Effect of nonnormal random components on level and power in group-randomized trials

The use of group-randomized trials is particularly widespread in the evaluation of health care, educational, and screening strategies. Group-randomized trials represent a subset of a larger class of designs often labeled nested, hierarchical, or multilevel and are characterized by the randomization of intact social units or groups, rather than individuals. The application of random effects models to group-randomized trials requires the specification of fixed and random components of the model. The underlying assumption is usually that these random components are normally distributed. This research is intended to determine if the Type I error rate and power are affected when the assumption of normality for the random component representing the group effect is violated. ^ In this study, simulated data are used to examine the Type I error rate, power, bias and mean squared error of the estimates of the fixed effect and the observed intraclass correlation coefficient (ICC) when the random component representing the group effect possess distributions with non-normal characteristics, such as heavy tails or severe skewness. The simulated data are generated with various characteristics (e.g. number of schools per condition, number of students per school, and several within school ICCs) observed in most small, school-based, group-randomized trials. The analysis is carried out using SAS PROC MIXED, Version 6.12, with random effects specified in a random statement and restricted maximum likelihood (REML) estimation specified. The results from the non-normally distributed data are compared to the results obtained from the analysis of data with similar design characteristics but normally distributed random effects. ^ The results suggest that the violation of the normality assumption for the group component by a skewed or heavy-tailed distribution does not appear to influence the estimation of the fixed effect, Type I error, and power. Negative biases were detected when estimating the sample ICC and dramatically increased in magnitude as the true ICC increased. These biases were not as pronounced when the true ICC was within the range observed in most group-randomized trials (i.e. 0.00 to 0.05). The normally distributed group effect also resulted in bias ICC estimates when the true ICC was greater than 0.05. However, this may be a result of higher correlation within the data. ^

Stable isotope composition of carbonate components of Rhaetian shallow-water limestones of the Wombat Plateau

Stable oxygen- and carbon-isotope ratios of Rhaetian (upper Triassic) limestone samples from the Wombat Plateau, northwest Australia, were measured to explore possible diagenetic pathways that the material underwent after deposition in a shallow-water environment, before plateau submergence in the Early Cretaceous. Host sediment isotopic values cluster near typical marine carbonate values (d18O ranging from -2.57 per mil to +1.78 per mil and d13C, from +2.45 per mil to +4.01 per mil). Isotopic values of equant clear calcite lining or filling rock pores also plot in the field of marine cements (d18O = +1.59 per mil to -2.24 per mil and d13C = +4.25 per mil to +2.57 per mil), while isotopic values for neomorphic calcites replacing skeletal (megalodontid shell) carbonate material show a wider scatter of oxygen and carbon values, d18O ranging from +2.73 per milo to -6.2 per mil and d13C, from +5.04 per mil to +1.22 per mil. Selective dissolution of metastable carbonate phases (aragonite?) and neomorphic replacement of skeletal material probably occurred in a meteoric phreatic environment, although replacement products (inclusion-rich microspar, clear neomorphic spar, etc.) retained the original marine isotopic signature because transformation probably occurred in a closed system dominated by the composition of the dissolving phases (high rock/water ratio). The precipitation of late-stage equant (low-Mg?) calcite cement in the pores occurred in the presence of normal marine waters, probably in a deep-water environment, after plateau drowning. Covariance of d18O and d13C toward negative values indeed suggests influence of meteorically modified fluids. However, none of the samples shows negative carbon values, excluding the persistence of organic-rich soils on subaerial karstic surfaces (Caribbean-style diagenesis). Petrographical and geochemical data are consistent with the sedimentological evidence of plateau drowning in post-Rhaetian times and with a submarine origin of the >70-m.y.-long Jurassic hiatus.

Estimation of the normal boiling point of organic compounds via group contributions

The normal boiling point is a fundamental thermo-physical property, which is important in describing the transition between the vapor and liquid phases. Reliable method which can predict it is of great importance, especially for compounds where there are no experimental data available. In this work, an improved group contribution method, which is second order method, for determination of the normal boiling point of organic compounds based on the Joback functional first order groups with some changes and added some other functional groups was developed by using experimental data for 632 organic components. It could distinguish most of structural isomerism and stereoisomerism, which including the structural, cis- and trans- isomers of organic compounds. First and second order contributions for hydrocarbons and hydrocarbon derivatives containing carbon, hydrogen, oxygen, nitrogen, sulfur, fluorine, chlorine and bromine atoms, are given. The fminsearch mathematical approach from MATLAB software is used in this study to select an optimal collection of functional groups (65 functional groups) and subsequently to develop the model. This is a direct search method that uses the simplex search method of Lagarias et al. The results of the new method are compared to the several currently used methods and are shown to be far more accurate and reliable. The average absolute deviation of normal boiling point predictions for 632 organic compounds is 4.4350 K; and the average absolute relative deviation is 1.1047 %, which is of adequate accuracy for many practical applications.

RNase E is required for the maturation of ssrA RNA and normal ssrA RNA peptide-tagging activity

During recent studies of ribonucleolytic “degradosome” complexes of Escherichia coli, we found that degradosomes contain certain RNAs as well as RNase E and other protein components. One of these RNAs is ssrA (for small stable RNA) RNA (also known as tm RNA or 10Sa RNA), which functions as both a tRNA and mRNA to tag the C-terminal ends of truncated proteins with a short peptide and target them for degradation. Here, we show that mature 363-nt ssrA RNA is generated by RNase E cleavage at the CCA-3′ terminus of a 457-nt ssrA RNA precursor and that interference with this cleavage in vivo leads to accumulation of the precursor and blockage of SsrA-mediated proteolysis. These results demonstrate that RNase E is required to produce mature ssrA RNA and for normal ssrA RNA peptide-tagging activity. Our findings indicate that RNase E, an enzyme already known to have a central role in RNA processing and decay in E. coli, also has the previously unsuspected ability to affect protein degradation through its role in maturation of the 3′ end of ssrA RNA.

Similarities in normal and binocularly rivalrous viewing

We report here a series of observations—most of which the reader can experience directly—showing that distinct components of patterned visual stimuli (orthogonal lines of a different hue) vary in perception as sets. Although less frequent and often less complete, these perceptual fluctuations in normal viewing are otherwise similar to the binocular rivalry experienced when incompatible scenes are presented dichoptically.

Two Components of Actin-based Retrograde Flow in Sea Urchin Coelomocytes

Sea urchin coelomocytes represent an excellent experimental model system for studying retrograde flow. Their extreme flatness allows for excellent microscopic visualization. Their discoid shape provides a radially symmetric geometry, which simplifies analysis of the flow pattern. Finally, the nonmotile nature of the cells allows for the retrograde flow to be analyzed in the absence of cell translocation. In this study we have begun an analysis of the retrograde flow mechanism by characterizing its kinetic and structural properties. The supramolecular organization of actin and myosin II was investigated using light and electron microscopic methods. Light microscopic immunolocalization was performed with anti-actin and anti-sea urchin egg myosin II antibodies, whereas transmission electron microscopy was performed on platinum replicas of critical point-dried and rotary-shadowed cytoskeletons. Coelomocytes contain a dense cortical actin network, which feeds into an extensive array of radial bundles in the interior. These actin bundles terminate in a perinuclear region, which contains a ring of myosin II bipolar minifilaments. Retrograde flow was arrested either by interfering with actin polymerization or by inhibiting myosin II function, but the pathway by which the flow was blocked was different for the two kinds of inhibitory treatments. Inhibition of actin polymerization with cytochalasin D caused the actin cytoskeleton to separate from the cell margin and undergo a finite retrograde retraction. In contrast, inhibition of myosin II function either with the wide-spectrum protein kinase inhibitor staurosporine or the myosin light chain kinase–specific inhibitor KT5926 stopped flow in the cell center, whereas normal retrograde flow continued at the cell periphery. These differential results suggest that the mechanism of retrograde flow has two, spatially segregated components. We propose a “push–pull” mechanism in which actin polymerization drives flow at the cell periphery, whereas myosin II provides the tension on the actin cytoskeleton necessary for flow in the cell interior.

Vitronectin is not essential for normal mammalian development and fertility.

Vitronectin (VN) is an abundant glycoprotein present in plasma and the extracellular matrix of most tissues. Though the precise function of VN in vivo is unknown, it has been implicated as a participant in diverse biological processes, including cell attachment and spreading, complement activation, and regulation of hemostasis. The major site of synthesis appears to be the liver, though VN is also found in the brain at an early stage of mouse organogenesis, suggesting that it may play an important role in mouse development. Genetic deficiency of VN has not been reported in humans or in other higher organisms. To examine the biologic function of VN within the context of the intact animal, we have established a murine model for VN deficiency through targeted disruption of the murine VN gene. Southern blot analysis of DNA obtained from homozygous null mice demonstrates deletion of all VN coding sequences, and immunological analysis confirms the complete absence of VN protein expression in plasma. However, heterozygous mice carrying one normal and one null VN allele and homozygous null mice completely deficient in VN demonstrate normal development, fertility, and survival. Sera obtained from VN-deficient mice are completely deficient in "serum spreading factor" and plasminogen activator inhibitor 1 binding activities. These observations demonstrate that VN is not essential for cell adhesion and migration during normal mouse development and suggest that its role in these processes may partially overlap with other adhesive matrix components.

Correlation of the Corneal Toricity Between Anterior and Posterior Corneal Surfaces in the Normal Human Eye

Purpose: To evaluate the correlation of the magnitude of corneal toricity and power vector components of both corneal surfaces measured with a Scheimpflug photography-based system. Methods: A total of 117 healthy normal eyes of 117 subjects selected randomly with ages ranging from 7 to 80 years were included. All eyes received an anterior segment and corneal analysis with the Sirius system (CSO) evaluating the anterior and posterior mean toricity for 3 and 7 mm (aAST and pAST). The vector components J0 and J45 as well as the overall strength blur (B) were calculated for each keratometric measurement using the procedure defined by Thibos and Horner. Results: The coefficient of correlation between aAST and pAST was 0.52 and 0.62 and the mean anteroposterior ratio for toricity was 0.46 ± 0.39 and 0.57 ± 0.75 for 3 and 7 mm, respectively. These ratios correlated significantly with aAST, anterior corneal J0, and manifest refraction J0 (r ≥ 0.39, P < 0.01). The coefficient of correlation was 0.69 and 0.81 between anterior and posterior J0 for 3 and 7 mm, respectively. For J45, the coefficients were 0.62 and 0.71, respectively. The linear regression analysis revealed that the pAST and power vectors could be predicted from the anterior corneal data (R2 ≥ 0.40, P < 0.01). Conclusions: The toricity and astigmatic power vector components of the posterior corneal surface in the human healthy eye are related to those of the anterior and therefore can be predicted consistently from the anterior toricity and astigmatic power vectors.

A Mixture model with random-effects components for clustering correlated gene-expression profiles

Motivation: The clustering of gene profiles across some experimental conditions of interest contributes significantly to the elucidation of unknown gene function, the validation of gene discoveries and the interpretation of biological processes. However, this clustering problem is not straightforward as the profiles of the genes are not all independently distributed and the expression levels may have been obtained from an experimental design involving replicated arrays. Ignoring the dependence between the gene profiles and the structure of the replicated data can result in important sources of variability in the experiments being overlooked in the analysis, with the consequent possibility of misleading inferences being made. We propose a random-effects model that provides a unified approach to the clustering of genes with correlated expression levels measured in a wide variety of experimental situations. Our model is an extension of the normal mixture model to account for the correlations between the gene profiles and to enable covariate information to be incorporated into the clustering process. Hence the model is applicable to longitudinal studies with or without replication, for example, time-course experiments by using time as a covariate, and to cross-sectional experiments by using categorical covariates to represent the different experimental classes. Results: We show that our random-effects model can be fitted by maximum likelihood via the EM algorithm for which the E(expectation) and M(maximization) steps can be implemented in closed form. Hence our model can be fitted deterministically without the need for time-consuming Monte Carlo approximations. The effectiveness of our model-based procedure for the clustering of correlated gene profiles is demonstrated on three real datasets, representing typical microarray experimental designs, covering time-course, repeated-measurement and cross-sectional data. In these examples, relevant clusters of the genes are obtained, which are supported by existing gene-function annotation. A synthetic dataset is considered too.

Using urea dilution to standardise cellular and non-cellular components of pleural and bronchoalveolar lavage (BAL) fluids in the cat

A technique to standardise the analysis of cellular and non-cellular components in epithelial lining fluid (ELF) collected during saline lavage of pulmonary and pleural cavities was developed using the urea dilution method. Bronchoalveolar lavage (BAL) and pleural lavage (PL) fluids were collected from 12 clinically healthy cats. Total and differential cell counts in BAL fluid were within normal ranges for the cat, while cell Counts in PL fluid were assumed to be normal based on clinical health during examination, auscultation and lactate dehydrogenase (LDH) activities being comparable with other species. The major clinical implication of this study was that nucleated cell counts within feline ELF could not be predicted from analysis of lavage fluid which suggests that calculation of the proportion of ELF in lavage fluid by the urea dilution method may be necessary to avoid misdiagnosis of health or disease in pulmonary or pleural cavities. (C) 2005 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Simultaneous grouping in cochlear implant listeners:can abrupt changes in level be used to segregate components from a complex tone?

A sudden increase in the amplitude of a component often causes its segregation from a complex tone, and shorter rise times enhance this effect. We explored whether this also occurs in implant listeners (n?=?8). Condition 1 used a 3.5-s “complex tone” comprising concurrent stimulation on five electrodes distributed across the array of the Nucleus CI24 implant. For each listener, the baseline stimulus level on each electrode was set at 50% of the dynamic range (DR). Two 1-s increments of 12.5%, 25%, or 50% DR were introduced in succession on adjacent electrodes within the “inner” three of those activated. Both increments had rise and fall times of 30 and 970 ms or vice versa. Listeners reported which increment was higher in pitch. Some listeners performed above chance for all increment sizes, but only for 50% increments did all listeners perform above chance. No significant effect of rise time was found. Condition 2 replaced amplitude increments with decrements. Only three listeners performed above chance even for 50% decrements. One exceptional listener performed well for 50% decrements with fall and rise times of 970 and 30 ms but around chance for fall and rise times of 30 and 970 ms, indicating successful discrimination based on a sudden rise back to baseline stimulation. Overall, the results suggest that implant listeners can use amplitude changes against a constant background to pick out components from a complex, but generally these must be large compared with those required in normal hearing. For increments, performance depended mainly on above-baseline stimulation of the target electrodes, not rise time. With one exception, performance for decrements was typically very poor.

Phase equilibrium studies at normal pressures

A total pressure apparatus has been developed to measure vapour-liquid equilibrium data on binary mixtures at atmospheric and sub-atmospheric pressures. The method gives isothermal data which can be obtained rapidly. Only measurements of total pressure are made as a direct function of composition of synthetic liquid phase composition, the vapour phase composition being deduced through the Gibbs-Duhem relationship. The need to analyse either of the phases is eliminated. As such the errors introduced by sampling and analysis are removed. The essential requirements are that the pure components be degassed completely since any deficiency in degassing would introduce errors into the measured pressures. A similarly essential requirement was that the central apparatus would have to be absolutely leak-tight as any leakage of air either in or out of the apparatus would introduce erroneous pressure readings. The apparatus was commissioned by measuring the saturated vapour pressures of both degassed water and ethanol as a function of temperature. The pressure-temperature data on degassed water measured were directly compared with data in the literature, with good agreement. Similarly the pressure-temperature data were measured for ethanol, methanol and cyclohexane and where possible a direct comparison made with the literature data. Good agreement between the pure component data of this work and those available in the literature demonstrates firstly that a satisfactory degassing procedure has been achieved and that secondly the measurements of pressure-temperature are consistent for any one component; since this is true for a number of components, the measurements of both temperature and pressure are both self-consistent and of sufficient accuracy, with an observed compatibility between the precision/accuracy of the separate means of measuring pressure and temperature. The liquid mixtures studied were of ethanol-water, methanol-water and ethanol-cyclohexane. The total pressure was measured as the composition inside the equilibrium cell was varied at a set temperature. This gave P-T-x data sets for each mixture at a range of temperatures. A standard fitting-package from the literature was used to reduce the raw data to yield y-values to complete the x-y-P-T data sets. A consistency test could not be applied to the P-T-x data set as no y-values were obtained during the experimental measurements. In general satisfactory agreement was found between the data of this work and those available in the literature. For some runs discrepancies were observed, and further work recommended to eliminate the problems identified.

Separate influences of acoustic AM and FM sensitivity on the phonological decoding skills of impaired and normal readers

Developmental dyslexia is associated with deficits in the processing of basic auditory stimuli. Yet it is unclear how these sensory impairments might contribute to poor reading skills. This study better characterizes the relationship between phonological decoding skills, the lack of which is generally accepted to comprise the core deficit in reading disabilities, and auditory sensitivity to amplitude modulation (AM) and frequency modulation (FM). Thirty-eight adult subjects, 17 of whom had a history of developmental dyslexia, completed a battery, of psychophysical measures of sensitivity to FM and AM at different modulation rates, along with a measure of pseudoword reading accuracy and standardized assessments of literacy and cognitive skills. The subjects with a history of dyslexia were significantly less sensitive than controls to 2-Hz FM and 20-Hz AM only. The absence of a significant group difference for 2-Hz AM shows that the dyslexics do not have a general deficit in detecting all slow modulations. Thresholds for detecting 2-Hz and 240-Hz FM and 20-Hz AM correlated significantly with pseudoword reading accuracy. After accounting for various cognitive skills, however, multiple regression analyses showed that detection thresholds for both 2-Hz FM and 20-Hz AM were significant and independent predictors of pseudoword reading ability in the entire sample. Thresholds for 2-Hz AM and 240-Hz FM did not explain significant additional variance in pseudoword reading skill, it is therefore possible that certain components of auditory processing of modulations are related to phonological decoding skills, whereas others are not.

InP-based active and passive components for communication systems at 2 μm

Progress on advanced active and passive photonic components that are required for high-speed optical communications over hollow-core photonic bandgap fiber at wavelengths around 2 μm is described in this paper. Single-frequency lasers capable of operating at 10 Gb/s and covering a wide spectral range are realized. A comparison is made between waveguide and surface normal photodiodes with the latter showing good sensitivity up to 15 Gb/s. Passive waveguides, 90° optical hybrids, and arrayed waveguide grating with 100-GHz channel spacing are demonstrated on a large spot-size waveguide platform. Finally, a strong electro-optic effect using the quantum confined Stark effect in strain-balanced multiple quantum wells is demonstrated and used in a Mach-Zehnder modulator capable of operating at 10 Gb/s.

Prevalence of the metabolic syndrome and its components in Brazilian women with polycystic ovary syndrome

SOARES, Elvira Maria Mafaldo et al. Prevalence of the metabolic syndrome and its components in Brazilian women with polycystic ovary syndrome. Fertility and Sterility, v.89, n.3, p.649-655, mar. 2008