Polarisation mode dispersion correlations with the coarse-step method

Having a fixed differential-group delay (DGD) term b′ in the coarse-step method results in a repetitive pattern in the autocorrelation function (ACF). We solve this problem by inserting a varying DGD term at each integration step. Furthermore we compute the range of values needed for b′ and simulate the phenomenon of polarisation mode dispersion for different statistical distributions of b′. We examine systematically the modified coarse-step method compared to the analytical model, through our simulation results. © 2006 Elsevier B.V. All rights reserved.

Rules for mapping a conceptual model onto various data base management systems. Available in 2 volumes.

The design and implementation of data bases involve, firstly, the formulation of a conceptual data model by systematic analysis of the structure and information requirements of the organisation for which the system is being designed; secondly, the logical mapping of this conceptual model onto the data structure of the target data base management system (DBMS); and thirdly, the physical mapping of this structured model into storage structures of the target DBMS. The accuracy of both the logical and physical mapping determine the performance of the resulting systems. This thesis describes research which develops software tools to facilitate the implementation of data bases. A conceptual model describing the information structure of a hospital is derived using the Entity-Relationship (E-R) approach and this model forms the basis for mapping onto the logical model. Rules are derived for automatically mapping the conceptual model onto relational and CODASYL types of data structures. Further algorithms are developed for partly automating the implementation of these models onto INGRES, MIMER and VAX-11 DBMS.

Interaction of quinolone antibiotics with the human intestinal CACO-2 cell model

The transport of a group of quinolone antibiotics across the human intestinal model, Caco-2 cells, was investigated. It was found that the transport of the quinolones generally correlated with the lipophilicity of the compounds, indicating the passive diffusional transcellular processes were involved. However, it was observed that the transport in both directions apical-to-basolateral and basolateral-to-apical was not equivalent, and polarised transport occurred. For all the quinolones studied except, BMS-284756-01, it was found that the basolateral-to-apical transport was significantly greater than the apical-to-basolateral transport. This finding suggested that the quinolones underwent a process of active secretion. The pKas and logPs for the quinolones were determined using potentiometric titrations. The measured logP values were compared with those determined using theoretical methods. The theoretical methods for calculating logP including the Moriguchi method correlated poorly with the measured logP values. Further investigations revealed that there may be an active transporter involved in the apical-to-basolateral transport of quinolones as well. This mechanism was sensitive to competing quinolones, but, it was unaffected by the metabolic inhibitor combination of sodium azide (15mM) with 2-deoxy-D-glucose (50mM). The basolateral-to-apical transport of quinolones was found to be sensitive to inhibition by a number of different inhibitors. The metabolic inhibitors, sodium azide (15mM) with 2-deoxy-D-glucose (50mM) and 2,4-dinitrophenol (1mM), were able to reduce the basolateral-to-apical transport of quinolones. A reduction in temperature from 37°C to 2°C caused an 80-fold decrease in the transport of gatifloxacin in both directions, however, this effect was not sufficient to abolish the greater basolateral-to-apical secretion. As with apical-to-basolateral transport, it was found that quinolones competed with gatifloxacin for basolateral-to-apical transport, both ofloxacin (100μM) and norfloxacin (100μM) significantly (P<0.003) decreased the basolateral-to-apical transport of gatifloxacin; however, ciprofloxacin (100μM and 300μM) had no effect. A number of inhibitors of various transport systems were also investigated. It was found that the anion transport inhibitor, probenecid (100 μM) had a significant inhibitory effect on the basolateral-to-apical transport of ciprofloxacin (P=0.039), while the cation transport inhibitor cimetidine (100μM and 500μM) had no effect. The organic anion exchange inhibitor 4,4'diisothiocyanostilbene-2-2' -disulphonic acid DIDS (400μM) also had a significant inhibitory effect (P=O.O 13). The PgP inhibitor and anion exchange inhibitor verapamil (400Mμ) was able to completely abolish the basolateral-to-apical secretion of gatifloxacin and bring it into line with the apical-to-basolateral flux. In conclusion, the apical-to-basolateral and basolateral-toapical transport of quinolones involved an active component. The basolateral-to-apical secretion was abolished by a verapamil (400μM), a bisubstrate for PgP and the anion transporter.

Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS • A population pharmacokinetic model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit. AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients. METHODS Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16–28.0 kg) who received intravenous potassium canrenoate (K-canrenoate) as part of their intensive care therapy for removal of retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analyzed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM. RESULTS A one compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (l h−1) = 11.4 × (WT/70.0)0.75 and V/F (l) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 l h−1 and 21.4 l, respectively, resulting in an elimination half-life of 11.2 h. CONCLUSIONS The range of estimated CL/F in the study population was 0.67–7.38 l h−1. The data suggest that adjustment of K-canrenoate dosage according to body weight is appropriate in paediatric patients.

Increases in renal ε-(γ-glutamyl)-lysine crosslinks result from compartment-specific changes in tissue transglutaminase in early experimental diabetic nephropathy:Pathologic implications

Diabetic nephropathy (DN) is characterized by an early, progressive expansion and sclerosis of the glomerular mesangium leading to glomerulosclerosis. This is associated with parallel fibrosis of the renal interstitium. In experimental renal scarring, the protein cross-linking enzyme, tissue transglutaminase (tTg), is up-regulated and externalized causing an increase in its crosslink product, e-(γ-glutamyl)-lysine, in the extracellular space. This potentially contributes to the extracellular matrix (ECM) accumulation central to tissue fibrosis by increasing deposition and inhibiting breakdown. We investigated if a similar mechanism may contribute to the ECM expansion characteristic of DN using the rat streptozotocin model over 120 days. Whole kidney e-(γ-glutamyl)-lysine (HPLC analysis) was significantly increased from Day 90 (+337%) and peaked at Day 120 (+650%) (p <0.05). Immunofluorescence showed this increase to be predominantly extracellular in the peritubular interstitial space, but also in individual glomeruli. Total kidney transglutaminase (Tg) was not elevated. However, using a Tg in situ activity assay, increased Tg was detected in both the extracellular interstitial space and glomeruli by Day 60, with a maximal 53% increase at Day 120 (p <0.05). Using a specific anti-tTg antibody, immunohistochemistry showed a similar increase in extracellular enzyme in the interstitium and glomeruli. To biochemically characterize glomerular changes, glomeruli were isolated by selective sieving. In line with whole kidney measurement, there was an increase in glomerular e-(γ-glutamyl) lysine (+ 361%); however, in the glomeruli this was associated with increases in Tg activity (+228%) and tTg antigen by Western blotting (+215%). Importantly, the ratio of glomerular e-(γ-glutamyl) lysine to hydroxyproline increased by 2.2-fold. In DN, changes in the kidney result in increased translocation of tTg to the extracellular environment where high Ca2+ and low GTP levels allow its activation. In the tubulointerstitium this is independent of increased tTg production, but dependent in the glomerulus. This leads to excessive ECM cross-linking, contributing to the renal fibrosis characteristic of progressive DN.

Representing spray zone with cross flow as a well-mixed compartment in a high shear granulator

The spray zone is an important region to control nucleation of granules in a high shear granulator. In this study, a spray zone with cross flow is quantified as a well-mixed compartment in a high shear granulator. Granulation kinetics is quantitatively derived at both particle-scale and spray zone-scale. Two spatial decay rates, DGSDR (droplet-granule spatial decay rate) ζDG and DPSDR (droplet-primary particle spatial decay rate) ζDP, which are functions of volume fraction and diameter of particulate species within the powder bed, are defined to simplify the deduction. It is concluded that in cross flow, explicit analytical results show that the droplet concentration is subject to exponential decay with depth which produces a numerically infinite depth of spray zone in a real penetration process. In a well-mixed spray zone, the depth of the spray zone is 4/(ζDG + ζDP) and π2/3(ζDG + ζDP) in cuboid and cylinder shape, respectively. The first-order droplet-based collision rates of, nucleation rate B0 and rewetting rate RW0 are uncorrelated with the flow pattern and shape of the spray zone. The second-order droplet-based collision rate, nucleated granule-granule collision rate RGG, is correlated with the mixing pattern. Finally, a real formulation case of a high shear granulation process is used to estimate the size of the spray zone. The results show that the spray zone is a thin layer at the powder bed surface. We present, for the first time, the spray zone as a well-mixed compartment. The granulation kinetics of a well-mixed spray zone could be integrated into a Population Balance Model (PBM), particularly to aid development of a distributed model for product quality prediction.

Quality of life and application of the transtheoretical model to diabetes self -management behaviors in older adults with type 2 diabetes

One in five adults 65 years and older has diabetes. Coping with diabetes is a lifelong task, and much of the responsibility for managing the disease falls upon the individual. Reports of non-adherence to recommended treatments are high. Understanding the additive impact of diabetes on quality of life issues is important. The purpose of this study was to investigate the quality of life and diabetes self-management behaviors in ethnically diverse older adults with type 2 diabetes. The SF-12v2 was used to measure physical and mental health quality of life. Scores were compared to general, age sub-groups, and diabetes-specific norms. The Transtheoretical Model (TTM) was applied to assess perceived versus actual behavior for three diabetes self-management tasks: dietary management, medication management, and blood glucose self-monitoring. Dietary intake and hemoglobin A1c values were measured as outcome variables. Utilizing a cross-sectional research design, participants were recruited from Elderly Nutrition Program congregate meal sites (n = 148, mean age 75). ^ Results showed that mean scores of the SF-12v2 were significantly lower in the study sample than the general norms for physical health (p < .001), mental health (p < .01), age sub-group norms (p < .05), and diabetes-specific norms for physical health (p < .001). A multiple regression analysis found that adherence to an exercise plan was significantly associated with better physical health (p < .001). Transtheoretical Model multiple regression analyses explained 68% of the variance for % Kcal from fat, 41% for fiber, 70% for % Kcal from carbohydrate, and 7% for hemoglobin A 1c values. Significant associations were found between TTM stage of change and dietary fiber intake (p < .01). Other significant associations related to diet included gender (p < .01), ethnicity (p < .05), employment (p < .05), type of insurance (p < .05), adherence to an exercise plan (p < .05), number of doctor visits/year ( p < .01), and physical health (p < .05). Significant associations were found between hemoglobin A1c values and age ( p < .05), being non-Hispanic Black (p < .01), income (p < .01), and eye problems (p < .05). ^ The study highlights the importance of the beneficial effects of exercise on quality of life issues. Furthermore, application of the Transtheoretical Model in conjunction with an assessment of dietary intake may be valuable in helping individuals make lifestyle changes. ^

Numerical study of the enlarged O(5) symmetry of the 3D antiferromagnetic RP^(2) spin model

We investigate by means of Monte Carlo simulation and finite-size scaling analysis the critical properties of the three dimensional O (5) non-linear σ model and of the antiferromagnetic RP^(2) model, both of them regularized on a lattice. High accuracy estimates are obtained for the critical exponents, universal dimensionless quantities and critical couplings. It is concluded that both models belong to the same universality class, provided that rather non-standard identifications are made for the momentum-space propagator of the RP^(2) model. We have also investigated the phase diagram of the RP^(2) model extended by a second-neighbor interaction. A rich phase diagram is found, where most of the phase transitions are of the first order.