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PubMed2004

Parametric inference for biological sequence analysis.

One of the major successes in computational biology has been the unification, by using the graphical model formalism, of a multitude of algorithms for annotating and comparing biological sequences. Graphical models that have been applied to these problems include hidden Markov models for annotation, tree models for phylogenetics, and pair hidden Markov models for alignment. A single algorithm, the sum-product algorithm, solves many of the inference problems that are associated with different statistical models. This article introduces the polytope propagation algorithm for computing the Newton polytope of an observation from a graphical model. This algorithm is a geometric version of the sum-product algorithm and is used to analyze the parametric behavior of maximum a posteriori inference calculations for graphical models.

Algorithms↗
PubMed2001

The Rasch model, additive conjoint measurement, and new models of probabilistic measurement theory.

This research describes some of the similarities and differences between additive conjoint measurement (a type of fundamental measurement) and the Rasch model. It seems that there are many similarities between the two frameworks, however, their differences are nontrivial. For instance, while conjoint measurement specifies measurement scales using a data-free, non-numerical axiomatic frame of reference, the Rasch model specifies measurement scales using a numerical frame of reference that is, by definition, data dependent. In order to circumvent difficulties that can be realistically imposed by this data dependence, this research formalizes new non-parametric item response models. These models are probabilistic measurement theory models in the sense that they explicitly integrate the axiomatic ideas of measurement theory with the statistical ideas of order-restricted inference and Markov Chain Monte Carlo. The specifications of these models are rather flexible, as they can represent any one of several models used in psychometrics, such as Mokken's (1971) monotone homogeneity model, Scheiblechner's (1995) isotonic ordinal probabilistic model, or the Rasch (1960) model. The proposed non-parametric item response models are applied to analyze both real and simulated data sets.

Humans↗
PubMedDate not supplied

CAN'T MISS--conquer any number task by making important statistics simple. Part 1. Types of variables, mean, median, variance, and standard deviation.

Healthcare quality improvement professionals need to understand and use inferential statistics to interpret sample data from their organizations. In quality improvement and healthcare research studies all the data from a population often are not available, so investigators take samples and make inferences about the population by using inferential statistics. This three-part series will give readers an understanding of the concepts of inferential statistics as well as the specific tools for calculating confidence intervals for samples of data. This article, Part 1, presents basic information about data including a classification system that describes the four major types of variables: continuous quantitative variable, discrete quantitative variable, ordinal categorical variable (including the binomial variable), and nominal categorical variable. A histogram is a graph that displays the frequency distribution for a continuous variable. The article also demonstrates how to calculate the mean, median, standard deviation, and variance for a continuous variable.

Analysis of Variance↗
PubMedDate not supplied

CAN'T MISS--conquer any number task by making important statistics simple. Part 2. Probability, populations, samples, and normal distributions.

Healthcare quality improvement professionals need to understand and use inferential statistics to interpret sample data from their organizations. In quality improvement and healthcare research studies all the data from a population often are not available, so investigators take samples and make inferences about the population by using inferential statistics. This three-part series will give readers an understanding of the concepts of inferential statistics as well as the specific tools for calculating confidence intervals for samples of data. This article, Part 2, describes probability, populations, and samples. The uses of descriptive and inferential statistics are outlined. The article also discusses the properties and probability of normal distributions, including the standard normal distribution.

Data Interpretation, Statistical↗
PubMedDate not supplied

CAN'T MISS--conquer any number task by making important statistics simple. Part 3. Standard error, estimation, and confidence intervals.

Healthcare quality improvement professionals need to understand and use inferential statistics to interpret sample data from their organizations. In quality improvement and healthcare research studies all the data from a population often are not available, so investigators take samples and make inferences about the population by using inferential statistics. This three-part series will give readers an understanding of the concepts of inferential statistics as well as the specific tools for calculating confidence intervals for samples of data. This article, Part 3, describes standard error and margin of error for a continuous variable and how they are calculated from the sample size and standard deviation of a sample. The article then demonstrates how the standard error and margin of error are used to calculate the confidence interval for estimating a population mean based on a sample mean.

Analysis of Variance↗
PubMed1992

Epidemiology of pediatric trauma: importance of population-based statistics.

To determine the validity of using hospital-based pediatric trauma registry data to draw specific inferences with regard to regional pediatric trauma system design, we compared statistical data on the incidence and mortality of pediatric and adult injuries and burns calculated by the New York State Department of Health, based on legally mandated reports of injury deaths and hospital discharges for 1989. During this year, some 488 children, aged 0 to 14 years, died as a result of injuries, a rate of 13.8 per 100,000 annually, of whom 408 (11.6/100,000) died as a result of traumatic injuries or burns, a population-based rate 20% of that observed in adults. During the same period, 16,402 children were hospitalized for treatment of traumatic injuries and burns, a rate of 465 per 100,000 annually, a population-based rate 56% of that observed in adults; and of this number, some 90 children died, yielding an in-hospital mortality "rate" (ie, case fatality ratio) of 0.55%, and a population-based rate of 2.6 per 100,000 annually. Thus, 9.0 of the 11.6 per 100,000 children who died in New York State in 1989 as a result of traumatic injuries and burns were not admitted to the hospital and, therefore, were unknown to the statewide hospital reporting system.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic↗
PubMed2002

Inferring relationships between pairs of individuals from locus heterozygosities.

BACKGROUND: The traditional exact method for inferring relationships between individuals from genetic data is not easily applicable in all situations that may be encountered in several fields of applied genetics. This study describes an approach that gives affordable results and is easily applicable; it is based on the probabilities that two individuals share 0, 1 or both alleles at a locus identical by state. RESULTS: We show that these probabilities (zi) depend on locus heterozygosity (H), and are scarcely affected by variation of the distribution of allele frequencies. This allows us to obtain empirical curves relating zi's to H for a series of common relationships, so that the likelihood ratio of a pair of relationships between any two individuals, given their genotypes at a locus, is a function of a single parameter, H. Application to large samples of mother-child and full-sib pairs shows that the statistical power of this method to infer the correct relationship is not much lower than the exact method. Analysis of a large database of STR data proves that locus heterozygosity does not vary significantly among Caucasian populations, apart from special cases, so that the likelihood ratio of the more common relationships between pairs of individuals may be obtained by looking at tabulated zi values. CONCLUSIONS: A simple method is provided, which may be used by any scientist with the help of a calculator or a spreadsheet to compute the likelihood ratios of common alternative relationships between pairs of individuals.

DNA Fingerprinting↗
PubMed2006

The multiscale character of evoked cortical activity.

Both the architecture and the dynamics of the brain have characteristic features at different spatial scales. However, the existence, nature and function of dynamical interdependencies between such scales have not been investigated. We studied the multiscale properties of functional magnetic resonance imaging (fMRI) data acquired while human subjects viewed a visual image. Traditional "region of interest" analysis of this data set revealed evoked activity in primary and extrastriate visual cortex. Wavelet transform in the spatial domain provides a multiscale representation of this evoked brain activity. Studying the correlation structure of this representation revealed strong and novel interdependencies in these data within and between different spatial scales. We found that such correlations are stronger than those evident in the original data and comparable in magnitude to those obtained after Gaussian smoothing. However, analysis of the data in the wavelet domain revealed additional structure such as positive correlations, strong anti-correlations and phase-lagged interdependencies. Statistical significance of these effects was inferred through nonparametric bootstrap techniques. We conclude that the spatial analysis of functional neuroimaging data in the wavelet domain provides novel information which may reflect complex spatiotemporal neuronal activity and information encoding. It also affords a quantitative means of testing hierarchical and multiscale models of cortical activity.

Adult↗
PubMed2001

A method for making group inferences from functional MRI data using independent component analysis.

Independent component analysis (ICA) is a promising analysis method that is being increasingly applied to fMRI data. A principal advantage of this approach is its applicability to cognitive paradigms for which detailed models of brain activity are not available. Independent component analysis has been successfully utilized to analyze single-subject fMRI data sets, and an extension of this work would be to provide for group inferences. However, unlike univariate methods (e.g., regression analysis, Kolmogorov-Smirnov statistics), ICA does not naturally generalize to a method suitable for drawing inferences about groups of subjects. We introduce a novel approach for drawing group inferences using ICA of fMRI data, and present its application to a simple visual paradigm that alternately stimulates the left or right visual field. Our group ICA analysis revealed task-related components in left and right visual cortex, a transiently task-related component in bilateral occipital/parietal cortex, and a non-task-related component in bilateral visual association cortex. We address issues involved in the use of ICA as an fMRI analysis method such as: (1) How many components should be calculated? (2) How are these components to be combined across subjects? (3) How should the final results be thresholded and/or presented? We show that the methodology we present provides answers to these questions and lay out a process for making group inferences from fMRI data using independent component analysis.

Algorithms↗
PubMed2000

Assessment of soft tissue facial asymmetry in medically normal and syndrome-affected individuals by analysis of landmarks and measurements.

We investigated soft tissue facial asymmetry in normal and syndrome-affected individuals ranging in age from 1 year to adulthood. The purposes of our study were to determine if facial asymmetry was greater in syndrome-affected individuals than in normal individuals and, if true, to distinguish those measurements that could be used in routine screening to identify the presence of syndromes in uncertain patients and, lastly, to investigate the causes of measurement asymmetry at the level of the landmarks. The last purpose was possible because we used a stereophotogrammetric method with which the three-dimensional (3D) landmark positions were obtained. In the statistically significantly different measurements, those from the right side were dominant, with one exception in each group, except normal males. In all groups the landmark analyses demonstrated the same trends, and while there was far less patterning in the 3D coordinates, these results were also consistent between the four groups. We compared the statistical findings of the 3D coordinates and measurements and found that there was no predictable relationship between significant findings in the landmarks and the measurements. In particular, we noted that statistical differences in measurements did not infer significant differences in the positions of the landmarks between the right and left sides of the face. Both the normal and syndrome-affected groups appeared to be equally canalized and similarly affected by developmental noise: When the bilateral measurement differences of each syndrome-affected subject were compared to the limits of normal asymmetry, less than 10% of the comparisons exceeded the norms.

Adolescent↗
PubMed2005

Semiparametric methods for mapping quantitative trait loci with censored data.

Statistical methods for the detection of genes influencing quantitative traits with the aid of genetic markers are well developed for normally distributed, fully observed phenotypes. Many experiments are concerned with failure-time phenotypes, which have skewed distributions and which are usually subject to censoring because of random loss to follow-up, failures from competing causes, or limited duration of the experiment. In this article, we develop semiparametric statistical methods for mapping quantitative trait loci (QTLs) based on censored failure-time phenotypes. We formulate the effects of the QTL genotype on the failure time through the Cox (1972, Journal of the Royal Statistical Society, Series B 34, 187-220) proportional hazards model and derive efficient likelihood-based inference procedures. In addition, we show how to assess statistical significance when searching several regions or the entire genome for QTLs. Extensive simulation studies demonstrate that the proposed methods perform well in practical situations. Applications to two animal studies are provided.

Animals↗
PubMed1995

Depolarizing GABA-activated Cl- channels in embryonic rat spinal and olfactory bulb cells.

1. We have compared the electrical properties of the Cl- channels activated by GABA in cells acutely dissociated from embryonic (E) spinal cord (SC) and olfactory bulb (OB) regions at E15 using different configurations of the patch-recording technique. By in situ analysis these cells express GABAA receptor mRNAs encoding a common set of subunits (alpha 2, beta 2, and beta 3). SC cells also express alpha 3, alpha 5 and gamma 2s transcripts. 2. Whole-cell recordings revealed current responses to GABA (0.5 microM to 1 mM) in 242 out of 294 cells. In both SC and OB cells, currents evoked by 2 microM GABA could be potentiated by diazepam (DZP) in a dose-dependent manner with an EC50 of approximately 50 nM in both SC and OB. The maximal effect was approximately 300%. Both SC and OB cells exhibited GABA-activated currents that were only partially sensitive to zinc even at high micromolar concentrations. The effect of DZP and the relatively modest sensitivity to zinc suggest the presence of gamma subunits in both preparations. 3. Spectral analysis of current responses in twenty-six cells showed that power spectra could be fitted by three exponential components (tau 1-3) in the cells of both areas. The tau of the longest-lasting component (tau 3) was significantly different in the cells of the two areas: approximately 50 ms in OB and 80-100 ms in SC. No statistically significant differences in the average inferred unitary conductance between the two cell types could be resolved. 4. Single-channel properties were examined directly using the cell-attached configuration. GABA-activated channels could be recorded in only 89 out of well-sealed 984 patches and most of them exhibited multiple channel activity. The mean open time in the response to 10 microM GABA was significantly shorter in OB cells (12 ms) compared to SC cells (25 ms) while the average conductance values were not significantly different between the two cell types. 5. On average, Cl- channels reversed polarity when the on-cell patch pipette potential was approximately -30 mV. Thus, in these embryonic neurons, micromolar GABA activates Cl- channels, which, when open, effectively depolarize cells by approximately 30 mV. 6. Cl- channels activated by GABA are open longer in embryonic SC cells than in OB cells. This statistically significant difference in native GABAA receptor Cl- channel properties correlates with, and may be related to differences in subunit mRNA expression.

Action Potentials↗
PubMed2003

Statistical characterization of ion trap tandem mass spectra from doubly charged tryptic peptides.

Collision-induced dissociation (CID) is a common ion activation technique used to energize mass-selected peptide ions during tandem mass spectrometry. Characteristic fragment ions form from the cleavage of amide bonds within a peptide undergoing CID, allowing the inference of its amino acid sequence. The statistical characterization of these fragment ions is essential for improving peptide identification algorithms and for understanding the complex reactions taking place during CID. An examination of 1465 ion trap spectra from doubly charged tryptic peptides reveals several trends important to understanding this fragmentation process. While less abundant than y ions, b ions are present in sufficient numbers to aid sequencing algorithms. Fragment ions exhibit a characteristic series-specific relationship between their masses and intensities. Each residue influences fragmentation at adjacent amide bonds, with Pro quantifiably enhancing cleavage at its N-terminal amide bond and His increasing the formation of b ions at its C-terminal amide bond. Fragment ions corresponding to a formal loss of ammonia appear preferentially in peptides containing Gln and Asn. These trends are partially responsible for the complexity of peptide tandem mass spectra.

Mass Spectrometry↗
PubMed2006

Prediction of recurrent spontaneous pneumothorax: CT scan findings versus management features.

OBJECTIVE: To assess the association between primary spontaneous pneumothorax (PSP) recurrence and pulmonary CT scan findings, and other variables pertaining to clinical presentation and management. METHODS: Consecutive patients hospitalized for the first episode of PSP and treated by various strategies including chest tube or pleurocatheter drainage and, in persistent pneumothorax, by chemical or surgical pleurodesis. All patients had a pulmonary CT scan examination in the week following hospital discharge in order to calculate a score combining distribution, number and size of dystrophic pulmonary abnormalities. This score as well as other pertinent clinical and therapeutic parameters were compared between patients who ultimately experienced PSP recurrence and those who did not. RESULTS: Eighty patients (mean age: 27+/-7 yr) were admitted for PSP and had a chest drainage with either a drain or pleurocatheter. Chest drainage and hospitalization durations were 4.7+/-3.2 and 6.2+/-3.5 days, respectively. Sixteen patients required chemical pleurodesis. Dystrophic bullae were present in CT scans in 72.5% patients. After a mean follow up of 34+/-20 months, 15 out of the 80 patients (19%) had a PSP recurrence. Multivariate statistical analysis disclosed the use of pleurocatheter (OR=5; 95% CI: 1.4-20; P=0.02) and of chemical pleurodesis (OR=8; 95% CI: 1.5-47; P=0.015) as independent predictors of PSP recurrence. The severity of dystrophic lesions inferred from the dystrophic score was not statistically associated with the risk of recurrence. CONCLUSION: Dystrophic lesions are frequently present in PSP. They are not associated with an increased risk of recurrence.

Adolescent↗
PubMed1987

Discrimination of DNA ploidy patterns by order statistics.

The use of order statistics to discriminate and classify DNA ploidy patterns is proposed, especially for the classification of additional observations: whether a given sample is more likely to have come from a normal or an abnormal tissue, and with what probability, based on its ploidy pattern. The method involves the order of observations within each of several samples (e.g., euploid and aneuploid DNA patterns) and the use of subsets of the obtained order statistics as independent variables in a linear discriminant analysis. It thus replaces univariate observations by (some of) their order statistics, which are then used as the variables in the discriminant analysis. The procedure does not require normality of distributions or the transformation of nonnormal distributions, as do many discriminant functions; order statistics are usually distribution-free and thus are particularly useful for nonparametric inference. Preliminary simulation studies verified the potential usefulness of the order statistics discriminant function method as applied to DNA ploidy analysis. Its advantages as compared to the usual methods for hypothesis testing, e.g., the use of the chi-square or Kolmogorov-Smirnov tests to as certain "goodness-of-fit," is discussed. The proposed method is easy to implement and easy to interpret; it is also applicable to the study of distributions of other types of measurements.

Biometry↗
PubMed1999

Prescribed daily doses and 'risk factors' associated with the use of benzodiazepines in primary care.

OBJECTIVE: To assess the extent, characteristics and determinants of benzodiazepine prescription in outpatient Primary Health Care. METHODS: A clinical audit of a stratified random sample of Primary Health Care Centres in the seven islands and 1.6 million inhabitants region of 'Canarias' in Spain was carried out. From those centres, a random sample of 1045 clinical records was reviewed and information on diagnosis, prescription and prescribed dosages was collected in a structured questionnaire. A multivariate logistic regression analysis was performed in order to determine the 'risk factors' for the use of benzodiazepines. RESULTS: Benzodiazepine prescription was recorded in 23.4% of all clinical records; 87.7% of these were for benzodiazepines classified as anxiolytics (N05B) and 12.3% for hypnotics (N05C2). Benzodiazepine prescription was more common for women, elderly, widowed, divorced, low educational background, housewives and retired people. Using multivariate logistic regression, the probability of benzodiazepine prescription was found to be closely related to age, gender and employment status, but not with educational level. Prescribed Daily Doses were lower than Defined Daily Doses (DDD) in 77.1% of all anxiolytic prescriptions, but were in agreement with DDD in 90% of hypnotic prescriptions. The duration of treatment recorded in the clinical records was 25+/-21 months, with a range of 1 and 144 months. General Practitioners were responsible for 67% of all benzodiazepine prescription. Anxiolytics were prescribed as a single daily dose in 57% of the cases, and only 'at supper' in 48.6%. CONCLUSION: In the general population attending Primary Health Care Centres of the Canary Islands Health System the prescription of benzodiazepines is higher for women and the elderly, and the most common use is chronic, with a duration of over 2 years in most cases. Anxiolytics are prescribed in doses which are much lower than those used as DDD and were used only 'at night' in almost half of the cases. This could represent an overlapping of the indications with hypnotics, and explain part of the huge difference in the use of anxiolytics in Spain compared with other figures in Europe. This fact must also be taken into account when making inferences of benzodiazepine use from sales statistics, which are very imprecise measures of drug use.

Journal Article↗
PubMed2006

Permutation testing of orthogonal factorial effects in a language-processing experiment using fMRI.

The block-paradigm of the Functional Image Analysis Contest (FIAC) dataset was analysed with the Brain Activation and Morphological Mapping software. Permutation methods in the wavelet domain were used for inference on cluster-based test statistics of orthogonal contrasts relevant to the factorial design of the study, namely: the average response across all active blocks, the main effect of speaker, the main effect of sentence, and the interaction between sentence and speaker. Extensive activation was seen with all these contrasts. In particular, different vs. same-speaker blocks produced elevated activation in bilateral regions of the superior temporal lobe and repetition suppression for linguistic materials (same vs. different-sentence blocks) in left inferior frontal regions. These are regions previously reported in the literature. Additional regions were detected in this study, perhaps due to the enhanced sensitivity of the methodology. Within-block sentence suppression was tested post-hoc by regression of an exponential decay model onto the extracted time series from the left inferior frontal gyrus, but no strong evidence of such an effect was found. The significance levels set for the activation maps are P-values at which we expect <1 false-positive cluster per image. Nominal type I error control was verified by empirical testing of a test statistic corresponding to a randomly ordered design matrix. The small size of the BOLD effect necessitates sensitive methods of detection of brain activation. Permutation methods permit the necessary flexibility to develop novel test statistics to meet this challenge.

Algorithms↗
PubMed2004

Parametric modelling of cost data in medical studies.

The cost of medical resources used is often recorded for each patient in clinical studies in order to inform decision-making. Although cost data are generally skewed to the right, interest is in making inferences about the population mean cost. Common methods for non-normal data, such as data transformation, assuming asymptotic normality of the sample mean or non-parametric bootstrapping, are not ideal. This paper describes possible parametric models for analysing cost data. Four example data sets are considered, which have different sample sizes and degrees of skewness. Normal, gamma, log-normal, and log-logistic distributions are fitted, together with three-parameter versions of the latter three distributions. Maximum likelihood estimates of the population mean are found; confidence intervals are derived by a parametric BC(a) bootstrap and checked by MCMC methods. Differences between model fits and inferences are explored.Skewed parametric distributions fit cost data better than the normal distribution, and should in principle be preferred for estimating the population mean cost. However for some data sets, we find that models that fit badly can give similar inferences to those that fit well. Conversely, particularly when sample sizes are not large, different parametric models that fit the data equally well can lead to substantially different inferences. We conclude that inferences are sensitive to choice of statistical model, which itself can remain uncertain unless there is enough data to model the tail of the distribution accurately. Investigating the sensitivity of conclusions to choice of model should thus be an essential component of analysing cost data in practice.

Clinical Trials as Topic↗