Robust test method for time-course microarray experiments.

BACKGROUND: In a time-course microarray experiment, the expression level for each gene is observed across a number of time-points in order to characterize the temporal trajectories of the gene-expression profiles. For many of these experiments, the scientific aim is the identification of genes for which the trajectories depend on an experimental or phenotypic factor. There is an extensive recent body of literature on statistical methodology for addressing this analytical problem. Most of the existing methods are based on estimating the time-course trajectories using parametric or non-parametric mean regression methods. The sensitivity of these regression methods to outliers, an issue that is well documented in the statistical literature, should be of concern when analyzing microarray data. RESULTS: In this paper, we propose a robust testing method for identifying genes whose expression time profiles depend on a factor. Furthermore, we propose a multiple testing procedure to adjust for multiplicity. CONCLUSIONS: Through an extensive simulation study, we will illustrate the performance of our method. Finally, we will report the results from applying our method to a case study and discussing potential extensions.

Local models for exploratory analysis of hydrological extremes

Trend analysis is widely used for detecting changes in hydrological data. Parametric methods for this employ pre-specified models and associated tests to assess significance, whereas non-parametric methods generally apply rank tests to the data. Neither approach is suitable for exploratory analysis, because parametric models impose a particular, perhaps unsuitable, form of trend, while testing may confirm that trend is present but does not describe its form. This paper describes semi-parametric approaches to trend analysis using local likelihood fitting of annual maximum and partial duration series and illustrates their application to the exploratory analysis of changes in extremes in sea level and river flow data. Bootstrap methods are used to quantify the variability of estimates.

In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads

In recent years, the use of swelling polymeric matrices for the encapsulation and controlled release of protein drugs has received significant attention. The purpose of the present study was to investigate the release of albumin, a model protein from alginate/hydroxypropyl-methylcellulose (HPMC) gel beads. A hydrogel system comprised of two natural, hydrophilic polymers; sodium alginate and HPMC was studied as a carrier of bovine serum albumin (BSA) which was used as a model protein. The morphology, bead size and the swelling ratio were studied in different physical states; fully swollen, dried and reswollen using scanning electron microscopy and image analysis. Finally the effect of different alginate/HPMC ratios on the BSA release profile in physiological saline solution was investigated. Swelling experiments revealed that the bead diameter increases with the viscosity of the alginate solution while the addition of HPMC resulted in a significant increase of the swelling ratio. The BSA release patterns showed that the addition of HPMC increased the protein-release rate while the release mechanism fitted the Peppas model. Alginate/HPMC beads prepared using the ionic gelation exhibited high BSA loading efficiency for all formulations. The presence of HPMC increased the swelling ability of the alginate beads while the particle size remained unaffected. Incorporation of HPMC in the alginate gels also resulted in improved BSA release in physiological saline solution. All formulations presented a non-Fickian release mechanism described by the Peppas model. In addition, the implementation of non-parametric tests showed significant differences in the release patterns between the alginate/HPMC and the pure alginate beads, respectively.

Seasonal plankton dynamics along a cross-shelf gradient off northern Spain

The development of population models able to reproduce the dynamics of zooplankton is a central issue when trying to understand how a changing environment would affect zooplankton in the future. Using 10 years of monthly data on phytoplankton and zooplankton abundance in the Bay of Biscay from the IEO's RADIALES time-series programme, we built non-parametric Generalized Additive Models (GAMs) able to reproduce the dynamics of plankton on the basis of environmental factors (nutrients, temperature, upwelling and photoperiod). We found that the interaction between these two plankton components is approximately linear, whereas the effects of environmental factors are non-linear. With the inclusion of the environmental variability, the main seasonal and inter-annual dynamic patterns observed within the studied plankton assemblage indicate the prevalence of bottom-up regulatory control. The statistically deduced models were used to simulate the dynamics of the phytoplankton and zooplankton. A good agreement between observations and simulations was obtained, especially for zooplankton. We are presently developing spatio-temporal GAM models for the North Sea based on the Continuous Plankton Recorder database.

Variaciones termométricas en la planta del pie y piernas valorada en corredores antes y después de correr 30 km

La termometría es una técnica no invasiva que permite cuantificar los cambios en la temperatura cutánea y evaluarla de forma cuantitativa. El aumento significativo de la temperatura puede indicar la existencia de patología. Se ha demostrado que la actividad muscular induce procesos de transferencia de calor entre los músculos y las capas superficiales de tejido. En este estudio queremos cuantificar los cambios de temperatura que se producen en los músculos del pie y miembro inferior tras una carrera de 30 km, para ello hemos utilizado una cámara termográfica de alta resolución. Contamos con la colaboración voluntaria de 32 sujetos sanos a los que procedimos a tomar fotografías de la planta del pie, parte anterior de la pierna, parte posterior de la pierna, parte anterior del muslo y parte posterior del muslo en dos etapas, primero antes de la carrera y segunda toma después de la carrera de 30 km, de esta manera pudimos valorar si había o no variación de temperatura en las zonas seleccionadas. Tras el análisis de los datos obtenidos encontramos significativas variaciones térmicas en Talón, cabeza primer metatarsiano, cabeza segundo metatarsiano, cabeza tercer metatarsiano, cabeza cuarto metatarsiano, cabeza quinto metatarsiano, apófisis estiloides quinto metatarsiano, arco longitudinal interno, maléolo interno, maléolo externo, peroneo lateral largo, vasto interno, vasto externo, recto femoral, tensor de la fascia lata, inserción cuádriceps, gemelo interno, tendón de Aquiles y Biceps femoral.

Fracture Mechanics Analysis of the Dentine-Luting Cement Interface.

The objectives of this study were to determine the fracture toughness of adhesive interfaces between dentine and clinically relevant, thin layers of dental luting cements. Cements tested included a conventional glass-ionomer, F (Fuji I), a resin-modified glass-ionomer, FP (Fuji Plus) and a compomer cement, D (DyractCem). Ten miniature short-bar chevron notch specimens were manufactured for each cement, each comprising a 40 µm thick chevron of lute, between two 1.5 mm thick blocks of bovine dentine, encased in resin composite. The interfacial KIC results (MN/m3/2) were median (range): F; 0.152 (0.14-0.16), FP; 0.306 (0.27-0.37), D; 0.351 (0.31-0.37). Non-parametric statistical analysis showed that the fracture toughness of F was significantly lower (p

Real time monitoring of the polymerisation of PMMA bone cement using Raman spectroscopy

In this investigation Raman spectroscopy was shown to be a method that could be used to monitor the polymerisation of PMMA bone cement. Presently there is no objective method that orthopaedic surgeons can use to quantify the curing process of cement during surgery. Raman spectroscopy is a non-invasive, non-destructive technique that could offer such an option. Two commercially available bone cements (Palacos® R and SmartSet® HV) and different storage conditions (4 and 22°C) were used to validate the technique. Raman spectroscopy was found to be repeatable across all conditions with the completion of the polymerisation process particularly easy to establish. All tests were benchmarked against current temperature monitoring methods outlined in ISO and ASTM standards. There was found to be close agreement with the standard methods and the Raman spectroscopy used in this study.

Significant correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy

Prior family and adoption studies have suggested a genetic relationship between schizophrenia and schizotypy. However, this has never been verified using linkage methods. We therefore attempted to test for a correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy. The Irish study of high-density schizophrenia families comprises 270 families with at least two members with schizophrenia or poor-outcome schizoaffective disorder (n = 637). Non-psychotic relatives were assessed using the structured interview for schizotypy (n = 746). A 10-cM multipoint, non-parametric, autosomal genomewide scan of schizophrenia was performed in Merlin. A scan of a quantitative trait comprising ratings of DSM-III-R criteria for schizotypal personality disorder in non-psychotic relatives was also performed. Schizotypy logarithm of the odds (LOD) scores were regressed onto schizophrenia LOD scores at all loci, with adjustment for spatial autocorrelation. To assess empirical significance, this was also carried out using 1000 null scans of schizotypy. The number of jointly linked loci in the real data was compared to distribution of jointly linked loci in the null scans. No markers were suggestively linked to schizotypy based on strict Lander Kruglyak criteria. Schizotypy LODs predicted schizophrenia LODs above chance expectation genome wide (empirical P = 0.04). Two and four loci yielded nonparametric LOD (NPLs) > 1.0 and > 0.75, respectively, for both schizophrenia and schizotypy (genome-wide empirical P = 0.04 and 0.02, respectively). These results suggest that at least a subset of schizophrenia susceptibility genes also affects schizotypy in non-psychotic relatives. Power may therefore be increased in molecular genetic studies of schizophrenia if they incorporate measures of schizotypy in non-psychotic relatives.

Is Human Development Multidimensional?

Stiglitz's Commission on the Measurement of Economic Performance and Social Progress (CMEPSP) argued that well-being is multidimensional and identified eight distinct dimensions. Conventional linear techniques confirm that a large number of dimensions are needed to describe development. In contrast, a new non-linear technique that we introduce from chaos theory shows that a smaller number of dimensions are needed to span the development space. From the analysis, variables representing the Health, Education, Inequality and Individual Rights areas of life quality would provide a broad picture of development, whereas income per capita adds little extra information.

Study of fibre distribution and orientations in UHPFRC by electrical resistivity and mechanical tests

This paper presents experimental tests carried out on steel fibre reinforced concrete samples, including mechanical tests as well as non-destructive technique (electrical resistivity) and non destructive technique on cores (X-ray). Electrical resistivity measurements are done as a blind test, to characterise the electrical anisotropy and deduce the distribution and the orientation of fibres. These results are compared to X-ray imaging to check the quality of the non destructive evaluation. Then, flexural and compressive strength are measured on specimens to assess the influence of fibre distribution on the concrete properties.

An efficient particle filter for color-based tracking in complex scenes

In this paper, we introduce an efficient method for particle selection in tracking objects in complex scenes. Firstly, we improve the proposal distribution function of the tracking algorithm, including current observation, reducing the cost of evaluating particles with a very low likelihood. In addition, we use a partitioned sampling approach to decompose the dynamic state in several stages. It enables to deal with high-dimensional states without an excessive computational cost. To represent the color distribution, the appearance of the tracked object is modelled by sampled pixels. Based on this representation, the probability of any observation is estimated using non-parametric techniques in color space. As a result, we obtain a Probability color Density Image (PDI) where each pixel points its membership to the target color model. In this way, the evaluation of all particles is accelerated by computing the likelihood p(z|x) using the Integral Image of the PDI.

Lateralisation of language function in young adults born very preterm

Objective: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm.

Subjects: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls.

Method: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance.

Results: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area.

Conclusions: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.

A new method for estimating liquidity risk: Insights from a liquidity-adjusted CAPM framework

This paper proposes a new non-parametric method for estimating model-free, time-varying liquidity betas which builds on realized covariance and volatility theory. Working under a liquidity-adjusted CAPM framework we provide evidence that liquidity risk is a factor priced in the Greek stock market, mainly arising from the covariation of individual liquidity with local market liquidity, however, the level of liquidity seems to be an irrelevant variable in asset pricing. Our findings provide support to the notion that liquidity shocks transmitted across securities can cause market-wide effects and can have important implications for portfolio diversification strategies. ©2012 Elsevier B.V. All rights reserved.

Fundus autofluorescence in the diagnosis of cystoid macular oedema

Aim: To determine the sensitivity and specificity of the non-invasive imaging technique, fundus autofluorescence (AF), in the diagnosis of cystoid macular oedema (CMO), using fluorescein angiography as the reference standard. Design: Retrospective, consecutive, observational case series. Methods: Ninety-six consecutive patients with CMO suspected clinically were selected from the AF database of the Retina Unit, Ophthalmology Department, Grampian University Hospitals-NHS Trust, between August 2004 and June 2006. Only patients in whom CMO was secondary to (1) cataract extraction, (2) inherited retinopathies, (3) inflammatory eye disease or (4) idiopathic cases were included in this study. Only patients in whom AF images had been performed within 2 weeks of FFA and, when obtained following FFA, there was a minimum gap of 4 days ("washing out" period), were considered eligible for this study. A total of 34 eyes from 34 patients were eligible and were included in this study. FFA was used as the reference test to confirm the presence of CMO, and, based on fluorescein angiography (FFA), CMO was graded as either mild or florid. AF images were examined in a masked fashion for the presence or absence of CMO. The sensitivity and specificity of AF in detecting CMO were then calculated. Results: CMO was seen on AF imaging as round or oval areas at the fovea with an AF signal similar to that of background levels. At this site (fovea), the AF signal is usually reduced compared with background, due to the blockage caused by luteal pigment. The diagnosis of CMO based on AF imaging had 81% sensitivity and 69% specificity when compared with the reference standard FFA. Based on the FFA, there were 12 cases of florid CMO and eight of mild CMO. Of the former, CMO was detected with AF imaging in 100% (12/12 eyes), and of the latter, in 50% (4/8 eyes). Conclusions: AF imaging can be used as a rapid, non-invasive technique in the diagnosis of CMO.

Nonparametric Estimation of Data Dimensionality Prior to Data Compression: the case of the Human Development Index

In many applications in applied statistics researchers reduce the complexity of a data set by combining a group of variables into a single measure using factor analysis or an index number. We argue that such compression loses information if the data actually has high dimensionality. We advocate the use of a non-parametric estimator, commonly used in physics (the Takens estimator), to estimate the correlation dimension of the data prior to compression. The advantage of this approach over traditional linear data compression approaches is that the data does not have to be linearized. Applying our ideas to the United Nations Human Development Index we find that the four variables that are used in its construction have dimension three and the index loses information.