Robust multivariable control of complex biological processes

This paper addresses advanced control of a biological nutrient removal (BNR) activated sludge process. Based on a previously validated distributed parameter model of the BNR activated sludge process, we present robust multivariable controller designs for the process, involving loop shaping of plant model, robust stability and performance analyses. Results from three design case studies showed that a multivariable controller with stability margins of 0.163, 0.492 and 1.062 measured by the normalised coprime factor, multiplicative and additive uncertainties respectively give the best results for meeting performance robustness specifications. The controller robustly stabilises effluent nutrients in the presence of uncertainties with the behaviour of phosphorus accumulating organisms as well as to effectively attenuate major disturbances introduced as step changes. This study also shows that, performance of the multivariable robust controller is superior to multi-loops SISO PI controllers for regulating the BNR activated sludge process in terms of robust stability and performance and controlling the process using inlet feed flowrate is infeasible. (C) 2003 Elsevier Ltd. All rights reserved.

Interactive effects of MC1R and OCA2 on melanoma risk phenotypes

The relationships between MC1R gene variants and red hair, skin reflectance, degree of freckling and nevus count were investigated in 2331 adolescent twins, their sibs and parents in 645 twin families. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. Of nine MC1R variant alleles assayed, four common alleles were strongly associated with red hair and fair skin (Asp84Glu, Arg151Cys, Arg160Trp and Asp294His), with a further three alleles having low penetrance (Val60Leu, Val92Met and Arg163Gln). These variants were separately combined for the purposes of this analysis and designated as strong 'R' (OR=63.3; 95% CI 31.9-139.6) and weak 'r ' (OR=5.1; 95% CI 2.5-11.3) red hair alleles. Red-haired individuals are predominantly seen in the R/R and R/r groups with 67.1 and 10.8%, respectively. To assess the interaction of the brown eye color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln), which were confirmed as modifying eye color. MC1R genotype effects on constitutive skin color, freckling and mole count were modified by eye color, but not genotype for these two OCA2 SNPs. This is probably due to the association of these OCA2 SNPs with brown/green not blue eye color. Amongst individuals with a R/R genotype (but not R/r), those who also had brown eyes had a mole count twice that of those with blue eyes. This suggests that other OCA2 polymorphisms influence mole count and remain to be described.

Depression in young adolescents: Investigations using 2 and 3 factor versions of the parental bonding instrument

Associations between parenting style and depressive symptomatology in a community sample of young adolescents (N = 2596) were investigated using self-report measures including the Parental Bonding Instrument and the Center for Epidemiologic Studies Depression Scale. Specifically, the 25-item 2-factor and 3-factor models by Parker et al. (1979), Kendler's (1996) 16-item 3-factor model, and Parker's (1983) quadrant model for the Parental Bonding Instrument were compared. Data analysis included analysis of variance and logistic regression. Reanalysis of Parker's original scale indicates that overprotection is composed of separate factors: intrusiveness (at the individual level) and restrictiveness (in the social context). All models reveal significant independent contributions from paternal care, maternal care, and maternal overprotection (2-factor) or intrusiveness (3-factor) to moderate and serious depressive symptomatology, controlling for sex and family living arrangement. Additive rather than multiplicative interactions between care and overprotection were found. Regardless of the level of parental care and affection, clinicians should note that maternal intrusiveness is strongly associated with adverse psychosocial health in young adolescents.

Statistical modeling and projections of lung cancer mortality in 4 industrialized countries

The purpose of this work was to model lung cancer mortality as a function of past exposure to tobacco and to forecast age-sex-specific lung cancer mortality rates. A 3-factor age-period-cohort (APC) model, in which the period variable is replaced by the product of average tar content and adult tobacco consumption per capita, was estimated for the US, UK, Canada and Australia by the maximum likelihood method. Age- and sex-specific tobacco consumption was estimated from historical data on smoking prevalence and total tobacco consumption. Lung cancer mortality was derived from vital registration records. Future tobacco consumption, tar content and the cohort parameter were projected by autoregressive moving average (ARIMA) estimation. The optimal exposure variable was found to be the product of average tar content and adult cigarette consumption per capita, lagged for 2530 years for both males and females in all 4 countries. The coefficient of the product of average tar content and tobacco consumption per capita differs by age and sex. In all models, there was a statistically significant difference in the coefficient of the period variable by sex. In all countries, male age-standardized lung cancer mortality rates peaked in the 1980s and declined thereafter. Female mortality rates are projected to peak in the first decade of this century. The multiplicative models of age, tobacco exposure and cohort fit the observed data between 1950 and 1999 reasonably well, and time-series models yield plausible past trends of relevant variables. Despite a significant reduction in tobacco consumption and average tar content of cigarettes sold over the past few decades, the effect on lung cancer mortality is affected by the time lag between exposure and established disease. As a result, the burden of lung cancer among females is only just reaching, or soon will reach, its peak but has been declining for I to 2 decades in men. Future sex differences in lung cancer mortality are likely to be greater in North America than Australia and the UK due to differences in exposure patterns between the sexes. (c) 2005 Wiley-Liss, Inc.

Effects of reflex stimulus intensity and stimulus onset asynchrony on prepulse inhibition and perceived intensity of the blink-eliciting stimulus

Prepulse inhibition of the blink reflex is widely applied to investigate information processing deficits in schizophrenia and other psychiatric patient groups. The present experiment investigated the hypothesis that prepulse inhibition reflects a transient process that protects preattentive processing of the prepulse. Participants were presented with pairs of blinkeliciting noises, some preceded by a prepulse at a variable stimulus onset asynchrony (SOA), and were asked to rate the intensity of the second noise relative to the first. Inhibition of blink amplitude was greater for a 110-dB (A) noise than for a 95-dB(A) noise with a 120-ms SOA, whereas there was no difference with a 30-ms SOA. The perceived intensity was also lower for the 110-dB(A) noise than for the 95-dB(A) noise with the 120-ms SOA, but not with the 30-ms SOA. The parallel results support a relationship between prepulse inhibition of response amplitude and perceived intensity. However, the prepulse did not reduce intensity ratings relative to control trials in some conditions, suggesting that prepulse inhibition is not always associated with an attenuation of the perceived impact of the blink-eliciting stimulus.

A comparison of different choices for the regularization parameter in inverse electrocardiography models

Calculating the potentials on the heart’s epicardial surface from the body surface potentials constitutes one form of inverse problems in electrocardiography (ECG). Since these problems are ill-posed, one approach is to use zero-order Tikhonov regularization, where the squared norms of both the residual and the solution are minimized, with a relative weight determined by the regularization parameter. In this paper, we used three different methods to choose the regularization parameter in the inverse solutions of ECG. The three methods include the L-curve, the generalized cross validation (GCV) and the discrepancy principle (DP). Among them, the GCV method has received less attention in solutions to ECG inverse problems than the other methods. Since the DP approach needs knowledge of norm of noises, we used a model function to estimate the noise. The performance of various methods was compared using a concentric sphere model and a real geometry heart-torso model with a distribution of current dipoles placed inside the heart model as the source. Gaussian measurement noises were added to the body surface potentials. The results show that the three methods all produce good inverse solutions with little noise; but, as the noise increases, the DP approach produces better results than the L-curve and GCV methods, particularly in the real geometry model. Both the GCV and L-curve methods perform well in low to medium noise situations.