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PubMedDate not supplied

Analyzing red blood cell-deformability distributions.

BACKGROUND: Red blood cells (RBCs) must deform to pass the smallest capillaries of the microcirculation. Available techniques for measuring RBC deformability often provide an indication of the mean deformability. The latter may be decreased either by a slight overall deformability reduction or by the presence of a small fraction of rigid cells. A distinction between these two cases can be made with a RBC-deformability distribution (RBC-DD). METHODS: This paper explores RBC-DDs of healthy individuals and of cells with anomalous mechanical properties (sickle cell disease, dialysis patients, elliptocytosis, and cultivated malaria tropica). The distributions were measured with an automated rheoscope, which uses advanced image analysis techniques to obtain the deformability index of a large number of individual cells subjected to simple shear flow. RESULTS: The RBC-DD of healthy volunteers is close to a normal distribution. In the investigated patients, distributions were markedly different and yielded significant changes in the mean, in the standard deviation, or in both. The presence of hypodeformable and hyperdeformable cell fractions can qualitatively and quantitatively be assessed from the deformability distribution (DD). In elliptocytosis, cells orient differently with respect to the streamlines, compared to normal cells. This causes the DD to be biased. CONCLUSIONS: The RBC-DD is a powerful representation to establish subpopulations with anomalous deformability. Fractions of hypodeformable and hyperdeformable cells and the standard deviation of the DD are new and excellent quantitative parameters to assess alterations in RBC deformability.

Anemia, Sickle Cell↗
PubMed2004

Exercise capacity and heart rate recovery as predictors of coronary heart disease events, in patients with heterozygous Familial Hypercholesterolemia.

BACKGROUND: Several clinical and observational studies have established that exercise capacity and activity status are strong predictors of cardiovascular and overall mortality. We aimed to evaluate the relationship between exercise tolerance test (ETT) indices and occurrence of coronary heart disease (CHD), in patients with heterozygous Familial Hypercholesterolemia (eFH). METHODS: During 1987-1997, we enrolled 639 cardiovascular disease-free patients with heterozygous eFH; 58 (9%) patients were excluded since they had a positive ETT. A fatal or non-fatal CHD event was the end point. Cox proportional hazards models were applied to evaluate the association between the investigated outcome and ETT indices. RESULTS: During the follow-up (1987-2002), 53 (18%) men and 34 (10%) women developed a CHD event (11 were fatal). The age-adjusted event rate was 87 events per 2915 person-years (3%). Statistical analysis revealed that exercise capacity (hazard ratio = 0.82, P < 0.001), heart rate recovery at 1 min (hazard ratio = 0.91, P < 0.05), and peak pulse pressure levels (hazard ratio = 1.03, P < 0.001), were predictors of CHD, after controlling for several potential confounders. CONCLUSION: Decreased exercise capacity, a delayed decrease in heart rate during the first minute of graded exercise, and increased peak pulse pressure are strong predictors of coronary events in patients with eFH. Physical activity should be strongly recommended in these patients.

Adult↗
PubMed1994

Computational DNA sequence analysis.

This paper reviews several new developments in computer and statistical analysis of DNA and protein sequences. We present criteria and describe means for assessing and interpreting genomic inhomogeneities within and between sequences. These include: (a) characterizations of short oligonucleotide biases and general compositional tendencies; (b) molecular evolutionary reconstructions based on dinucleotide relative abundance distance measures and partial orderings; and (c) the application of r-scan statistics, quantile distributions, and score-based analyses to identify clustering, overdispersion, and excessive evenness in the distribution of a marker array along a sequence. These apply, for example, to restriction sites, microsatellite runs, regulatory motifs, and nucleosome placements. Furthermore, (d) the definition and determination of rare and frequent oligonucleotides and peptides provides another perspective on sequence heterogeneity, and (e) score methods are also applied in exon and gene locations. Most of the ideas and methods are illustrated with respect to bacteriophage genomes, to megabase amounts of several eukaryotic sequences, to a diverse collection of bacterial sets, to mitochondrial chromosomes, and to a broad assembly of viral genomes.

Amino Acid Sequence↗
PubMedDate not supplied

Anterior knee pain after intramedullary nailing of a tibial shaft fracture: an ultrasound study of the patellar tendons of 36 patients.

OBJECTIVES: Chronic anterior knee pain is a common complication following intramedullary nailing of a tibial shaft fracture. The etiology of pain is often not known. This study sonographically examined the patellar tendons of patients with a nailed tibial shaft fracture. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Fifty consecutive patients with a nailed tibial shaft fracture were initially included in the study. Thirty-six of them could be measured at an average of 2.5 +/- 0.5 years after nail insertion (1.0 +/- 0.3 years after nail extraction). INTERVENTION: Reamed intramedullary nailing with 2 interlocking bolts at both ends of the nail (Grosse-Kempf-nail, Howmedica). MAIN OUTCOME MEASUREMENTS: The ultrasound investigation of the patellar tendons of the 36 patients. RESULTS: Twelve (33%) patients were painless and 24 (67%) patients had anterior knee pain at follow-up. With the reference to the mean difference in the thickness of the distal part of the patellar tendon in the operated limb versus nonoperated limb, the result was 1.4 +/- 1.1 mm in the chronic pain group and 2.6 +/- 2.5 mm in the painless group (P = 0.135, [95% confidence interval for the group difference = -0.4-2.8]). The corresponding values for the proximal part of the patellar tendon was 1.4 +/- 1.3 mm in the chronic pain group and 2.3 +/- 2.3 mm in the painless group (P = 0.251, [95% confidence interval for the group difference = -0.7-2.4]). There were no statistically significantly differences between study groups in the blood circulation of the patellar tendon or at the entry point, calcification of the patellar tendon, granulation tissue at the entry point, or occurrence of low echo areas in the patellar tendon. CONCLUSION: After intramedullary nailing of a tibial shaft fracture, patients with or without anterior knee pain show similar changes in the ultrasound investigation of their patellar tendons. Based on those findings, it does not appear to make any difference as to the approach used (paratendinous or transtendinous) for intramedullary nailing of the tibia.

Adult↗
PubMed2000

Modeling pharmacokinetic data using heavy-tailed multivariate distributions.

Pharmacokinetic studies of drug and metabolite concentrations in the blood are usually conducted as crossover trials, especially in Phases I and II. A longitudinal series of measurements is collected on each subject within each period. Dependence among such observations, within and between periods, will generally be fairly complex, requiring two levels of variance components, for the subjects and for the periods within subjects, and an autocorrelation within periods as well as a time-varying variance. Until now, the standard way in which this has been modeled is using a multivariate normal distribution. Here, we introduce procedures for simultaneously handling these various types of dependence in a wider class of distributions called the multivariate power exponential and Student t families. They can have the heavy tails required for handling the extreme observations that may occur in such contexts. We also consider various forms of serial dependence among the observations and find that they provide more improvement to our models than do the variance components. An integrated Ornstein-Uhlenbeck (IOU) stochastic process fits much better to our data set than the conventional continuous first-order autoregression, CAR(1). We apply these models to a Phase I study of the drug, flosequinan, and its metabolite.

Clinical Trials, Phase I as Topic↗
PubMed2005

The probability distribution for a random match between an experimental-theoretical spectral pair in tandem mass spectrometry.

Proteomic techniques are fast becoming the main method for qualitative and quantitative determination of the protein content in biological systems. Despite notable advances, efficient and accurate analysis of high throughput proteomic data generated by mass spectrometers remains one of the major stumbling blocks in the protein identification problem. We present a model for the number of random matches between an experimental MS-MS spectrum and a theoretical spectrum of a peptide. The shape of the probability distribution is a function of the experimental accuracy, the number of peaks in the experimental spectrum, the length of the interval over which the peaks are distributed, and the number of theoretical spectral peaks in this interval. Based on this probability distribution, a goodness-of-fit tool can be used to yield fast and accurate scoring schemes for peptide identification through database search. In this paper, we describe one possible implementation of such a method and compare the performance of the resulting scoring function with that of SEQUEST. In terms of speed, our algorithm is roughly two orders of magnitude faster than the SEQUEST program, and its accuracy of peptide identification compares favorably to that of SEQUEST. Moreover, our algorithm does not use information related to the intensities of the peaks.

Algorithms↗
PubMedDate not supplied

Statistical evaluation of geochemical parameter distribution in a ground water system contaminated with petroleum hydrocarbons.

A shallow-depth ground water area was investigated to identify the dominant processes governing the distribution of hydrocarbon contaminants and hydrogeochemical parameters. The ground water in the study site has been highly contaminated with petroleum hydrocarbons. A preliminary pump-and-treatment remediation technology was applied for 4 yr at the site. Multivariate analyses were applied to hydrogeochemical data obtained before and after the rainy season. The pump-and-treatment application, indigenous biodegradation, and mixing by precipitation recharge are the major factors or events involved in the distribution of geochemical parameters of the ground water in the study area. Site-specific artificial pavement also played an important role in the evolution of the ground water chemistry. A conventional graphical analysis method (Piper plot) of major ions did not effectively reveal these effects. In this study, we demonstrate the usefulness of multivariate analysis (factor and cluster analyses) using biodegradation indicator parameters, as well as major cations and anions, for the study of the ground water system in the hydrocarbon-contaminated site.

Biodegradation, Environmental↗
PubMed2005

Moments of the Boltzmann distribution for RNA secondary structures.

We here present a dynamic programming algorithm which is capable of calculating arbitrary moments of the Boltzmann distribution for RNA secondary structures. We have implemented the algorithm in a program called RNA-variance and investigate the difference between the Boltzmann distribution of biological and random RNA sequences. We find that the minimum free energy structure of biological sequences has a higher probability in the Boltzmann distribution than random sequences. Moreover, we show that the free energies of biological sequences have a smaller variance than random sequences and that the minimum free energy of biological sequences is closer to the expected free energy of the rest of the structures than that of random sequences. These results suggest that biologically functional RNA sequences not only require a thermodynamically stable minimum free energy structure, but also an ensemble of structures whose free energies are close to the minimum free energy.

Algorithms↗
PubMed2003

Oesophageal perforation in preterm neonates: not an innocent bystander.

OBJECTIVE: To compare the clinical course and neonatal outcomes of preterm infants with oesophageal perforation (OP). METHODS: Retrospective case control study of infants admitted between 1994 and 2001 and diagnosed with OP was performed at two tertiary care centres in Toronto, Canada. One control per case was matched by the gestational age and the month of birth. Occurrence of air leak syndrome/pleural effusion requiring drainage, the duration of supplemental oxygen and the time to attain full feeds were compared. RESULTS: Ten cases of OP were identified. The commonest clinical presentation was air leak syndrome/pleural effusion. There was a statistically significant increase in the time to attain full enteral feeds in OP group (P = 0.02). The duration of supplemental oxygen was prolonged in infants with OP, however, this was statistically insignificant (P = 0.20). The infants were managed conservatively and perforation healed in all. CONCLUSION: Oesophageal perforation is a rare but important complication of modern neonatal intensive care setting. The diagnosis of OP should be considered in infants who present with sudden/acute deterioration in their respiratory status following procedures involving pharyngeal region. Conservative management in an otherwise uncomplicated case leads to complete recovery in neonates.

Case-Control Studies↗
PubMed1999

Sample size for comparing linear growth curves.

Assuming a linear growth curve model under a suitable link function, we compute the sample size for comparing two treatment groups when the repeated measurements marginally follow exponential family distributions. From the treatment profiles of the chosen link function, we compute the common intercept beta0 and the regression slopes beta1 and beta2 to define delta = beta1 - beta2, the difference to be detected, under a specified alternative hypothesis. The dispersion matrices of the generalized estimating equations estimators are obtained under the null and alternative hypotheses using a suitable working correlation matrix. We compute the sample size assuming that delta is asymptotically normal. Details are worked out for repeated measures designs with binary and count data along with numerical examples.

Female↗
PubMed2005

Discriminating between rate heterogeneity and interspecific recombination in DNA sequence alignments with phylogenetic factorial hidden Markov models.

MOTIVATION: A recently proposed method for detecting recombination in DNA sequence alignments is based on the combination of hidden Markov models (HMMs) with phylogenetic trees. Although this method was found to detect breakpoints of recombinant regions more accurately than most existing techniques, it inherently fails to distinguish between recombination and rate variation. In the present paper, we propose to marry the phylogenetic tree to a factorial HMM (FHMM). The states of the first hidden chain represent tree topologies, whereas the states of the second independent hidden chain represent different global scaling factors of the branch lengths. Inference is done in terms of a hierarchical Bayesian model, where parameters and hidden states are sampled from the posterior distribution with Gibbs sampling. RESULTS: We have tested the proposed model on various synthetic and real-world DNA sequence alignments. The simulation results suggest that as opposed to the standard phylogenetic HMM, the phylogenetic FHMM clearly distinguishes between recombination and rate heterogeneity and thereby avoids the prediction of spurious recombinant regions. AVAILABILITY: The proposed method has been implemented in a MATLAB package that extends Kevin Murphy's HMM toolbox. Software and data used in our study are available from http://www.bioss.sari.ac.uk/~dirk/Supplements

Algorithms↗
PubMed2005

Model-based segmentation of medical imagery by matching distributions.

The segmentation of deformable objects from three-dimensional (3-D) images is an important and challenging problem, especially in the context of medical imagery. We present a new segmentation algorithm based on matching probability distributions of photometric variables that incorporates learned shape and appearance models for the objects of interest. The main innovation over similar approaches is that there is no need to compute a pixelwise correspondence between the model and the image. This allows for a fast, principled algorithm. We present promising results on difficult imagery for 3-D computed tomography images of the male pelvis for the purpose of image-guided radiotherapy of the prostate.

Algorithms↗
PubMed2006

The relationship between migraine and atopic disorders-the contribution of pulmonary function tests and immunological screening.

This cross-sectional clinical study was conducted in order to explore the relationship between atopic disorders and migraine. We evaluated 186 consecutive patients with migraine. Patients with a history of atopic disorders were compared with the others during headache-free intervals, for their headache characteristics, pulmonary test (PFT) performances and immunological screenings, through appropriate statistical methods. Of the patients with migraine, 77 (41.4%) reported at least one atopic disorder. PFT screening showed a general decreased pulmonary capacity and an important correlation between a positive history of atopic disorders and both increased eosinophil and IgE levels in headache-free periods. It should be discussed whether screening with PFT or immunological tests helps in early detection of progressive lung disease which might develop in these patients.

Adolescent↗
PubMed2006

Structural diversity of protein segments follows a power-law distribution.

The local structures of protein segments were classified and their distribution was analyzed to explore the structural diversity of proteins. Representative proteins were divided into short segments using a sliding L-residue window. Each set of local structures consisting of consecutive 1-31 amino acids was classified using a single-pass clustering method. The results demonstrate that the local structures of proteins are very unevenly distributed in the protein universe. The distribution of local structures of relatively long segments shows a power-law behavior that is formulated well by Zipf's law, implying that a protein structure possesses recursive and fractal characteristics. The degree of effective conformational freedom per residue as well as the structure entropy per residue decreases gradually with an increasing value of L and then converges to constant values. This suggests that the number of protein conformations resides within the range between 1.2L and 1.5L and that 10- to 20-residue segments are already proteinlike in terms of their structural diversity.

Amino Acid Motifs↗
PubMedDate not supplied

[Ordering and temporal resolution in professional singers and in well tuned and out of tune amateur singers].

BACKGROUND: temporal ordering and temporal resolution. AIM: to compare the performance of professional singers with that of well tuned and out of tune amateur singers in the pitch pattern test (PPT) and in the Random Gap Detection Test (RGDT). METHOD: participants were 78 individuals, male and female, with ages ranging from 18 to 55 years. All of the participants were singers with normal hearing - previously assessed using pure tone and speech audiometry--and had no language, speech, voice or hearing complaints. Each individual answered a questionnaire concerning, among other subjects, perception about own voice when singing, number of years of professional singing, difficulties when singing new songs and number of years of music study. For the objective assessment the PPT and the RGDT were used in order to investigate temporal ordering and temporal resolution respectively. RESULTS: regarding the RGDT, there was no statistically significant difference between the groups and variables. As for the PPT, it was observed that professional singers presented a better performance, with statistic significance, when compared to well tuned amateur singers and these a better performance when compared to out of tune amateur singers. The performance in the PPT was related to specialized training and study of music theory. CONCLUSION: the RGDT did not prove to be a sensitive test to distinguish professional and amateur singers. On the other hand, the PPT did. The performance in the PPT reflects the number of years of specialized auditory training and music theory study.

Adolescent↗
PubMed2005

[Central and peripheral corneal pachymetry--standard evaluation with the Pentacam system].

BACKGROUND: Corneal thickness measurements are important in refractive surgery, for interpretation of IOP and in corneal diseases. The purpose of this study was to generate specific standard values for the Pentacam system and to investigate the influence of body size, body mass index, body weight, gender and refraction on central and peripheral corneal thickness for a more detailed characterization of the corneal anatomy. MATERIALS AND METHODS: The Pentacam system is based on a 180 degrees rotating computer-aided Scheimpflug camera, which generates reconstructions of the anterior segment from 12 to 50 single captures. The central corneal thickness was calculated from 25 single captures in both eyes of 182 normal Caucasian subjects (age: 18 - 83 years). The peripheral corneal thickness was measured within 3 mm distances at 0 degrees , 90 degrees , 180 degrees and 270 degrees . All subjects underwent an ophthalmological examination. Correlations between corneal thickness and body size, body mass index, body weight, gender and refraction were analyzed statistically by non-parametric tests. RESULTS: The mean central corneal thickness of all 364 eyes was 534 +/- 36 microm. Divided into sides it was the same, 534 +/- 36 microm, in the right and in the left eyes. The mean central corneal thickness for female subjects was 533 +/- 40 microm, for males it was 534 +/- 35 microm. Statistically there was no proof of any dependence of the central corneal thickness values on the sides, gender, age, height, body mass index (BMI) or refraction. However, there was a positive significant correlation between central corneal thickness and body weight. The peripheral corneal thickness values were lowest in the temporal and inferior areas and greatest in the superior and in the nasal areas. In the superior and in the nasal areas there was a statistically significant negative correlation between age and peripheral corneal thickness. CONCLUSIONS: The corneal thickness can be measured touchless with the Pentacam system. The central corneal thickness seems to be correlated with the body weight. Anatomical features lead to lower peripheral corneal thickness values in the temporal and inferior areas than in the nasal and superior areas. In the nasal and in the superior areas the corneal thickness seems to decrease with age. Further trials are necessary to confirm these findings and to evaluate the precision, reproducibilitiy and independence of investigators of the corneal pachymetry with the Pentacam system.

Adolescent↗
PubMed2005

Dynamic Monte Carlo study on the probability distribution functions of tail-like polymer chain.

The configurational properties of tail-like polymer chains with one end attached to a flat surface are studied by using dynamic Monte Carlo technique. We find that the probability distribution of the free end in z direction P(R(z)) and the density profile rho(z) can be scaled approximately by a factor beta to be a length independent function for both random walking (RW) and self-avoiding walking (SAW) tail-like chains, where the factor beta is related to the mean square end-to-end distance . The scaled P(R(z)) of the SAW chain roughly overlaps that of the RW chain, but the scaled rho(z) of the SAW chain locates at smaller betaz than that of the RW chain.

Computer Simulation↗
PubMed2005

Parametric versus non-parametric statistics in the analysis of randomized trials with non-normally distributed data.

BACKGROUND: It has generally been argued that parametric statistics should not be applied to data with non-normal distributions. Empirical research has demonstrated that Mann-Whitney generally has greater power than the t-test unless data are sampled from the normal. In the case of randomized trials, we are typically interested in how an endpoint, such as blood pressure or pain, changes following treatment. Such trials should be analyzed using ANCOVA, rather than t-test. The objectives of this study were: a) to compare the relative power of Mann-Whitney and ANCOVA; b) to determine whether ANCOVA provides an unbiased estimate for the difference between groups; c) to investigate the distribution of change scores between repeat assessments of a non-normally distributed variable. METHODS: Polynomials were developed to simulate five archetypal non-normal distributions for baseline and post-treatment scores in a randomized trial. Simulation studies compared the power of Mann-Whitney and ANCOVA for analyzing each distribution, varying sample size, correlation and type of treatment effect (ratio or shift). RESULTS: Change between skewed baseline and post-treatment data tended towards a normal distribution. ANCOVA was generally superior to Mann-Whitney in most situations, especially where log-transformed data were entered into the model. The estimate of the treatment effect from ANCOVA was not importantly biased. CONCLUSION: ANCOVA is the preferred method of analyzing randomized trials with baseline and post-treatment measures. In certain extreme cases, ANCOVA is less powerful than Mann-Whitney. Notably, in these cases, the estimate of treatment effect provided by ANCOVA is of questionable interpretability.

Analysis of Variance↗