Weight reduction improves biochemistry and histology in patients with chronic hepatitis C

Hepatitis C virus (HCV) is a major cause of chronic liver disease that may progress to cirrhosis. Antiviral treatment is successful in less than 50% of patients, is costly and causes debilitating side effects. For these reasons, additional therapies to limit the progression of liver disease are urgently required. Steatosis is found in 60% of patients with HCV and is strongly associated with more severe fibrosis. Improvements in biochemical parameters may be seen with weight reduction, however the effects on liver histology have not been investigated. We propose that in patients with chronic HCV and steatosis, obesity contributes to fat in the liver, which results in increased fibrosis and progression to cirrhosis. This study investigated the effect of weight reduction on liver biochemistry and histology in patients with HCV and the success of weight maintenance after an intensive intervention. We examined the effect of a 12 week diet and exercise program where all subjects were seen weekly by the Dietician, with the goal of achieving a 0.5 kg weight loss per week. Biochemistry was monitored monthly and a liver biopsy was performed prior to and 3-6 months after the intervention period. Patients then entered a 12 month weight maintenance program with monthly dietetic review. After 12 weeks there was a mean weight loss of 5.9 ± 3.2 kg and a mean reduction in waist circumference of 9.0 ± 5.0 cm. In 16 of the 19 patients, serum ALT levels fell progressively with weight loss. Mean fasting insulin fell from 16 to 11 mmol/L (p

Weight reduction in patients with chronic HCV reduces circulating insulin levels

Steatosis occurs in >50% of patients with chronic HCV. In patients with viral genotype 3, steatosis may be a cytopathic effect of the virus. However in many patients with HCV, the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease (NAFLD) ie related to increased body mass index (BMI). We studied the effect of a 12 week weight reduction program on metabolic parameters in subjects with chronic HCV genotype 1 (Group 1, n = 16), genotype 3 (Group 2, n = 13) and patients with NAFLD (Group 3, n = 13). A liver biopsy was performed prior to and 3-6 months after the intervention period in 15 patients. The mean (SD) BMI of subjects in groups 1, 2 and 3 was 30.7 (4.0), 29.0 (5.2) and 33.3 (7.7), respectively. There was no significant difference in the amount of weight loss, change in waist circumference, change in ALT or reduction in steatosis between the 3 groups. Mean (SD) weight loss was 5.1 (3.7) kg. In those patients who lost weight, serum insulin (mean (SD) mU/L) changed from 17.8 (7.8) to 11.5 (4.8) (p = 0.003), 12.4 (5.0) to 8.4 (4.3) (p = 0.02), and 16.9 (7.3) to 17.8 (8.1) (p = 0.76) in Groups 1, 2 and 3, respectively. A small amount of weight loss is associated with a reduction in circulating insulin levels in patients with chronic HCV, particularly in genotype 1. In patients with NAFLD, the lack of a significant decrease in circulating insulin with weight reduction may reflect the higher initial BMI or may be due to the pathogenesis of this disorder.

(Review) Body mass index and risk of diabetes mellitus in the Asia-Pacific region

Few prospective data from the Asia Pacific region are available relating body mass index to the risk of diabetes. Our objective was to provide reliable age, sex and region specific estimates of the associations between body mass index and diabetes. Twenty-seven cohort studies from Asia, New Zealand and Australia, including 154,989 participants, contributed 1,244,793 person-years of follow-up. Outcome data included a combination of incidence of diabetes (based on blood glucose measurements) and fatal diabetes events. Hazard ratios were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk and smoking. During follow-up (mean = 8 years), 75 fatal diabetes events and 242 new cases of diabetes were documented. There were continuous positive associations between baseline body mass index and risk of diabetes with each 2 kg/m(2) lower body mass index associated with a 27% (23-30%) lower risk of diabetes. The associations were stronger in younger age groups, and regional comparisons demonstrated slightly stronger associations in Asian than in Australasian cohorts (P = 0.04). This overview provides evidence of a strong continuous association between body mass index and diabetes in the Asia Pacific region. The results indicate considerable potential for reduction in incidence of diabetes with population-wide lowering of body mass index in this region.

Analysis of dynamic process models for structural insight and model reduction .1. Structural identification measures

An important consideration in the development of mathematical models for dynamic simulation, is the identification of the appropriate mathematical structure. By building models with an efficient structure which is devoid of redundancy, it is possible to create simple, accurate and functional models. This leads not only to efficient simulation, but to a deeper understanding of the important dynamic relationships within the process. In this paper, a method is proposed for systematic model development for startup and shutdown simulation which is based on the identification of the essential process structure. The key tool in this analysis is the method of nonlinear perturbations for structural identification and model reduction. Starting from a detailed mathematical process description both singular and regular structural perturbations are detected. These techniques are then used to give insight into the system structure and where appropriate to eliminate superfluous model equations or reduce them to other forms. This process retains the ability to interpret the reduced order model in terms of the physico-chemical phenomena. Using this model reduction technique it is possible to attribute observable dynamics to particular unit operations within the process. This relationship then highlights the unit operations which must be accurately modelled in order to develop a robust plant model. The technique generates detailed insight into the dynamic structure of the models providing a basis for system re-design and dynamic analysis. The technique is illustrated on the modelling for an evaporator startup. Copyright (C) 1996 Elsevier Science Ltd

Analysis of dynamic models for structural insight and model reduction .2. A multi-stage compressor shutdown case-study

In this second paper, the three structural measures which have been developed are used in the modelling of a three stage centrifugal synthesis gas compressor. The goal of this case study is to determine the essential mathematical structure which must be incorporated into the compressor model to accurately model the shutdown of this system. A simple, accurate and functional model of the system is created via three structural measures. It was found that the model can be correctly reduced into its basic modes and that the order of the differential system can be reduced from 51(st) to 20(th). Of the 31 differential equational 21 reduce to algebraic relations, 8 become constants and 2 can be deleted thereby increasing the algebraic set from 70 to 91 equations. An interpretation is also obtained as to which physical phenomena are dominating the dynamics of the compressor add whether the compressor will enter surge during the shutdown. Comparisons of the reduced model performance against the full model are given, showing the accuracy and applicability of the approach. Copyright (C) 1996 Elsevier Science Ltd

Molecular motion in miscible polymer blends .1. Motion in blends of PEO and PVPh studied by solid-state C-13 T-1 rho measurements

Changes in molecular motion in blends of PEO-PVPh have been studied using measurements of C-13 T-1 rho relaxation times. C-13 T-1 rho relaxation has been confirmed as arising from spin-lattice interactions by observation of the variation in T-1 rho with rf field strength and temperature. In the pure homopolymers a minimum in T-1 rho is observed at ca. 50 K above the glass transition temperatures detected by DSC. After blending, the temperature of the minimum in T-1 rho for PEO increased, while that for PVPh decreased, however, the minima, which correspond to the temperatures where the average correlation times for reorientation are close to 3.1 mu s, are separated by 45 K (in a 45% PEO-PVPh blend). These phenomena are explained in terms of the local nature of T-1 rho measurements. The motions of the individual homopolymer chains are only partially coupled in the blend. A short T-1 rho has been observed for protonated aromatic carbons, and assigned to phenyl rings undergoing large-angle oscillatory motion, The effects of blending, and temperature, on the proportion of rings undergoing oscillatory motion are analyzed.

Measurements of neutral atom diffusion and electron-ion recombination by laser enhanced ionisation and planar laser induced fluorescence in an air-acetylene flame

The spatial and temporal evolution of a depleted atomic distribution created by laser enhanced ionisation (LEI) was employed to determine both a diffusion coefficient for sodium (Na) and an electron (e(-)) and sodium ion recombination rate coefficient in an analytical air-C2H2 flame. A depleted distribution of neutral sodium atoms was produced in a flame by ionising approximately 80% of the irradiated sodium atoms in a well defined region using a two step LEI excitation scheme. Following depletion by ionisation, planar laser induced fluorescence (PLIF) images of the depleted region recorded the diffusion and decay of the depleted Na distribution for different depletion-probe delays. From measurements of the diffused width of the distribution, an accurate diffusion coefficient D = (1.19 +/- 0.03) x 10(-3) m(2) s(-1) for Na was determined in teh burnt gases of the flame. Measurements of the integrated fluorescence intensity in the depleted region for different depletion-probe delays were related to an increase in atomic sodium concentration caused by electron-ion recombination. At high concentrations (greater than or equal to 50 mu g ml(-1)), where the electron and ion concentrations in the depleted region were assumed equal, a recombination rate coefficient of 4.2 x 10(-9) cm(3) s(-1) was calculated. (C) 1997 Elsevier Science B.V.

Optimal quantum measurements for phase-shift estimation in optical interferometry

Quantum information theory, applied to optical interferometry, yields a 1/n scaling of phase uncertainty Delta phi independent of the applied phase shift phi, where n is the number of photons in the interferometer. This 1/n scaling is achieved provided that the output state is subjected to an optimal phase measurement. We establish this scaling law for both passive (linear) and active (nonlinear) interferometers and identify the coefficient of proportionality. Whereas a highly nonclassical state is required to achieve optimal scaling for passive interferometry, a classical input state yields a 1/n scaling of phase uncertainty for active interferometry.

A mathematical model for Escherichia coli debris size reduction during high pressure homogenisation based on grinding theory

Experimental data for E. coli debris size reduction during high-pressure homogenisation at 55 MPa are presented. A mathematical model based on grinding theory is developed to describe the data. The model is based on first-order breakage and compensation conditions. It does not require any assumption of a specified distribution for debris size and can be used given information on the initial size distribution of whole cells and the disruption efficiency during homogenisation. The number of homogeniser passes is incorporated into the model and used to describe the size reduction of non-induced stationary and induced E. coil cells during homogenisation. Regressing the results to the model equations gave an excellent fit to experimental data ( > 98.7% of variance explained for both fermentations), confirming the model's potential for predicting size reduction during high-pressure homogenisation. This study provides a means to optimise both homogenisation and disc-stack centrifugation conditions for recombinant product recovery. (C) 1997 Elsevier Science Ltd.

Optimal quantum trajectories for discrete measurements

Using the method of quantum trajectories we show that a known pure state can be optimally monitored through time when subject to a sequence of discrete measurements. By modifying the way that we extract information from the measurement apparatus we can minimize the average algorithmic information of the measurement record, without changing the unconditional evolution of the measured system. We define an optimal measurement scheme as one which has the lowest average algorithmic information allowed. We also show how it is possible to extract information about system operator averages from the measurement records and their probabilities. The optimal measurement scheme, in the limit of weak coupling, determines the statistics of the variance of the measured variable directly. We discuss the relevance of such measurements for recent experiments in quantum optics.