A Concordance Method For Analyzing Categorical Time Series. An Application For The Search of Periodicities

A simple method for searching for periods in biological series is proposed. Because it is based on an auto-comparison of the observations within a series we call it the concordance method. It requires few theoritical assumptions. In fact, even the ever present stationarity condition is not used. The method is compared with competing methods based on the khi-square periodogram. It is shown that the concordance method is much better for analyzing multimodal and noisy series. Rhythms presenting simultaneously circadian and ultradian components can also be analyzed with this method.     

Phylogeny Derived from Coding Retroviral Genome Organization

When divergence between viral species is large, the analysis and comparison of nucleotide or protein sequences are dependent on mutation biases and multiple substitutions per site leading, among other things, to the underestimation of branch lengths in phylogenetic trees. To avoid the problem of multiply substituted sites, a method not directly based on the nucleic or protein sequences has been applied to retroviruses. It consisted of asking questions about genome structure or organization, and gene function, the series of answers creating coded sequences analyzed by phylogenic software. This method recovered the principal retroviral groups such as the lentiviruses and spumaviruses and highlighted questions and answers characteristic of each group of retroviruses. In general, there was reasonable concordance between the coded genome methodology and that based on conventional phylogeny of the integrase protein sequence, indicating that integrase was fixing mutations slowly enough to marginalize the problem of multiple substitutions at sites. To a first approximation, this suggests that the acquisition of novel genetic features generally parallels the fixation of amino acid substitutions. Received: 18 May 2001 / Accepted: 7 September 2001     

A statistical model for interpreting the antibiogram

Up to now, to interpret antibiotic susceptibility tests, the common practice has been to use: first, breakpoints without any quantitative justification, secondly, concordance curves between the different measurement techniques; these are not well adapted to the heterogeneous character of bacterial populations. We hereby propose another method: it is based on a global data analysis for each bacterial species, each antibiotic family and each measurement technique. So, we have drawn up a new model for the interpretation, both global and data-processed; it is based on qualifying classes, which are obtained and interpreted by hierarchical ascendent classification, principal components analysis, and comparison with pharmacological data. It can be used by any biologist. What is more, justified breakpoints with a numerical risk and quality control are defined. There are also some additional uses: evaluation of the effect of new antibiotics, standardization of new measurement techniques, detection of the emergence of new bacterial resistance in patients, guidance for research into unknown resistance mechanisms and characters.     

Clinical significance on MicroScan Rapid plus series using various antibiotic-resistant bacteria

MicroScan Rapid plus Neg II Series and MicroScan Rapid plus Pos Series by Siemens Healthcare Diagnostics K.K. are the panels which enable to measure identification and antimicrobial susceptibility testing quickly and we have confirmed that it is useful for detecting drug resistance bacteria. As the identification result of comparing Rapid plus series with the current panel by using 143 strains of various drug resistance bacteria, Gram positive cocci was 87. 7%, glucose fermenter was 100% and glucose non-fermenter was 77.3 in Gram negative bacilli. On the evaluation of antimicrobial susceptibility testing, Rapid plus series, in comparison with the current panel, confirmed the lower tendency of MIC value on some drugs, but it basically presented the good concordance rate. In terms of the reporting time of antimicrobial agent, non-fermenter or MRCNS reported the result as needed after 8 hours and it took a little longer time for the report of antimicrobial agent. On the other hand, 80% or higher of antimicrobial agent on panel was reported for intestinal bacteria in 4.5 hours and for MRSA in 6.5 hours. It enabled to report the testing result on the same day. Due to the results above, Rapid plus series was highly valued on the usability, such as the early detection of drug resistance bacteria and the selection of therapeutic agents.     

Fractal dimension and histogram method: Algorithm and some preliminary results of noise-like time series analysis

In the present work a methodological background for the histogram method of time series analysis is developed. Connection between shapes of smoothed histograms constructed on the basis of short segments of time series of fluctuations and the fractal dimension of the segments is studied. It is shown that the fractal dimension possesses all main properties of the histogram method. Based on it a further development of fractal dimension determination algorithm is proposed. This algorithm allows more precision determination of the fractal dimension by using the “all possible combination” method. The application of the method to noise-like time series analysis leads to results, which could be obtained earlier only by means of the histogram method based on human expert comparisons of histograms shapes.     

Sensor fusion by neural networks using spatially represented information

 A neural network model based on a lateral-inhibition-type feedback layer is analyzed with regard to its capabilities to fuse signals from two different sensors reporting the same event (“multisensory convergence”). The model consists of two processing stages. The input stage holds spatial representations of the sensor signals and transmits them to the second stage where they are fused. If the input signals differ, the model exhibits two different processing modes: with small differences it produces a weighted average of the input signals, whereas with large differences it enters a decision mode where one of the two signals is suppressed. The dynamics of the network can be described by a series of two first-order low-pass filters, whose bandwidth depends nonlinearly on the level of concordance of the input signals. The network reduces sensor noise by means of both its averaging and filtering properties. Hence noise suppression, too, depends on the level of concordance of the inputs. When the network's neurons have internal noise, sensor noise suppression is reduced but still effective as long as the input signals do not differ strongly. The possibility of extending the scheme to three and more inputs is discussed. Received: 2 August 2000 / Accepted in revised form: 3 May 2001     

Quantitative trait associated microarray gene expression data analysis

Selection on phenotypes may cause genetic change. To understand the relationship between phenotype and gene expression from an evolutionary viewpoint, it is important to study the concordance between gene expression and profiles of phenotypes. In this study, we use a novel method of clustering to identify genes whose expression profiles are related to a quantitative phenotype. Cluster analysis of gene expression data aims at classifying genes into several different groups based on the similarity of their expression profiles across multiple conditions. The hope is that genes that are classified into the same clusters may share underlying regulatory elements or may be a part of the same metabolic pathways. Current methods for examining the association between phenotype and gene expression are limited to linear association measured by the correlation between individual gene expression values and phenotype. Genes may be associated with the phenotype in a nonlinear fashion. In addition, groups of genes that share a particular pattern in their relationship to phenotype may be of evolutionary interest. In this study, we develop a method to group genes based on orthogonal polynomials under a multivariate Gaussian mixture model. The effect of each expressed gene on the phenotype is partitioned into a cluster mean and a random deviation from the mean. Genes can also be clustered based on a time series. Parameters are estimated using the expectation-maximization algorithm and implemented in SAS. The method is verified with simulated data and demonstrated with experimental data from 2 studies, one clusters with respect to severity of disease in Alzheimer's patients and another clusters data for a rat fracture healing study over time. We find significant evidence of nonlinear associations in both studies and successfully describe these patterns with our method. We give detailed instructions and provide a working program that allows others to directly implement this method in their own analyses.     

Modeling concordance correlation via GEE to evaluate reproducibility

Clinical studies are often concerned with assessing whether different raters/methods produce similar values for measuring a quantitative variable. Use of the concordance correlation coefficient as a measure of reproducibility has gained popularity in practice since its introduction by Lin (1989, Biometrics 45, 255-268). Lin's method is applicable for studies evaluating two raters/two methods without replications. Chinchilli et al. (1996, Biometrics 52, 341-353) extended Lin's approach to repeated measures designs by using a weighted concordance correlation coefficient. However, the existing methods cannot easily accommodate covariate adjustment, especially when one needs to model agreement. In this article, we propose a generalized estimating equations (GEE) approach to model the concordance correlation coefficient via three sets of estimating equations. The proposed approach is flexible in that (1) it can accommodate more than two correlated readings and test for the equality of dependent concordant correlation estimates; (2) it can incorporate covariates predictive of the marginal distribution; (3) it can be used to identify covariates predictive of concordance correlation; and (4) it requires minimal distribution assumptions. A simulation study is conducted to evaluate the asymptotic properties of the proposed approach. The method is illustrated with data from two biomedical studies.     

Energy-Based Wavelet De-Noising of Hydrologic Time Series

De-noising is a substantial issue in hydrologic time series analysis, but it is a difficult task due to the defect of methods. In this paper an energy-based wavelet de-noising method was proposed. It is to remove noise by comparing energy distribution of series with the background energy distribution, which is established from Monte-Carlo test. Differing from wavelet threshold de-noising (WTD) method with the basis of wavelet coefficient thresholding, the proposed method is based on energy distribution of series. It can distinguish noise from deterministic components in series, and uncertainty of de-noising result can be quantitatively estimated using proper confidence interval, but WTD method cannot do this. Analysis of both synthetic and observed series verified the comparable power of the proposed method and WTD, but de-noising process by the former is more easily operable. The results also indicate the influences of three key factors (wavelet choice, decomposition level choice and noise content) on wavelet de-noising. Wavelet should be carefully chosen when using the proposed method. The suitable decomposition level for wavelet de-noising should correspond to series'' deterministic sub-signal which has the smallest temporal scale. If too much noise is included in a series, accurate de-noising result cannot be obtained by the proposed method or WTD, but the series would show pure random but not autocorrelation characters, so de-noising is no longer needed.     

Phenological description of natural vegetation in southern Africa using remotely‐sensed vegetation data

Abstract. Various attempts have been made to describe and map the vegetation of southern Africa with recent efforts having an increasingly ecologi cal context. Vegetation classification is usually based on vegetation physiognomy and floristic composition, but phenology is useful source of information which is rarely used, although it can contribute functional information on ecosystems. The objectives of this study were to identify a suite of variables derived from time‐series NDVI data that best describe the phenological phenomena of vegetation in southern Africa and, secondly, to assess a classification of pixels of the study area based on NDVI variables using a preexisting map of the biomes that was delimited on the basis of life forms and climate. A number of variables were derived from the satellite data for describing phenological phenomena, which were analysed by multivariate techniques to determine which variables best explained the variation in the satellite data. This set of variables was used to produce a phenological classification of the vegetation of southern Africa, the results of which are discussed in relation to their concordance with the existing biome boundaries.     

Detecting Small Amounts of Gene Flow from Phylogenies of Alleles

The method of coalescents is used to find the probability that none of the ancestors of alleles sampled from a population are immigrants. If that is the case for samples from two or more populations, then there would be concordance between the phylogenies of those alleles and the geographic locations from which they are drawn. This type of concordance has been found in several studies of mitochondrial DNA from natural populations. It is shown that if the number of sequences sampled from each population is reasonably large (10 or more), then this type of concordance suggests that the average number of individuals migrating between populations is likely to be relatively small (Nm less than 1) but the possibility of occasional migrants cannot be excluded. The method is applied to the data of E. Bermingham and J. C. Avise on mtDNA from the bowfin, Amia calva.     

Use of an enzymeimmunoassay (EIA) for quantitation of cytosolic and nuclear estrogen receptor, and correlation with progesterone receptor in human breast cancer

We have adapted a commercially available enzyme immunoassay for ER (ER-EIA) for use with nuclear extracts of breast carcinoma specimens, and have examined the data obtained in relation to the results from cytosolic ER-EIA and radioligand (DCC) assays and from DCC assays for PgR. In a series of 139 carcinoma specimens, we observed a very significant correlation between the cytosolic ER concentration as measured by the EIA and DCC methods, and also between the log10 of the concentration of ER in the cytosolic and nuclear fractions assayed by the ER-EIA method. The correlation between nuclear ER and cytosolic PgR was also highly significant, but not as close as for cytosolic ER. If 130 fmol ER/mg DNA was used as a "cut-off" point to discriminate between specimens "positive" and "negative" for ERN, there was 87% concordance in receptor status between ERN and cytosolic ER, and 79% concordance between ERN and cytosolic PgR. Forty-one percent of specimens were positive or borderline for both ERN and cytosolic PgR, and it is suggested that this receptor combination may be a valuable predictive factor in prognosis and response to hormonal treatment.     

Convergent/Divergent Synthesis of a Linker‐Varied Series of Dyes for Dye‐Sensitized Solar Cells Based on the D35 Donor

A series of four new dyes, based on the D35 type donor moiety with varied linker units, is synthesized using a facile convergent/divergent method, enabled by an improved synthesis of the D35 donor. The dyes are evaluated in dye sensitized solar cells with Co(II/III)(bpy)₃‐based electrolytes. By extending the linker fragment, higher photocurrents and solar energy conversion efficiencies are achieved. It is also found that the linker unit plays a crucial role in maintaining a high open‐circuit photovoltage. Based on the photovoltaic performance it is concluded that the hexylthiophene unit is the most suitable for this purpose, as it allows further enhancement of the already high open‐circuit voltage of D35 to 0.92 V. The best dye in this series reaches an efficiency of 6.8%.     

系统理论指导下辩证思维模式与抗休克决策

休克是由于有效循环血量不足引发的微循环障碍而表现一系列症候群,作为一种系统性疾病,病因十分复杂多样,诊疗过程中的临床决策应全面而富有针对性,并充分考虑到救治措施的协调一致和互相配合。系统论主张整体大于部分之和强调的就是措施之间的整体化效果,充分考虑到患者个体间差异,辩证分析不同类型休克、不同个体间不同表现,在系统理论指导下的富有针对性措施间协调一致的决策模式才是较为完整的休克救治临床决策模式。     

A new method of sequential sampling to obtain the population estimates with a fixed level of precision

A simple method of sequential sampling is developed which would make it automatically possible to secure, without excess sampling, a predetermined level of precision for a series of population estimates being required. It appears to have wide application to sampling field populations under various situations since it is simply based upon the relationship of variance to mean for which a comprehensive formula deduced for biological populations from the linearity in the regression of mean crowding on mean density could be adopted. Some problems that may arise in practical application of the method are also discussed.     

Linear selection indices for non-linear profit functions

Summary Two methods of deriving linear selection indices for non-linear profit functions have been proposed. One is by linear approximation of profit, and another is the graphical method of Moav and Hill (1966). When profit is defined as the function of population means, the graphical method is optimal. In this paper, profit is defined as the function of the phenotypic values of individual animals; it is then shown that the graphical method is not generally optimal. We propose new methods for constructing selection indices. First, a numerical method equivalent to the graphical method is proposed. Furthermore, we propose two other methods using quadratic approximation of profit: one is based on Taylor series about means before selection, and the other is based on Tayler series about means after selection. Among these different methods, it is shown that the method using quadratic approximation based on Taylor series about means after selection is the most efficient.     

A method for detecting the coding DNA for a protein of known sequence in a collection of chimeric plasmids constructed with cDNAs.

A rapid screening method for recognising plasmids containing copies of cDNA corresponding to proteins of known amino acid sequences, is described. The method is based on the computer prediction of the possible restriction sites in the cloned DNAs. It was tested on a series of proteins with known coding DNA sequences and a series of plasmid cloned cDNAs made from pure chicken globin mRNA.     

Bismarck Brown As A Stain For Mucoproteins

Bismarck brown has been used for many years as a stain for mucin. But some types of mucoprotein are so water-labile that they cannot be demonstrated by the aqueous or weak alcoholic solutions usually employed. It has been found that Bismarck brown in slightly acidified, strong alcoholic, solution stains mucin. A simple method is given for using this solution for staining water-stable mucoproteins. Another method is included in which full precautions are given for avoidance of water at all stages subsequent to fixation. This method must be used for the more water-labile mucoproteins. By the use of these methods, it has been possible to demonstrate a wide range of mucoproteins including those of the mast cells of Hardie and that of the zona pellucida of the graafian follicle.     

Comparison of Four Immunochemical Methods For the Measurement of Oestrogen Receptor Levels In Breast Cancer

Four methods of assessing oestrogen receptor (ER) status were compared in 33 patients with operable primary breast cancer. The methods used to assess the ER status were immunocytochemical assay (ER-ICA) of frozen sections, fine needle aspirates and imprint material and enzyme immunoassay (ER-EIA) of tumour tissue. A mean overall ER positivity of 45% (15 out of 33), 41% (13 out of 32) and 21% (six out of 29) was obtained by immunocytochemical (ER-ICA) staining of frozen sections, fine needle aspirates and tumour imprints, respectively, and a mean overall ER positivity of 42% (14 out of 33) was obtained by ER-EIA. The concordance of ER positivity in pairs of data obtained from different method combinations was found to range between 72 and 91%. However, statistically there was no significant difference between the four methods on the basis of the data obtained. Good comparability has been shown between the three tissue analyses and therefore the method of choice is technically not immediately apparent.     

A mixture model approach to the tests of concordance and discordance between two large-scale experiments with two-sample groups

MOTIVATION: Due to advances in experimental technologies, such as microarray, mass spectrometry and nuclear magnetic resonance, it is feasible to obtain large-scale data sets, in which measurements for a large number of features can be simultaneously collected. However, the sample sizes of these data sets are usually small due to their relatively high costs, which leads to the issue of concordance among different data sets collected for the same study: features should have consistent behavior in different data sets. There is a lack of rigorous statistical methods for evaluating this concordance or discordance. METHODS: Based on a three-component normal-mixture model, we propose two likelihood ratio tests for evaluating the concordance and discordance between two large-scale data sets with two sample groups. The parameter estimation is achieved through the expectation-maximization (E-M) algorithm. A normal-distribution-quantile-based method is used for data transformation. RESULTS: To evaluate the proposed tests, we conducted some simulation studies, which suggested their satisfactory performances. As applications, the proposed tests were applied to three SELDI-MS data sets with replicates. One data set has replicates from different platforms and the other two have replicates from the same platform. We found that data generated by SELDI-MS showed satisfactory concordance between replicates from the same platform but unsatisfactory concordance between replicates from different platforms. AVAILABILITY: The R codes are freely available at http://home.gwu.edu/~ylai/research/Concordance.