Frontolimbic Response to Negative Feedback in Clinical Depression.

Functional neuroimaging suggests that limbic regions of the medial frontal cortex may be abnormally active in individuals with depression. These regions, including the anterior cingulate cortex, are engaged in both action regulation, such as monitoring errors and conflict, and affect regulation, such as responding to pain. The authors examined whether clinically depressed subjects would show abnormal sensitivity of frontolimbic networks as they evaluated negative feedback. Depressed subjects and matched control subjects performed a video game in the laboratory as a 256-channel EEG was recorded. Speed of performance on each trial was graded with a feedback signal of A, C, or F. By 350 ms after the feedback signal, depressed subjects showed a larger medial frontal negativity for all feedback compared with control subjects with a particularly striking response to the F grade. This response was strongest for moderately depressed subjects and was attenuated for subjects who were more severely depressed. Localization analyses suggested that negative feedback engaged sources in the anterior cingulate and insular cortices. These results suggest that moderate depression may sensitize limbic networks to respond strongly to aversive events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Results from the monitoring of pesticide residues in fruit and vegetables on the Danish market, 2000-01

To check compliance with the maximum residue levels in foods and to monitor the residue levels to enable an evaluation of the exposure of the Danish population to pesticides, a monitoring programme for pesticides residues in fruit and vegetables was performed. Sampling plans were designed based on previous findings and on consumption data. Samples (n = 4404) of mainly fresh conventionally and organically grown fruit and vegetables were collected at wholesalers and importers and at food processing companies. Of the samples, 3% were frozen products and 5% organically grown. Of the samples, 34% were of Danish origin, with 66% from other countries. Two accredited laboratories performed analyses of the samples using capillary gas chromatography, liquid chromatography and a spectrophotometric method. Reporting levels were set at the lowest calibration level or at the limit of determination. Residues were found in 60% of the samples of fruit but in only 18% of the vegetable samples. Residues above the maximum residue levels were found in 6% of all samples of fruit and in 2% of the vegetable samples.     

Safety evaluation of substances consumed as technical ingredients (food additives)

The different types of acceptable daily intakes (ADIs) are described as used by the FAO/WHO Expert Committee on Food Additives (JECFA) and the EEC Scientific Committee for Food (SCF). The allocation is discussed of a full ADI or a temporary ADI, and examples are given for the establishment (or withdrawal) of these ADIs. The flavours cinnamyl anthranillate and the solvent 2-nitropropane (both withdrawn), the sweeteners cyclamate and saccharin and the antioxidant BHA (all three changed) but not abolished. For BHA and saccharin the ADI was retained by both committees in spite of some evidence of carcinogenicity to experimental animals. ADI--'not specified' is specially discussed and it is recommended that numerical ADIs are used whenever possible. With an ADI--'not specified' it should be stated which use (and intake) levels are toxicologically acceptable. Some compounds evaluated by the two committees are discussed, e.g. the colours: Allura red AC, erythrosine, canthaxanthin and the caramels; three anti-oxidants: BHA, BHT and the gallates; the sweeteners: polyols, aspartame, saccharin and cyclamates. Four recommendations are made: (1) a numerical basis be given for the levels allocated an ADI--'not specified' or 'acceptable'; (2) lowering of the conventional safety factor be considered when the effects found are trivial--higher safety factors be considered when the toxic effects are serious or even irreversible; (3) ADIs should, whenever possible, be based on a combination of human and animal data; (4) ADIs might be allocated to compounds indicating animal carcinogenicity, if the compound is non-genotoxic, the mechanism clearly secondary and/or species-specific.     

Fast and one-step folding of closely and distantly related homologous proteins of a four-helix bundle family

Bovine acyl-coenzyme A binding protein is a four-helix bundle protein belonging to a group of homologous eukaryote proteins that binds medium and long-chain acyl-coenzyme A esters with a very high affinity. The three-dimensional structure of both the free and the ligated protein together with the folding kinetics have been described in detail for the bovine protein and with four new sequences reported here, a total of 16 closely related sequences ranging from yeasts and plants to human are known. The kinetics of folding and unfolding in different concentrations of guanidine hydrochloride together with equilibrium unfolding have been measured for bovine, rat and yeast acyl-coenzyme A binding protein. The bovine and rat sequences are closely related whereas the yeast is more distantly related to these. In addition to the three natural variants, kinetics of a bovine mutant protein, Tyr31 --> Asn, have been studied. Both the folding and unfolding rates in water of the yeast protein are 15 times faster than those of bovine. The folding rates in water of the two mammalian forms, rat and bovine, are similar, though still significantly different. A faster unfolding rate both for rat and the bovine mutant protein results from a lower stability of the native states of these. These hydrophobic regions, mini cores, have been identified in the three-dimensional structure of the bovine protein and found to be formed primarily by residues that have been conserved throughout the entire eukaryote evolution from yeasts to both plants and mammals as seen in the sample of 16 sequences. The conserved residues are found to stabilize helix-helix interactions and serve specific functional purposes for ligand binding. The fast one-step folding mechanism of ACBP has been shown to be a feature that seems to be maintained throughout evolution despite numerous differences in sequence and even dramatic differences in folding kinetics and protein stability. The protein study raises the question to what extent does the conserved hydrophobic residues provide a scaffold for an efficient one-step folding mechanism.     

A generalized autocovariance least-squares method for Kalman filter tuning

This paper discusses a method for estimating noise covariances from process data. In linear stochastic state-space representations the true noise covariances are generally unknown in practical applications. Using estimated covariances a Kalman filter can be tuned in order to increase the accuracy of the state estimates. There is a linear relationship between covariances and autocovariance. Therefore, the covariance estimation problem can be stated as a least-squares problem, which can be solved as a symmetric semidefinite least-squares problem. This problem is convex and can be solved efficiently by interior-point methods. A numerical algorithm for solving the symmetric is able to handle systems with mutually correlated process noise and measurement noise.     

Quality of life development during initial hemodialysis therapy and association with loss of residual renal function

Introduction: Health related quality of life (HRQOL) is markedly reduced in hemodialysis patients compared to the general population. We investigated the course of self‐reported HRQOL over time and the association with selected factors, focusing on changes in glomerular filtration rate (GFR). Methods: Eighty‐two newly started hemodialysis patients from the SAFIR cohort filled out the Kidney Disease Quality of Life Short Form Version 1.3 (KDQOL‐SF^TM) questionnaire at baseline, 6 and 12 months. The SAFIR study was a randomized, placebo‐controlled, double‐blind intervention study, examining the effects of the angiotensin II receptor blocker irbesartan. HRQOL was a secondary outcome measure. Main inclusion criteria: Dialysis vintage <1 year, left ventricular ejection fraction >30% and urinary output >300 mL/day. GFR was measured with mean creatinine and urea clearance from 24‐hour urine collections at baseline, 6 and 12 months. Findings: Irbesartan treatment did not affect HRQOL. Patients were pooled into one group for further analyses. Decline in GFR correlated significantly with decreasing HRQOL over time. HRQOL was stable over time, with a slight nonsignificant tendency toward improved HRQOL. The largest HRQOL‐differences (positive values equal improved HRQOL) observed during the 12 month study period were (mean[95% confidence interval]): Burden of kidney disease:6.4[?2.2;15.0], Role limitations‐physical:12.7[?2.1;27.5], and Role limitations‐emotional:9.7[?5.2;24.6]. Comorbidity, especially diabetes, hospital admissions, female gender, and age were strongly associated with lower HRQOL in cross sectional analysis. Discussion: Preservation of residual renal function seems to be important for HRQOL. In newly started HD patients, HRQOL showed little change after 12 months. HRQOL was negatively affected by comorbidity, especially diabetes, hospital admissions, female gender, and age.     

Comments on a commentary: statistical evaluation of split mouth caries trials

When results of split mouth caries trials are reported, the most frequently used outcome measures are "effectiveness" and "net gain". In a recent review by Riordan & FitzGerald (Community Dent Oral Epidemiol 1994;22:192-7) of the statistical analysis of data from such trials, the close connection between effectiveness and the traditional epidemiological outcome measure, relative risk, was pointed out and the latter measure was recommended. The confidence intervals for these parameters were, however, incorrect. This note provides valid confidence intervals for net gain, effectiveness and relative risk based on data from split mouth trials and presents examples of the calculations.     

Effect of micro-channel geometry on fluid flow and mixing

Understanding the flow fields at the micro-scale is key to developing methods of successfully mixing fluids for micro-scale applications. This paper investigates flow characteristics and mixing efficiency of three different geometries in micro-channels. The geometries of these channels were rectangular with a dimension of; 300 μm wide, 100 μm deep and 50 mm long. In first channel there was no obstacle and in the second channel there were rectangular blocks of dimension 300 μm long and 150 μm wide are placed in the flow fields with every 300 μm distance attaching along the channel wall. In the third geometry, there were 100 μm wide fins with 150° angle which were placed at a distance of 500 μm apart from each other attached with the wall along the 50 mm channel. Fluent software of Computational Fluid Dynamics (CFD) was used to investigate the flow characteristics within these microfluidic model for three different geometries. A species 2D model was created for three geometries and simulations were run in order to investigate the mixing behaviour of two different fluid with viscosity of water (1 mPa s). Models were only built to investigate the effect of geometry, therefore only one fluid with similar viscosity was used in these models. Velocity vector plots were used in the CFD analysis to visualise the fluid flow path. Mass fractions of fluid were used to analyse the mixing efficiency. Two different colours for water were used to simulate the effect of two different fluids. The results showed that the mixing behaviour strongly depended on the channel geometry when other parameters such as fluid inlet velocity, viscosity and pressure of fluids were kept constant. In two geometries lateral pressure and swirling vortexes were developed which provided better mixing results. Creation of swirling vortexes increased diffusion gradients which enhanced diffusive mixing.     

Improving convergence of Iterative Feedback Tuning

Iterative Feedback Tuning constitutes an attractive control loop tuning method for processes in the absence of an accurate process model. It is a purely data driven approach aiming at optimizing the closed loop performance. The standard formulation ensures an unbiased estimate of the loop performance cost function gradient with respect to the control parameters. This gradient is important in a search algorithm. The extension presented in this paper further ensures informative data to improve the convergence properties of the method and hence reduce the total number of required plant experiments especially when tuning for disturbance rejection. Informative data is achieved through application of an external probing signal in the tuning algorithm. The probing signal is designed based on a constrained optimization which utilizes an approximate black box model of the process. This model estimate is further used to guarantee nominal stability and to improve the parameter update using a line search algorithm for determining the iteration step size. The proposed algorithm is compared to the classical formulation in a simulation study of a disturbance rejection problem. This type of problem is notoriously difficult for Iterative Feedback Tuning due to the lack of excitation from the reference.