Tear film lipids:dynamic composition and clinical performance

Purpose: Meibomian-derived lipid secretions are well characterised but their subsequent fate in the ocular environment is less well understood. Phospholipids are thought to facilitate the interface between aqueous and lipid layers of the tear film and to be involved in ocular lubrication processes. We have extended our previous studies on phospholipid levels in the tear film to encompass the fate of polar and non-polar lipids in progressive accumulation and aging processes on both conventional and silicone-modified hydrogel lenses. This is an important aspect of the developing understanding of the role of lipids in the clinical performance of silicone hydrogels. Method: Several techniques were used to identify lipids in the tear film. Mass-spectrometric methods included Agilent 1100-based liquid chromatography coupled to mass spectrometry (LCMS) and Perkin Elmer gas chromatography mass spectrometry (GCMS). Thin layer chromatography (TLC) was used for separation of lipids on the basis of increasing solvent polarity. Routine assay of lipid extractions from patient-worn lenses was carried out using a Hewlett Packard 1090 liquid chromatograph coupled to both uv and Agilent 1100 fluorescence detection. A range of histological together with optical, and electron microscope techniques was used in deposit analysis. Results: Progressive lipid uptake was assessed in various ways, including: composition changes with wear time, differential lipid penetrate into the lens matrix and, particularly, the extent to which lipids become unextractable as a function of wear time. Solvent-based separation and HPLC gave consistent results indicating that the polarity of lipid classes decreased as follows: phospholipids/fatty acids > triglycerides > cholesterol/cholesteryl esters. Tear lipids were found to show autofluorescence—which underpinned the value of fluorescence microscopy and fluorescence detection coupled with HPLC separation. The most fluorescent lipids were found to be cholesteryl esters; histological techniques coupled with fluorescence microscopy indicated that white spots (’’jelly bumps’’) formed on silicone hydrogel lenses contain a high proportion of cholesteryl esters. Lipid profiles averaged for 30 symptomatic and 30 asymptomatic contact lens wearers were compiled. Peak classes were split into: cholesterol (C), cholesteryl esters (CE), glycerides (G), polar fatty acids/phospholipids (PL). The lipid ratio for ymptomatic/symptomatic was 0.6 ± 0.1 for all classes except one—the cholesterol ratio was 0.2 ± 0.05. Significantly the PL ratio was no different from that of any other class except cholesterol. Chromatography indicated that: lipid polarity decreased with depth of penetration and that lipid extractability decreased with wear time. Conclusions: Meibomian lipid composition differs from that in the tear film and on worn lenses. Although the same broad lipid classes were obtained by extraction from all lenses and all patients studied, quantities vary with wear and material. Lipid extractability diminishes with wear time regardless of the use of cleaning regimes. Dry eye symptoms in contact lens wear are frequently linked to lipid layer behaviour but seem to relate more to total lipid than to specific composition. Understanding the detail of lipid related processes is an important element of improving the clinical performance of materials and care solutions.

Measurement of productivity index with dynamic DEA

Fare, Grosskopf, Norris and Zhang developed a non-parametric productivity index, Malmquist index, using data envelopment analysis (DEA). The Malmquist index is a measure of productivity progress (regress) and it can be decomposed to different components such as 'efficiency catch-up' and 'technology change'. However, Malmquist index and its components are based on two period of time which can capture only a part of the impact of investment in long-lived assets. The effects of lags in the investment process on the capital stock have been ignored in the current model of Malmquist index. This paper extends the recent dynamic DEA model introduced by Emrouznejad and Thanassoulis and Emrouznejad for dynamic Malmquist index. This paper shows that the dynamic productivity results for Organisation for Economic Cooperation and Development countries should reflect reality better than those based on conventional model.

A mathematical model for dynamic efficiency using data envelopment analysis

In this paper we propose a data envelopment analysis (DEA) based method for assessing the comparative efficiencies of units operating production processes where input-output levels are inter-temporally dependent. One cause of inter-temporal dependence between input and output levels is capital stock which influences output levels over many production periods. Such units cannot be assessed by traditional or 'static' DEA which assumes input-output correspondences are contemporaneous in the sense that the output levels observed in a time period are the product solely of the input levels observed during that same period. The method developed in the paper overcomes the problem of inter-temporal input-output dependence by using input-output 'paths' mapped out by operating units over time as the basis of assessing them. As an application we compare the results of the dynamic and static model for a set of UK universities. The paper is suggested that dynamic model capture the efficiency better than static model. © 2003 Elsevier Inc. All rights reserved.

Environmental scanning electron microscopy offers real-time morphological analysis of liposomes and niosomes

Liposomes have been imaged using a plethora of techniques. However, few of these methods offer the ability to study these systems in their natural hydrated state without the requirement of drying, staining, and fixation of the vesicles. However, the ability to image a liposome in its hydrated state is the ideal scenario for visualization of these dynamic lipid structures and environmental scanning electron microscopy (ESEM), with its ability to image wet systems without prior sample preparation, offers potential advantages to the above methods. In our studies, we have used ESEM to not only investigate the morphology of liposomes and niosomes but also to dynamically follow the changes in structure of lipid films and liposome suspensions as water condenses on to or evaporates from the sample. In particular, changes in liposome morphology were studied using ESEM in real time to investigate the resistance of liposomes to coalescence during dehydration thereby providing an alternative assay of liposome formulation and stability. Based on this protocol, we have also studied niosome-based systems and cationic liposome/DNA complexes. Copyright © Informa Healthcare.

Emulation of dynamic computer models with multivariate output

This preliminary report describes work carried out as part of work package 1.2 of the MUCM research project. The report is split in two parts: the ?rst part (Sections 1 and 2) summarises the state of the art in emulation of computer models, while the second presents some initial work on the emulation of dynamic models. In the ?rst part, we describe the basics of emulation, introduce the notation and put together the key results for the emulation of models with single and multiple outputs, with or without the use of mean function. In the second part, we present preliminary results on the chaotic Lorenz 63 model. We look at emulation of a single time step, and repeated application of the emulator for sequential predic- tion. After some design considerations, the emulator is compared with the exact simulator on a number of runs to assess its performance. Several general issues related to emulating dynamic models are raised and discussed. Current work on the larger Lorenz 96 model (40 variables) is presented in the context of dimension reduction, with results to be provided in a follow-up report. The notation used in this report are summarised in appendix.

Run-time connector synthesis for autonomic systems of systems

A key objective of autonomic computing is to reduce the cost and expertise required for the management of complex IT systems. As a growing number of these systems are implemented as hierarchies or federations of lower-level systems, techniques that support the development of autonomic systems of systems are required. This article introduces one such technique, which involves the run-time synthesis of autonomic system connectors. These connectors are specified by means of a new type of autonomic computing policy termed a resource definition policy, and enable the dynamic realisation of collections of collaborating autonomic systems, as envisaged by the original vision of autonomic computing. We propose a framework for the formal specification of autonomic computing policies, and use it to define the new policy type and to describe its application to the development of autonomic system of systems. To validate the approach, we present a sample data-centre application that was built using connectors synthesised from resource-definition policies.

A study of the dynamic behaviour of a pulsed column solvent extraction plant

A study has been made of the dynamic behaviour of a nuclear fuel reprocessing plant utilising pulsed solvent extraction columns. A flowsheet is presented and the choice of an extraction device is discussed. The plant is described by a series of modules each module representing an item of equipment. Each module consists of a series of differential equations describing the dynamic behaviour of the equipment. The model is written in PMSP, a language developed for dynamic simulation models. The differential equations are solved to predict plant behaviour with time. The dynamic response of the plant to a range of disturbances has been assessed. The interactions between pulsed columns have been demonstrated and illustrated. The importance of auxillary items of equipment to plant performance is demonstrated. Control of the reprocessing plant is considered and the effect of control parameters on performance assessed.

Hidden state models for time series

Amongst all the objectives in the study of time series, uncovering the dynamic law of its generation is probably the most important. When the underlying dynamics are not available, time series modelling consists of developing a model which best explains a sequence of observations. In this thesis, we consider hidden space models for analysing and describing time series. We first provide an introduction to the principal concepts of hidden state models and draw an analogy between hidden Markov models and state space models. Central ideas such as hidden state inference or parameter estimation are reviewed in detail. A key part of multivariate time series analysis is identifying the delay between different variables. We present a novel approach for time delay estimating in a non-stationary environment. The technique makes use of hidden Markov models and we demonstrate its application for estimating a crucial parameter in the oil industry. We then focus on hybrid models that we call dynamical local models. These models combine and generalise hidden Markov models and state space models. Probabilistic inference is unfortunately computationally intractable and we show how to make use of variational techniques for approximating the posterior distribution over the hidden state variables. Experimental simulations on synthetic and real-world data demonstrate the application of dynamical local models for segmenting a time series into regimes and providing predictive distributions.

Dynamic simulation of chemical plant

This thesis describes the design and implementation of a new dynamic simulator called DASP. It is a computer program package written in standard Fortran 77 for the dynamic analysis and simulation of chemical plants. Its main uses include the investigation of a plant's response to disturbances, the determination of the optimal ranges and sensitivities of controller settings and the simulation of the startup and shutdown of chemical plants. The design and structure of the program and a number of features incorporated into it combine to make DASP an effective tool for dynamic simulation. It is an equation-oriented dynamic simulator but the model equations describing the user's problem are generated from in-built model equation library. A combination of the structuring of the model subroutines, the concept of a unit module, and the use of the connection matrix of the problem given by the user have been exploited to achieve this objective. The Executive program has a structure similar to that of a CSSL-type simulator. DASP solves a system of differential equations coupled to nonlinear algebraic equations using an advanced mixed equation solver. The strategy used in formulating the model equations makes it possible to obtain the steady state solution of the problem using the same model equations. DASP can handle state and time events in an efficient way and this includes the modification of the flowsheet. DASP is highly portable and this has been demonstrated by running it on a number of computers with only trivial modifications. The program runs on a microcomputer with 640 kByte of memory. It is a semi-interactive program, with the bulk of all input data given in pre-prepared data files with communication with the user is via an interactive terminal. Using the features in-built in the package, the user can view or modify the values of any input data, variables and parameters in the model, and modify the structure of the flowsheet of the problem during a simulation session. The program has been demonstrated and verified using a number of example problems.

Time scale analysis for fluidizedbedmeltgranulation-II: binder spreading rate

The spreading time of liquid binder droplet on the surface a primary particle is analyzed for Fluidized Bed Melt Granulation (FBMG). As discussed in the first paper of this series (Chua et al., in press) the droplet spreading rate has been identified as one of the important parameters affecting the probability of particles aggregation in FBMG. In this paper, the binder droplet spreading time has been estimated using Computational Fluid Dynamic modeling (CFD) based on Volume of Fluid approach (VOF). A simplified analytical solution has been developed and tested to explore its validity for predicting the spreading time. For the purpose of models validation, the droplet spreading evolution was recorded using a high speed video camera. Based on the validated model, a generalized correlative equation for binder spreading time is proposed. For the operating conditions considered here, the spreading time for Polyethylene Glycol (PEG1500) binder was found to fall within the range of 10-2 to 10-5 s. The study also included a number of other common binders used in FBMG. The results obtained here will be further used in paper III, where the binder solidification rate is discussed.

An investigation of the dynamic characteristics of a bolted-rotor system

A Jeffcott rotor consists of a disc at the centre of an axle supported at its end by bearings. A bolted Jeffcott rotor is formed by two discs, each with a shaft on one side. The discs are held together by spring loaded bolts near the outer edge. When the rotor turns there is tendency for the discs to separate on one side. This effect is more marked if the rotor is unbalanced, especially at resonance speeds. The equations of motion of the system have been developed with four degrees of freedom to include the rotor and bearing movements in the respective axes. These equations which include non-linear terms caused by the rotor opening, are subjected to external force such from rotor imbalance. A simulation model based on these equations was created using SIMULINK. An experimental test rig was used to characterise the dynamic features. Rotor discs open at a lateral displacement of the rotor of 0.8 mm. This is the threshold value used to show the change of stiffness from high stiffness to low stiffness. The experimental results, which measure the vibration amplitude of the rotor, show the dynamic behaviour of the bolted rotor due to imbalance. Close agreement of the experimental and theoretical results from time histories, waterfall plots, pseudo-phase plots and rotor orbit plot, indicated the validity of the model and existence of the non-linear jump phenomenon.

Neural network enhanced self tuning adaptive control application for non-linear control of dynamic systems

The main theme of research of this project concerns the study of neutral networks to control uncertain and non-linear control systems. This involves the control of continuous time, discrete time, hybrid and stochastic systems with input, state or output constraints by ensuring good performances. A great part of this project is devoted to the opening of frontiers between several mathematical and engineering approaches in order to tackle complex but very common non-linear control problems. The objectives are: 1. Design and develop procedures for neutral network enhanced self-tuning adaptive non-linear control systems; 2. To design, as a general procedure, neural network generalised minimum variance self-tuning controller for non-linear dynamic plants (Integration of neural network mapping with generalised minimum variance self-tuning controller strategies); 3. To develop a software package to evaluate control system performances using Matlab, Simulink and Neural Network toolbox. An adaptive control algorithm utilising a recurrent network as a model of a partial unknown non-linear plant with unmeasurable state is proposed. Appropriately, it appears that structured recurrent neural networks can provide conveniently parameterised dynamic models for many non-linear systems for use in adaptive control. Properties of static neural networks, which enabled successful design of stable adaptive control in the state feedback case, are also identified. A survey of the existing results is presented which puts them in a systematic framework showing their relation to classical self-tuning adaptive control application of neural control to a SISO/MIMO control. Simulation results demonstrate that the self-tuning design methods may be practically applicable to a reasonably large class of unknown linear and non-linear dynamic control systems.

Dynamic ocular thermography

The ability to measure ocular surface temperature (OST) with thermal imaging offers potential insight into ocular physiology that has been acknowledged in the literature. The TH7102MX thermo-camera (NEC San-ei, Japan) continuously records dynamic information about OST without sacrificing spatial resolution. Using purpose-designed image analysis software, it was possible to select and quantify the principal components of absolute temperature values and the magnitude plus rate of temperature change that followed blinking. The techniques was examined for repeatability, reproducibility and the effects of extrinsic factors: a suitable experimental protocol was thus developed. The precise source of the measured thermal radiation has previously been subject toe dispute: in this thesis, the results of a study examining the relationships between physical parameters of the anterior eye and OST, confirmed a principal role for the tear film in OST. The dynamic changes in OST were studied in a large group of young subjects: quantifying the post-blink changes in temperature with time also established a role for tear flow dynamics in OST. Using dynamic thermography, the effects of hydrogel contact lens wear on OST were investigated: a model eye for in vivo work, and both neophyte and adapted contact lens wearers for in vivo studies. Significantly greater OST was observed in contact lens wearers, particularly with silicone hydrogel lenses compared to etafilcon A, and tended to be greatest when lenses had been worn continuously. This finding is important to understanding the ocular response to contact lens wear. In a group of normal subjects, dynamic thermography appeared to measure the ocular response to the application of artificial tear drops: this may prove to be a significant research and clinical tool.

Dynamic QoS management and optimisation in service-based systems

Service-based systems that are dynamically composed at run time to provide complex, adaptive functionality are currently one of the main development paradigms in software engineering. However, the Quality of Service (QoS) delivered by these systems remains an important concern, and needs to be managed in an equally adaptive and predictable way. To address this need, we introduce a novel, tool-supported framework for the development of adaptive service-based systems called QoSMOS (QoS Management and Optimisation of Service-based systems). QoSMOS can be used to develop service-based systems that achieve their QoS requirements through dynamically adapting to changes in the system state, environment and workload. QoSMOS service-based systems translate high-level QoS requirements specified by their administrators into probabilistic temporal logic formulae, which are then formally and automatically analysed to identify and enforce optimal system configurations. The QoSMOS self-adaptation mechanism can handle reliability- and performance-related QoS requirements, and can be integrated into newly developed solutions or legacy systems. The effectiveness and scalability of the approach are validated using simulations and a set of experiments based on an implementation of an adaptive service-based system for remote medical assistance.

Temporal finite elements in the dynamic analysis of structures

This thesis demonstrates that the use of finite elements need not be confined to space alone, but that they may also be used in the time domain, It is shown that finite element methods may be used successfully to obtain the response of systems to applied forces, including, for example, the accelerations in a tall structure subjected to an earthquake shock. It is further demonstrated that at least one of these methods may be considered to be a practical alternative to more usual methods of solution. A detailed investigation of the accuracy and stability of finite element solutions is included, and methods of applications to both single- and multi-degree of freedom systems are described. Solutions using two different temporal finite elements are compared with those obtained by conventional methods, and a comparison of computation times for the different methods is given. The application of finite element methods to distributed systems is described, using both separate discretizations in space and time, and a combined space-time discretization. The inclusion of both viscous and hysteretic damping is shown to add little to the difficulty of the solution. Temporal finite elements are also seen to be of considerable interest when applied to non-linear systems, both when the system parameters are time-dependent and also when they are functions of displacement. Solutions are given for many different examples, and the computer programs used for the finite element methods are included in an Appendix.