MMS < or = 17), 36 had mild impairment (18 < or = MMS < or = 23), and 46 had no impairment (MMS > or = 24). Of the 208 patients, respiratory impedance measurements were possible in 159, whereas in only 85 was spirometry possible. The overall difference between the feasibility rates for the spirometric and respiratory impedance measurements was highly significant (chi 2 = 71.4; p < 10(-6)). The difference between the feasibility rates for the two techniques was higher in the group of subjects with severe cognitive impairment than in the groups with mild impairment and no impairment, respectively. Among the 84 patients able to complete both tests, significant correlations were found between the spirometric and respiratory impedance measurements. These results indicate that respiratory impedance measurement seems a more useful tool than spirometry for assessing lung function in elderly patients whenever cognitive function is impaired.

Aged↗

PubMed2005

The relationship of functional status, nutritional assessment, and severity of illness to in-hospital mortality.

BACKGROUND: Prediction of in-hospital mortality may direct hospital resources towards those patients most at risk. A number of single domain risk instruments have been developed, indicating that functional status, nutritional assessment, and severity of illness individually predict in-hospital mortality. The interaction among these predictors is less well described. OBJECTIVE: To determine the relationship of functional status, nutritional assessment, and severity of illness to in-hospital mortality. DESIGN, SETTING, SUBJECTS: Cohort study of 1712 consecutive admissions over a one year period to an Internal Medical Service at a tertiary university teaching hospital. MAIN OUTCOME MEASURES: Death during hospital admission. RESULTS: Dependency in activities of daily living (OR = 3.37, 95% CI 1.78 to 6.37, p = 0.0002) and body mass index less than 20 (OR = 2.38, 95% CI 1.20 to 4.74, p = 0.01) predicted in-hospital mortality after adjusting for nutritional risk assessment, and severity of illness score. CONCLUSIONS: Impairment in functional status and low body mass index produce the best predictors of inhospital mortality, after adjusting for nutritional risk and severity of illness score. Among these factors, functional impairment may be amenable to correction.

Activities of Daily Living↗

PubMed2006

Eliciting utilities using functional methodology: people's disutilities for the adverse outcomes of cardiopulmonary resuscitation.

OBJECTIVE: To evaluate the functional methodology of Norman H. Anderson in eliciting utilities for health outcomes. METHODS: Lay people in Tours, France, rated the undesirability of 40 scenarios of possible outcomes of cardiopulmonary resuscitation on individual linear scales (Study 1) or on a single long scale (Study 2). The outcomes were either 1 of 8 undesirable outcomes, combined with 1 of 5 likelihoods, or else complete recovery, combined with the complementary likelihood. RESULTS: The mean utilities were consistent with previous studies. On the individual level, the internal coherence of most participants' ratings - defined as the consistency and regularity of the graphic representation of their ratings - improved in Study 1 from their 1st to their 2nd rating. The single scale took less time, but allowed participants to disregard the information about likelihood. CONCLUSIONS: Functional methodology provides a powerful means of checking on the understanding and consistency of each person whose utilities are elicited.

Adult↗

PubMed1998

Iterative and analytical reconstruction algorithms for varying-focal-length cone-beam projections.

In single photon emission computed tomography (SPECT), a varying-focal-length cone-beam collimator can be used to reduce the truncation problem and to maintain sensitivity when imaging the organ of interest. The collimator is constructed so that the collimator holes focus to a circular symmetric, spatially varying, focal point function. The focal length increases radially from the shortest focal length at the centre to the longest focal length at the periphery of the collimator. This paper describes a 3D backprojection-filtering (BF) algorithm for this varying-focal-length cone-beam geometry. The proposed algorithm is compared to an iterative ML-EM (maximum likelihood-expectation maximization) algorithm. The 3D Hoffman brain phantom and Defrise phantom are used in computer simulations. Since the maximum tilt angle of the projection rays is small for most realistic imaging geometries, the proposed algorithm provides a good approximation. When a circular orbit is used, the BF algorithm gives an exact reconstruction of the central slice.

Algorithms↗

PubMed2025

Penalized likelihood optimization for censored missing value imputation in proteomics.

Label-free bottom-up proteomics using mass spectrometry and liquid chromatography has long been established as one of the most popular high-throughput analysis workflows for proteome characterization. However, it produces data hindered by complex and heterogeneous missing values, which imputation has long remained problematic. To cope with this, we introduce Pirat, an algorithm that harnesses this challenge using an original likelihood maximization strategy. Notably, it models the instrument limit by learning a global censoring mechanism from the data available. Moreover, it estimates the covariance matrix between enzymatic cleavage products (ie peptides or precursor ions), while offering a natural way to integrate complementary transcriptomic information when multi-omic assays are available. Our benchmarking on several datasets covering a variety of experimental designs (number of samples, acquisition mode, missingness patterns, etc.) and using a variety of metrics (differential analysis ground truth or imputation errors) shows that Pirat outperforms all pre-existing imputation methods. Beyond the interest of Pirat as an imputation tool, these results pinpoint the need for a paradigm change in proteomics imputation, as most pre-existing strategies could be boosted by incorporating similar models to account for the instrument censorship or for the correlation structures, either grounded to the analytical pipeline or arising from a multi-omic approach.

Proteomics↗

PubMed1993

Robustness of some estimators for the analysis of covariance structures.

A sampling experiment was designed to evaluate the robustness of some estimators used in the analysis of covariance structures to misspecification of the discrepancy function in finite samples. The estimators were studied under four distribution (a multivariate normal, an elliptical, a non-elliptically symmetric, and an asymmetric multivariate distribution, and eight sample size (75, 150, 300, 600, 1200, 2400, 4800, 9600) conditions. Parameters of the composite direct product model for a 6-variable MTMM matrix were estimated using the Maximum Wishart Likelihood (MWL), generalized least squares (GLS), asymptotically distribution free (ADF), and approximate ADF (DADF) estimators. Browne's elliptical correction (CMWL) to the test statistic and standard errors for scale-invariant models was also made for each sample. Each of the 32 distribution-sample size conditions was replicated 300 times. The accuracy of the parameter estimates and estimated standard errors and the distribution of the test statistic were studied. The theoretically predicted importance of information contained in higher-order moments of arbitrary distributions was confirmed. Robustness of the MWL and normal theory GLS estimators cannot be taken for granted. Elliptical corrections may be a practical solution to some data analytic problems.

Female↗

PubMed2005

What are the effects of group cognitive behaviour therapy for voices? A randomised control trial.

BACKGROUND: Little evidence exists for the effects of psychological treatment on voices even though it is clear that CBT does affect delusions and symptoms overall. This study tested whether a group based on cognitive behavioural principles could produce beneficial effects on hallucinations. AIM: To test the effectiveness of group CBT on social functioning and severity of hallucinations. METHOD: Participants were included if they had a diagnosis of schizophrenia and experienced distressing auditory hallucinations (rated on the PANSS). They were randomly allocated to group CBT (N = 45) or a control group who received treatment as usual (N = 40). The two main outcomes were social functioning as measured by the Social Behaviour Schedule and the severity of hallucinations as measured by the total score on the Hallucinations Scale of PSYRATS. Assessments were carried out at baseline, 10 weeks (post therapy) and 36 weeks (six months following therapy). RESULTS: Mixed random effects models revealed significant improvement in social functioning (effect size 0.63 six months after the end of therapy). There was no general effect of group CBT on the severity of hallucinations. However, there was a large cluster effect of therapy group on the severity of hallucinations such that they were reduced in some but not all of the therapy groups. Improvement in hallucinations was associated with receiving therapy early in the trial and having very experienced therapists (extensive CBT training which included expert supervision for a series of individual cases for at least a year following initial training). CONCLUSION: Group CBT does improve social functioning but unless therapy is provided by experienced CBT therapists hallucinations are not reduced.

Adaptation, Psychological↗

PubMed2002

Linkage mapping of sex-specific differences.

Most current linkage analyses assume identical fractions of meiotic recombination between homologous marker loci of the two sexes. This assumption is not realistic, because considerable sex-related differences have been observed in recombination fraction. In this paper, a general EM-based algorithm is presented to estimate sex-specific recombination fractions for a mixed set of molecular markers segregating differently in a full-sib family derived from two heterozygous parents. The asymptotic variances of the estimates of linkage specifically for each of the parents are evaluated using a numerical analysis based on information functions. This approach will have important implications for precise gene mapping based on sex-specific linkage maps.

Algorithms↗

PubMed2005

New insights into the nature and phylogeny of prasinophyte antenna proteins: Ostreococcus tauri, a case study.

The basal position of the Mamiellales (Prasinophyceae) within the green lineage makes these unicellular organisms key to elucidating early stages in the evolution of chlorophyll a/b-binding light-harvesting complexes (LHCs). Here, we unveil the complete and unexpected diversity of Lhc proteins in Ostreococcus tauri, a member of the Mamiellales order, based on results from complete genome sequencing. Like Mantoniella squamata, O. tauri possesses a number of genes encoding an unusual prasinophyte-specific Lhc protein type herein designated "Lhcp". Biochemical characterization of the complexes revealed that these polypeptides, which bind chlorophylls a, b, and a chlorophyll c-like pigment (Mg-2,4-divinyl-phaeoporphyrin a5 monomethyl ester) as well as a number of unusual carotenoids, are likely predominant. They are retrieved to some extent in both reaction center I (RCI)- and RCII-enriched fractions, suggesting a possible association to both photosystems. However, in sharp contrast to previous reports on LHCs of M. squamata, O. tauri also possesses other LHC subpopulations, including LHCI proteins (encoded by five distinct Lhca genes) and the minor LHCII polypeptides, CP26 and CP29. Using an antibody against plant Lhca2, we unambiguously show that LHCI proteins are present not only in O. tauri, in which they are likely associated to RCI, but also in other Mamiellales, including M. squamata. With the exception of Lhcp genes, all the identified Lhc genes are present in single copy only. Overall, the discovery of LHCI proteins in these prasinophytes, combined with the lack of the major LHCII polypeptides found in higher plants or other green algae, supports the hypothesis that the latter proteins appeared subsequent to LHCI proteins. The major LHC of prasinophytes might have arisen prior to the LHCII of other chlorophyll a/b-containing organisms, possibly by divergence of a LHCI gene precursor. However, the discovery in O. tauri of CP26-like proteins, phylogenetically placed at the base of the major LHCII protein clades, yields new insight to the origin of these antenna proteins, which have evolved separately in higher plants and green algae. Its diverse but numerically limited suite of Lhc genes renders O. tauri an exceptional model system for future research on the evolution and function of LHC components.

Amino Acid Sequence↗

PubMed1992

Multidimensional ordering of psychopathology. A factor-analytic study using the Comprehensive Psychopathological Rating Scale.

The aim of the study was to search for a multidimensional order in the psychopathology of the functional mental disorders in general. A heterogeneous group of 192 patients was investigated by means of a semistructured interview based on the Comprehensive Psychopathological Rating Scale. Principal component factor analysis revealed 5 clinically meaningful dimensions interpretable as representing dysregulation of emotion and motivation, perceptual and behavioural disintegration and dysregulation of autonomic functions.

Adolescent↗

PubMedDate not supplied

The evolution of acetyl-CoA synthase.

Acetyl-coenzyme A synthases (ACS) are Ni-Fe-S containing enzymes found in archaea and bacteria. They are divisible into 4 classes. Class I ACS's catalyze the synthesis of acetyl-CoA from CO2 + 2e-, CoA, and a methyl group, and contain 5 types of subunits (alpha, beta, gamma, delta, and epsilon). Class II enzymes catalyze essentially the reverse reaction and have similar subunit composition. Class III ACS's catalyze the same reaction as Class I enzymes, but use pyruvate as a source of CO2 and 2e-, and are composed of 2 autonomous proteins, an alpha 2 beta 2 tetramer and a gamma delta heterodimer. Class IV enzymes catabolize CO to CO2 and are alpha-subunit monomers. Phylogenetic analyses were performed on all five subunits. ACS alpha sequences divided into 2 major groups, including Class I/II sequences and Class III/IV-like sequences. Conserved residues that may function as ligands to the B- and C-clusters were identified. Other residues exclusively conserved in Class I/II sequences may be ligands to additional metal centers in Class I and II enzymes. ACS beta sequences also separated into two groups, but they were less divergent than the alpha's, and the separation was not as distinct. Class III-like beta sequences contained approximately 300 residues at their N-termini absent in Class I/II sequences. Conserved residues identified in beta sequences may function as ligands to active site residues used for acetyl-CoA synthesis. ACS gamma-sequences separated into 3 groups (Classes I, II, and III), while delta-sequences separated into 2 groups (Class I/II and III). These groups are less divergent than those of alpha sequences. ACS epsilon-sequence topology showed greater divergence and less consistency vis-à-vis the other subunits, possibly reflecting reduced evolutionary constraints due to the absence of metal centers. The alpha subunit phylogeny may best reflect the functional diversity of ACS enzymes. Scenarios of how ACS and ACS-containing organisms may have evolved are discussed.

Acetate-CoA Ligase↗

PubMed2006

Semiparametric regression in capture-recapture modeling.

Capture-recapture models were developed to estimate survival using data arising from marking and monitoring wild animals over time. Variation in survival may be explained by incorporating relevant covariates. We propose nonparametric and semiparametric regression methods for estimating survival in capture-recapture models. A fully Bayesian approach using Markov chain Monte Carlo simulations was employed to estimate the model parameters. The work is illustrated by a study of Snow petrels, in which survival probabilities are expressed as nonlinear functions of a climate covariate, using data from a 40-year study on marked individuals, nesting at Petrels Island, Terre Adélie.

Animals↗

PubMed2005

A human congenital myasthenia-causing mutation (epsilon L78P) of the muscle nicotinic acetylcholine receptor with unusual single channel properties.

A mutation in the epsilon subunit of the human nicotinic acetylcholine receptor (epsilonL78P) is known to cause a congenital slow channel myasthenic syndrome. We have investigated the changes in receptor function that result in the mutant receptor producing prolonged endplate currents, and consequent muscle damage. The rate constants for channel gating and for the binding and dissociation of acetylcholine were investigated by analysis of single ion channel recordings. A conventional mechanism with two non-equivalent binding sites, and variations upon this mechanism, were fitted to data using a maximum likelihood method that uses the Hawkes-Jalali-Colquhoun (HJC) treatment of missed brief events. The mutant receptor produced prolonged activations, bursts of openings that cause a slow decay of simulated synaptic currents. The main reason for the longer bursts of openings seen with mutant receptor was a decrease in the rate of ACh dissociation from diliganded receptors, though the lifetime of individual openings was somewhat increased too. As well as producing long bursts, the mutant receptor also produced many very short openings, though these carry little current. The burst structure for the mutant receptor at low ACh concentration is unusual in that most long bursts appear to start in a very brief monoliganded open state that then usually binds another ACh molecule to produce a long diliganded activation. The first opening is so short that it will usually be missed (together with the shut time that follows it), so the true burst length is likely to be underestimated.

Acetylcholine↗

PubMed1997

Modeling two-state disease processes with random effects.

Many chronic medical conditions are manifested by alternating sojourns in symptom-free and symptomatic states. In many cases, in addition to their relapsing and remitting nature, these conditions lead to worsening disease patterns over time and may exhibit seasonal trends. We develop a mixed-effect two-state model for such disease processes in which covariate effects are modeled multiplicatively on transition intensities. The transition intensities, in turn, are functions of three time scales: the semi-Markov scale involving the backward recurrence time for the cyclical component, the Markov scale for the time trend component, and a seasonal time scale. Multiplicative bivariate log-normal random effects are introduced to accommodate heterogeneity in disease activity between subjects and to admit a possible negative correlation between the transition intensities. Maximum likelihood estimation is carried out using Gauss-Hermite integration and a standard Newton-Raphson procedure. Tests of homogeneity are presented based on score statistics. An application of the methodology to data from a multi-center clinical trial of chronic bronchitis is provided for illustrative purposes.

Anti-Infective Agents↗

PubMed1999

A stochastic self-organizing map for proximity data.

We derive an efficient algorithm for topographic mapping of proximity data (TMP), which can be seen as an extension of Kohonen's self-organizing map to arbitrary distance measures. The TMP cost function is derived in a Baysian framework of folded Markov chains for the description of autoencoders. It incorporates the data by a dissimilarity matrix D and the topographic neighborhood by a matrix H of transition probabilities. From the principle of maximum entropy, a nonfactorizing Gibbs distribution is obtained, which is approximated in a mean-field fashion. This allows for maximum likelihood estimation using an expectation-maximization algorithm. In analogy to the transition from topographic vector quantization to the self-organizing map, we suggest an approximation to TMP that is computationally more efficient. In order to prevent convergence to local minima, an annealing scheme in the temperature parameter is introduced, for which the critical temperature of the first phase transition is calculated in terms of D and H. Numerical results demonstrate the working of the algorithm and confirm the analytical results. Finally, the algorithm is used to generate a connection map of areas of the cat's cerebral cortex.

Algorithms↗