Testing symmetry and homogeneity in the almost ideal demand system with co-integrated data using fully modified estimation and the bootstrap

Conventional seemingly unrelated estimation of the almost ideal demand system is shown to lead to small sample bias and distortions in the size of a Wald test for symmetry and homogeneity when the data are co-integrated. A fully modified estimator is developed in an attempt to remedy these problems. It is shown that this estimator reduces the small sample bias but fails to eliminate the size distortion.. Bootstrapping is shown to be ineffective as a method of removing small sample bias in both the conventional and fully modified estimators. Bootstrapping is effective, however, as a method of removing. size distortion and performs equally well in this respect with both estimators.

Opportunities for reduction in acute toxicity testing via improved design

The conventional method for assessing acute oral toxicity (OECD Test Guideline 401) was designed to identify the median lethal dose (LD50), using the death of animals as an endpoint. Introduced as an alternative method (OECD Test Guideline 420), the Fixed Dose Procedure (FDP) relies on the observation of clear signs of toxicity, uses fewer animals and causes less suffering. More recently, the Acute Toxic Class method and the Up-and-Down Procedure have also been adopted as OECD test guidelines. Both of these methods also use fewer animals than the conventional method, although they still use death as an endpoint. Each of the three new methods incorporates a sequential dosing procedure, which results in increased efficiency. In 1999, with a view to replacing OECD Test Guideline 401, the OECD requested that the three new test guidelines be updated. This was to bring them in line with the regulatory needs of all OECD Member Countries, provide further reductions in the number of animals used, and introduce refinements to reduce the pain and distress experienced by the animals. This paper describes a statistical modelling approach for the evaluation of acute oral toxicity tests, by using the revised FDP for illustration. Opportunities for further design improvements are discussed.

Sequentially testing for a gene-drug interaction in a genomewide analysis

Assaying a large number of genetic markers from patients in clinical trials is now possible in order to tailor drugs with respect to efficacy. The statistical methodology for analysing such massive data sets is challenging. The most popular type of statistical analysis is to use a univariate test for each genetic marker, once all the data from a clinical study have been collected. This paper presents a sequential method for conducting an omnibus test for detecting gene-drug interactions across the genome, thus allowing informed decisions at the earliest opportunity and overcoming the multiple testing problems from conducting many univariate tests. We first propose an omnibus test for a fixed sample size. This test is based on combining F-statistics that test for an interaction between treatment and the individual single nucleotide polymorphism (SNP). As SNPs tend to be correlated, we use permutations to calculate a global p-value. We extend our omnibus test to the sequential case. In order to control the type I error rate, we propose a sequential method that uses permutations to obtain the stopping boundaries. The results of a simulation study show that the sequential permutation method is more powerful than alternative sequential methods that control the type I error rate, such as the inverse-normal method. The proposed method is flexible as we do not need to assume a mode of inheritance and can also adjust for confounding factors. An application to real clinical data illustrates that the method is computationally feasible for a large number of SNPs. Copyright (c) 2007 John Wiley & Sons, Ltd.

A comparison of two time-domain analysis procedures in the determination of VO2 kinetics by pseudorandom binary sequence exercise testing

The purpose of this study was to apply and compare two time-domain analysis procedures in the determination of oxygen uptake (VO2) kinetics in response to a pseudorandom binary sequence (PRBS) exercise test. PRBS exercise tests have typically been analysed in the frequency domain. However, the complex interpretation of frequency responses may have limited the application of this procedure in both sporting and clinical contexts, where a single time measurement would facilitate subject comparison. The relative potential of both a mean response time (MRT) and a peak cross-correlation time (PCCT) was investigated. This study was divided into two parts: a test-retest reliability study (part A), in which 10 healthy male subjects completed two identical PRBS exercise tests, and a comparison of the VO2 kinetics of 12 elite endurance runners (ER) and 12 elite sprinters (SR; part B). In part A, 95% limits of agreement were calculated for comparison between MRT and PCCT. The results of part A showed no significant difference between test and retest as assessed by MRT [mean (SD) 42.2 (4.2) s and 43.8 (6.9) s] or by PCCT [21.8 (3.7) s and 22.7 (4.5) s]. Measurement error (%) was lower for MRT in comparison with PCCT (16% and 25%, respectively). In part B of the study, the VO2 kinetics of ER were significantly faster than those of SR, as assessed by MRT [33.4 (3.4) s and 39.9 (7.1) s, respectively; P<0.01] and PCCT [20.9 (3.8) s and 24.8 (4.5) s; P < 0.05]. It is possible that either analysis procedure could provide a single test measurement Of VO2 kinetics; however, the greater reliability of the MRT data suggests that this method has more potential for development in the assessment Of VO2 kinetics by PRBS exercise testing.

Testing for significance of phase synchronisation dynamics in the EEG

A number of tests exist to check for statistical significance of phase synchronisation within the Electroencephalogram (EEG); however, the majority suffer from a lack of generality and applicability. They may also fail to account for temporal dynamics in the phase synchronisation, regarding synchronisation as a constant state instead of a dynamical process. Therefore, a novel test is developed for identifying the statistical significance of phase synchronisation based upon a combination of work characterising temporal dynamics of multivariate time-series and Markov modelling. We show how this method is better able to assess the significance of phase synchronisation than a range of commonly used significance tests. We also show how the method may be applied to identify and classify significantly different phase synchronisation dynamics in both univariate and multivariate datasets.

Evaluation of the use of high-density SNP genotyping to implement UPOV Model 2 for DUS testing in barley

Developments in high-throughput genotyping provide an opportunity to explore the application of marker technology in distinctness, uniformity and stability (DUS) testing of new varieties. We have used a large set of molecular markers to assess the feasibility of a UPOV Model 2 approach: “Calibration of threshold levels for molecular characteristics against the minimum distance in traditional characteristics”. We have examined 431 winter and spring barley varieties, with data from UK DUS trials comprising 28 characteristics, together with genotype data from 3072 SNP markers. Inter varietal distances were calculated and we found higher correlations between molecular and morphological distances than have been previously reported. When varieties were grouped by kinship, phenotypic and genotypic distances of these groups correlated well. We estimated the minimum marker numbers required and showed there was a ceiling after which the correlations do not improve. To investigate the possibility of breaking through this ceiling, we attempted genomic prediction of phenotypes from genotypes and higher correlations were achieved. We tested distinctness decisions made using either morphological or genotypic distances and found poor correspondence between each method.

Testing for unit roots in bounded time series

Many key economic and financial series are bounded either by construction or through policy controls. Conventional unit root tests are potentially unreliable in the presence of bounds, since they tend to over-reject the null hypothesis of a unit root, even asymptotically. So far, very little work has been undertaken to develop unit root tests which can be applied to bounded time series. In this paper we address this gap in the literature by proposing unit root tests which are valid in the presence of bounds. We present new augmented Dickey–Fuller type tests as well as new versions of the modified ‘M’ tests developed by Ng and Perron [Ng, S., Perron, P., 2001. LAG length selection and the construction of unit root tests with good size and power. Econometrica 69, 1519–1554] and demonstrate how these tests, combined with a simulation-based method to retrieve the relevant critical values, make it possible to control size asymptotically. A Monte Carlo study suggests that the proposed tests perform well in finite samples. Moreover, the tests outperform the Phillips–Perron type tests originally proposed in Cavaliere [Cavaliere, G., 2005. Limited time series with a unit root. Econometric Theory 21, 907–945]. An illustrative application to U.S. interest rate data is provided

Method for exploratory cluster analysis and visualisation of single-trial ERP ensembles

Background: The validity of ensemble averaging on event-related potential (ERP) data has been questioned, due to its assumption that the ERP is identical across trials. Thus, there is a need for preliminary testing for cluster structure in the data. New method: We propose a complete pipeline for the cluster analysis of ERP data. To increase the signalto-noise (SNR) ratio of the raw single-trials, we used a denoising method based on Empirical Mode Decomposition (EMD). Next, we used a bootstrap-based method to determine the number of clusters, through a measure called the Stability Index (SI). We then used a clustering algorithm based on a Genetic Algorithm (GA)to define initial cluster centroids for subsequent k-means clustering. Finally, we visualised the clustering results through a scheme based on Principal Component Analysis (PCA). Results: After validating the pipeline on simulated data, we tested it on data from two experiments – a P300 speller paradigm on a single subject and a language processing study on 25 subjects. Results revealed evidence for the existence of 6 clusters in one experimental condition from the language processing study. Further, a two-way chi-square test revealed an influence of subject on cluster membership.

Novel glycopolymer hydrogels as mucosa-mimetic materials to reduce animal testing

Glycopolymer hydrogels capable of mimicking mucosal tissue in mucoadhesion testing have been designed. Liquid formulations containing mucoadhesive polymers were found to be retained on these tissues to the same extent as ex vivo gastric mucosa, when using a dynamic method of assessing mucoadhesion.

Wheat seed embryo excision enables the creation of axenic seedlings and Koch’s postulates testing of putative bacterial endophytes

Early establishment of endophytes can play a role in pathogen suppression and improve seedling development. One route for establishment of endophytes in seedlings is transmission of bacteria from the parent plant to the seedling via the seed. In wheat seeds, it is not clear whether this transmission route exists, and the identities and location of bacteria within wheat seeds are unknown. We identified bacteria in the wheat (Triticum aestivum) cv. Hereward seed environment using embryo excision to determine the location of the bacterial load. Axenic wheat seedlings obtained with this method were subsequently used to screen a putative endophyte bacterial isolate library for endophytic competency. This absence of bacteria recovered from seeds indicated low bacterial abundance and/or the presence of inhibitors. Diversity of readily culturable bacteria in seeds was low with 8 genera identified, dominated by Erwinia and Paenibacillus. We propose that anatomical restrictions in wheat limit embryo associated vertical transmission, and that bacterial load is carried in the seed coat, crease tissue and endosperm. This finding facilitates the creation of axenic wheat plants to test competency of putative endophytes and also provides a platform for endophyte competition, plant growth, and gene expression studies without an indigenous bacterial background.

A device to improve the Schleger and Turner method for sweating rate measurements

The objective of this study was to test a device developed to improve the functionality, accuracy and precision of the original technique for sweating rate measurements proposed by Schleger and Turner [Schleger AV, Turner HG (1965) Aust J Agric Res 16:92-106]. A device was built for this purpose and tested against the original Schleger and Turner technique. Testing was performed by measuring sweating rates in an experiment involving six Mertolenga heifers subjected to four different thermal levels in a climatic chamber. The device exhibited no functional problems and the results obtained with its use were more consistent than with the Schleger and Turner technique. There was no difference in the reproducibility of the two techniques (same accuracy), but measurements performed with the new device had lower repeatability, corresponding to lower variability and, consequently, to higher precision. When utilizing this device, there is no need for physical contact between the operator and the animal to maintain the filter paper discs in position. This has important advantages: the animals stay quieter, and several animals can be evaluated simultaneously. This is a major advantage because it allows more measurements to be taken in a given period of time, increasing the precision of the observations and diminishing the error associated with temporal hiatus (e.g., the solar angle during field studies). The new device has higher functional versatility when taking measurements in large-scale studies (many animals) under field conditions. The results obtained in this study suggest that the technique using the device presented here could represent an advantageous alternative to the original technique described by Schleger and Turner.

Correlation Between Etest (R), Disk Diffusion, and Microdilution Methods for Antifungal Susceptibility Testing of Candida Species From Infection and Colonization

The correlation between the microdilution (MD), Etest (R) (ET), and disk diffusion (DD) methods was determined for amphotericin B, itraconazole and fluconazole. The minimal inhibitory concentration (MIC) of those antifungal agents was established for a total of 70 Candida spp. isolates from colonization and infection. The species distribution was: Candida albicans (n = 27), C. tropicalis (n = 17), C. glabrata (n = 16), C. parapsilosis (n = 8), and C. lusitaniae (n = 2). Non-Candida albicans Candida species showed higher MICs for the three antifungal agents when compared with C. albicans isolates. The overall concordance (based on the MIC value obtained within two dilutions) between the ET and the MD method was 83% for amphotericin B, 63% for itraconazole, and 64% for fluconazole. Considering the breakpoint, the agreement between the DD and MD methods was 71% for itraconazole and 67% for fluconazole. The DD zone diameters are highly reproducible and correlate well with the MD method, making agar-based methods a viable alternative to MD for susceptibility testing. However, data on agar-based tests for itraconazole and amphotericin B are yet scarce. Thus, further research must still be carded out to ensure the standardization to other antifungal agents. J. Clin. Lab. Anal. 23:324-330, 2009. (C) 2009 Wiley-Liss, Inc.

The direct determination of rare earth elements in basaltic and related rocks using ICP-MS: Testing the efficiency of microwave oven sample decomposition procedures

Tests are described showing the results obtained for the determination of REE and the trace elements Rb, Y, Zr, Nb, Cs, Ba, Hf, Ta, Pb, Th and U with ICP-MS methodology for nine basaltic reference materials, and thirteen basalts and amphibolites from the mafic-ultramafic Niquelandia Complex, central Brazil. Sample decomposition for the reference materials was performed by microwave oven digestion (HF and HNO(3), 100 mg of sample), and that for the Niquelandia samples also by Parr bomb treatment (5 days at 200 degrees C, 40 mg of sample). Results for the reference materials were similar to published values, thus showing that the microwave technique can be used with confidence for basaltic rocks. No fluoride precipitates were observed in the microwave-digested solutions. Total recovery of elements, including Zr and Hf, was obtained for the Niquelandia samples, with the exception of an amphibolite. For this latter sample, the Parr method achieved a total digestion, but not so the microwave decomposition; losses, however, were observed only for Zr and Hf, indicating difficulty in dissolving Zr-bearing minerals by microwave acid attack.

The Use of On-Line Computer adaptive Testing to raise Standardized Test Scores

Nursing school graduates are under pressure to pass the RN-NCLEX Exam on the first attempt since New York State monitors the results and uses them to evaluate the school’s nursing programs. Since the RN-NCLEX Exam is a standardized test, we sought a method to make our students better test takers. The use of on-line computer adaptive testing has raised our student’s standardized test scores at the end of the nursing course.

Testing Seasonal Unit Roots in Data at Any Frequency, an HEGY approach

This paper generalizes the HEGY-type test to detect seasonal unit roots in data at any frequency, based on the seasonal unit root tests in univariate time series by Hylleberg, Engle, Granger and Yoo (1990). We introduce the seasonal unit roots at first, and then derive the mechanism of the HEGY-type test for data with any frequency. Thereafter we provide the asymptotic distributions of our test statistics when different test regressions are employed. We find that the F-statistics for testing conjugation unit roots have the same asymptotic distributions. Then we compute the finite-sample and asymptotic critical values for daily and hourly data by a Monte Carlo method. The power and size properties of our test for hourly data is investigated, and we find that including lag augmentations in auxiliary regression without lag elimination have the smallest size distortion and tests with seasonal dummies included in auxiliary regression have more power than the tests without seasonal dummies. At last we apply the our test to hourly wind power production data in Sweden and shows there are no seasonal unit roots in the series.