Fault reconstruction in linear dynamic systems using multivariate statistics

Treasure et al. (2004) recently proposed a new sub space-monitoring technique, based on the N4SID algorithm, within the multivariate statistical process control framework. This dynamic-monitoring method requires considerably fewer variables to be analysed when compared with dynamic principal component analysis (PCA). The contribution charts and variable reconstruction, traditionally employed for static PCA, are analysed in a dynamic context. The contribution charts and variable reconstruction may be affected by the ratio of the number of retained components to the total number of analysed variables. Particular problems arise if this ratio is large and a new reconstruction chart is introduced to overcome these. The utility of such a dynamic contribution chart and variable reconstruction is shown in a simulation and by application to industrial data from a distillation unit.

Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy

Aims/hypothesis: Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design.

Methods: White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A ? 2 test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing.

Results: We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups.

Conclusions/interpretation: The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.

Health status of children with cerebral palsy living in Europe: a multi-centre study

Aim The aim of this report is to describe the health status of 8–12-year-old children with cerebral palsy (CP) of all severities in Europe using the Child Health Questionnaire (CHQ).

Method A total of 818 children with CP from nine centres in defined geographical areas participated. CP type, gross and fine motor function, additional impairments were classified and family data were obtained. The CHQ was used to measure the parent's perception of their child's physical (PHY) and psychosocial (PSY) health.

Results PHY scores were lower than the reference samples with a median of 46. The severity of gross motor function influenced the CHQ scores significantly in the PHY scale with the lowest scores for children with least gross motor function. There were significant differences between the CP types in PHY with the higher scores for children with unilateral spastic and the lowest scores for children with bilateral spastic and dyskinetic CP type. Fine motor function severity significantly affected both the PHY and PSY scales. The severity of intellectual impairment was significantly associated with CHQ scores in most dimensions with higher scores for higher IQ level in PHY and PSY. Children with seizures during the last year had a significantly lower health compared with children without seizures. The results of the multivariate regression analyses (forward stepwise regression) of CHQ scores on CP subtype, gross and fine motor function, cognitive function, additional impairments, seizures, parental education and employment revealed gross motor function, cognitive level and type of school attended were significant prognostic factors.

Conclusion This report is based on the largest sample to date of children with CP. Health status as measured using the CHQ was affected in all children and was highly variable. Gross motor function level correlates with health from the PHY well-being perspective but the PSY and emotional aspects do not appear to follow the same pattern.

Multivariate Statistical Analysis Applied to an IL6 Signal Transduction Model in Hepatocytes

This paper introduces the application of linear multivariate statistical techniques, including partial least squares (PLS), canonical correlation analysis (CCA) and reduced rank regression (RRR), into the area of Systems Biology. This new approach aims to extract the important proteins embedded in complex signal transduction pathway models.The analysis is performed on a model of intracellular signalling along the janus-associated kinases/signal transducers and transcription factors (JAK/STAT) and mitogen activated protein kinases (MAPK) signal transduction pathways in interleukin-6 (IL6) stimulated hepatocytes, which produce signal transducer and activator of transcription factor 3 (STAT3).A region of redundancy within the MAPK pathway that does not affect the STAT3 transcription was identified using CCA. This is the core finding of this analysis and cannot be obtained by inspecting the model by eye. In addition, RRR was found to isolate terms that do not significantly contribute to changes in protein concentrations, while the application of PLS does not provide such a detailed picture by virtue of its construction.This analysis has a similar objective to conventional model reduction techniques with the advantage of maintaining the meaning of the states prior to and after the reduction process. A significant model reduction is performed, with a marginal loss in accuracy, offering a more concise model while maintaining the main influencing factors on the STAT3 transcription.The findings offer a deeper understanding of the reaction terms involved, confirm the relevance of several proteins to the production of Acute Phase Proteins and complement existing findings regarding cross-talk between the two signalling pathways.

Solid-state analysis of low-melting 1,3-dialkylimidazolium hexafluorophosphate salts (ionic liquids) by combined x-ray crystallographic and computational analyses

The interactions of ions in the solid state for a series of representative 1,3-dialkylimidazolium hexafluorophosphate salts (either ionic liquids or closely related) have been examined by crystallographic analysis, combined with the theoretical estimation of crystal-packing densities and lattice-interaction energies. Efficient close-packing of the ions in the crystalline states is observed, but there was no compelling evidence for specific directional hydrogen-bonding to the hexafluorophosphate anions or the formation of interstitial voids. The close-packing efficiency is supported by the theoretical calculation of ion volumes, crystal lattice energies, and packing densities, which correlated well with experimental data. The crystal density of the salts can be predicted accurately from the summation of free ion volumes and lattice energies calculated. Of even more importance for future work, on these and related salts, the solid-state density of 1,3-dialkylimidazolium hexafluorophosphate salts can be predicted with reasonable accuracy purely on the basis of on ab initio free ion volumes, and this allows prediction of lattice energies without necessarily requiring the crystal structures.

Unite and conquer: univariate and multivariate approaches for finding differentially expressed gene sets

Motivation: Recently, many univariate and several multivariate approaches have been suggested for testing differential expression of gene sets between different phenotypes. However, despite a wealth of literature studying their performance on simulated and real biological data, still there is a need to quantify their relative performance when they are testing different null hypotheses.

Results: In this article, we compare the performance of univariate and multivariate tests on both simulated and biological data. In the simulation study we demonstrate that high correlations equally affect the power of both, univariate as well as multivariate tests. In addition, for most of them the power is similarly affected by the dimensionality of the gene set and by the percentage of genes in the set, for which expression is changing between two phenotypes. The application of different test statistics to biological data reveals that three statistics (sum of squared t-tests, Hotelling's T2, N-statistic), testing different null hypotheses, find some common but also some complementing differentially expressed gene sets under specific settings. This demonstrates that due to complementing null hypotheses each test projects on different aspects of the data and for the analysis of biological data it is beneficial to use all three tests simultaneously instead of focusing exclusively on just one.

Late Holocene climatic changes in Tierra del Fuego based on multiproxy analyses of peat deposits

A ca. 1400-yr record from a raised bog in Isla Grande, Tierra del Fuego, Argentina, registers climate fluctuations, including a Medieval Warm Period, although evidence for the 'Little Ice Age' is less clear. Changes in temperature and/or precipitation were inferred from plant macrofossils, pollen, fungal spores, testate amebae, and peat humification. The chronology was established using a C-14 wiggle-matching technique that provides improved age control for at least part of the record compared to other sites. These new data are presented and compared with other lines of evidence from the Southern and Northern Hemispheres. A period of low local water tables occurred in the bog between A.D. 960-1020, which may correspond to the Medieval Warm Period date range of A.D. 950-1045 generated from Northern Hemisphere tree-ring data. A period of cooler and/or wetter conditions was detected between ca. A.D. 1030 and I 100 and a later period of cooler/wetter conditions estimated at ca. cal A.D. 1800-1930, which may correspond to a cooling episode inferred from Law Dome, Antarctica. (C) 2004 University of Washington. All rights reserved.

Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: The Prospective Epidemiological Study of Myocardial Infarction (PRIME)

Objective: To investigate the effect of alcohol intake patterns on ischaemic heart disease in two countries with contrasting lifestyles, Northern Ireland and France.
Design: Cohort data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) were analysed. Weekly alcohol consumption, incidence of binge drinking (alcohol >50 g on at least one day a week), incidence of regular drinking (at least one day a week, and alcohol <50 g if on only one occasion), volume of alcohol intake, frequency of consumption, and types of beverage consumed were assessed once at inclusion. All coronary events that occurred during the 10 year follow-up were prospectively registered. The relation between baseline characteristics and incidence of hard coronary events and angina events was assessed by Cox's proportional hazards regression analysis.
Setting: One centre in Northern Ireland (Belfast) and three centres in France (Lille, Strasbourg, and Toulouse).
Participants: 9778 men aged 50-59 free of ischaemic heart disease at baseline, who were recruited between 1991 and 1994.
Main outcome measures: Incident myocardial infarction and coronary death ("hard" coronary events), and incident angina pectoris.
Results: A total of 2405 men from Belfast and 7373 men from the French centres were included in the analyses, 1456 (60.5%) and 6679 (90.6%) of whom reported drinking alcohol at least once a week, respectively. Among drinkers, 12% (173/1456) of men in Belfast drank alcohol every day compared with 75% (5008/6679) of men in France. Mean alcohol consumption was 22.1 g/day in Belfast and 32.8 g/day in France. Binge drinkers comprised 9.4% (227/2405) and 0.5% (33/7373) of the Belfast and France samples, respectively. A total of 683 (7.0%) of the 9778 participants experienced ischaemic heart disease events during the 10 year follow-up: 322 (3.3%) hard coronary events and 361 (3.7%) angina events. Annual incidence of hard coronary events per 1000 person years was 5.63 (95% confidence interval 4.69 to 6.69) in Belfast and 2.78 (95% CI 2.41 to 3.20) in France. After multivariate adjustment for classic cardiovascular risk factors and centre, the hazard ratio for hard coronary events compared with regular drinkers was 1.97 (95% CI 1.21 to 3.22) for binge drinkers, 2.03 (95% CI 1.41 to 2.94) for never drinkers, and 1.57 (95% CI 1.11 to 2.21) for former drinkers for the entire cohort. The hazard ratio for hard coronary events in Belfast compared with in France was 1.76 (95% CI 1.37 to 2.67) before adjustment, and 1.09 (95% CI 0.79 to 1.50) after adjustment for alcohol patterns and wine drinking. Only wine drinking was associated with a lower risk of hard coronary events, irrespective of the country.
Conclusions: Regular and moderate alcohol intake throughout the week, the typical pattern in middle aged men in France, is associated with a low risk of ischaemic heart disease, whereas the binge drinking pattern more prevalent in Belfast confers a higher risk.