Principles and clinical application of assessing alterations in renal elimination pathways

Drugs and metabolites are eliminated from the body by metabolism and excretion. The kidney makes the major contribution to excretion of unchanged drug and also to excretion of metabolites. Net renal excretion is a combination of three processes - glomerular filtration, tubular secretion and tubular reabsorption. Renal function has traditionally been determined by measuring plasma creatinine and estimating creatinine clearance. However, estimated creatinine clearance measures only glomerular filtration with a small contribution from active secretion. There is accumulating evidence of poor correlation between estimated creatinine clearance and renal drug clearance in different clinical settings, challenging the 'intact nephron hypothesis' and suggesting that renal drug handling pathways may not decline in parallel. Furthermore, it is evident that renal drug handling is altered to a clinically significant extent in a number of disease states, necessitating dosage adjustment not just based on filtration. These observations suggest that a re-evaluation of markers of renal function is required. Methods that measure all renal handling pathways would allow informed dosage individualisation using an understanding of renal excretion pathways and patient characteristics. Methodologies have been described to determine individually each of the renal elimination pathways. However, their simultaneous assessment has only recently been investigated. A cocktail of markers to measure simultaneously the individual renal handling pathways have now been developed, and evaluated in healthy volunteers. This review outlines the different renal elimination pathways and the possible markers that can be used for their measurement. Diseases and other physiological conditions causing altered renal drug elimination are presented, and the potential application of a cocktail of markers for the simultaneous measurement of drug handling is evaluated. Further investigation of the effects of disease processes on renal drug handling should include people with HIV infection, transplant recipients (renal and liver) and people with rheumatoid arthritis. Furthermore, changes in renal function in the elderly, the effect of sex on renal function, assessment of living kidney donors prior to transplantation and the investigation of renal drug interactions would also be potential applications. Once renal drug handling pathways are characterised in a patient population, the implications for accurate dosage individualisation can be assessed. The simultaneous measurement of renal function elimination pathways of drugs and metabolites has the potential to assist in understanding how renal function changes with different disease states or physiological conditions. In addition, it will further our understanding of fundamental aspects of the renal elimination of drugs.

Destination image, romance and place experience - an application of intimacy theory in tourism

In some forms of tourism, and perhaps particularly in the case of special interest tourism, it can be argued that tourism encounters are service relationships with emotional attachment through the special interest focus and a level of enduring involvement on the part of participants. This involvement is two-fold. First, an interest with the activity; second, a sharing with like-minded people in a social world that extends from home to tourist destination and return. Intimacies in tourism can thus be interpreted through the model of the relationship cycle that comprises the stages A. Aquaintance, B, Buildup, C, Continuation and D, Dissolution. The paper builds upon this concept by utilising ideas of other-centred and self-centredness in personal relationships, and extends the concept of other-centredness to host environments. It also suggests that, in the academic literature about place, location may be secondary in that the quality of experience is primarily determined by the intimacies that exist between people at that place, especially that existing between visitors. © 2004 Published by Elsevier Ltd.

Theory and application of inverse problems in groundwater: numerical, laboratory and field studies.

Aquifers are a vital water resource whose quality characteristics must be safeguarded or, if damaged, restored. The extent and complexity of aquifer contamination is related to characteristics of the porous medium, the influence of boundary conditions, and the biological, chemical and physical processes. After the nineties, the efforts of the scientists have been increased exponentially in order to find an efficient way for estimating the hydraulic parameters of the aquifers, and thus, recover the contaminant source position and its release history. To simplify and understand the influence of these various factors on aquifer phenomena, it is common for researchers to use numerical and controlled experiments. This work presents some of these methods, applying and comparing them on data collected during laboratory, field and numerical tests. The work is structured in four parts which present the results and the conclusions of the specific objectives.

Is there a trade-off between quality and productivity? The case of diagnostic technologies in Portugal

The purpose of this paper is twofold: first, we compute quality-adjusted measures of productivity change for the three most important diagnostic technologies (i.e., the Computerised Tomography Scan, Electrocardiogram and Echocardiogram) in the major Portuguese hospitals. We use the Malmquist–Luenberger index, which allows to measure productivity growth while controlling for the quality of the production. Second, using non-parametric tests, we analyse whether the implementation of the Prospective Payment System may have had a positive impact on the movements of productivity over time. The results show that the PPS has helped hospitals to use these tools more efficiently and to improve their effectiveness.

Has DRG payment influenced the technical efficiency and productivity of diagnostic technologies in Portuguese public hospitals? An empirical analysis using parametric and non‐parametric methods

The use of Diagnosis Related Groups (DRG) as a mechanism for hospital financing is a currently debated topic in Portugal. The DRG system was scheduled to be initiated by the Health Ministry of Portugal on January 1, 1990 as an instrument for the allocation of public hospital budgets funded by the National Health Service (NHS), and as a method of payment for other third party payers (e.g., Public Employees (ADSE), private insurers, etc.). Based on experience from other countries such as the United States, it was expected that implementation of this system would result in more efficient hospital resource utilisation and a more equitable distribution of hospital budgets. However, in order to minimise the potentially adverse financial impact on hospitals, the Portuguese Health Ministry decided to gradually phase in the use of the DRG system for budget allocation by using blended hospitalspecific and national DRG casemix rates. Since implementation in 1990, the percentage of each hospitals budget based on hospital specific costs was to decrease, while the percentage based on DRG casemix was to increase. This was scheduled to continue until 1995 when the plan called for allocating yearly budgets on a 50% national and 50% hospitalspecific cost basis. While all other nonNHS third party payers are currently paying based on DRGs, the adoption of DRG casemix as a National Health Service budget setting tool has been slower than anticipated. There is now some argument in both the political and academic communities as to the appropriateness of DRGs as a budget setting criterion as well as to their impact on hospital efficiency in Portugal. This paper uses a twostage procedure to assess the impact of actual DRG payment on the productivity (through its components, i.e., technological change and technical efficiency change) of diagnostic technology in Portuguese hospitals during the years 1992–1994, using both parametric and nonparametric frontier models. We find evidence that the DRG payment system does appear to have had a positive impact on productivity and technical efficiency of some commonly employed diagnostic technologies in Portugal during this time span.

A practical study of the application of computer techniques in processes of musical composition

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The application of monolayer studies in the understanding of liposomal formulations

The study of surfactant monolayers is certainly not a new technique, but the application of monolayer studies to elucidate controlling factors in liposome design remains an underutilised resource. Using a Langmuir-Blodgett trough, pure and mixed lipid monolayers can be investigated, both for their interactions within the monolayer, and for interfacial interactions with drugs in the aqueous sub-phase. Despite these monolayers effectively being only half a bilayer, with a flat rather than curved structure, information from these studies can be effectively translated into liposomal systems. Here we outline the background, general protocols and application of Langmuir studies with a focus on their application in liposomal systems. A range of case studies are discussed which show how the system can be used to support its application in the development of liposome drug delivery. Examples include investigations into the effect of cholesterol within the liposome bilayer, understanding effective lipid packaging within the bilayer to promote water soluble and poorly soluble drug retention, the effect of alkyl chain length on lipid packaging, and drug-monolayer electrostatic interactions that promote bilayer repackaging.

Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

Application of SOA-NOLM in all-optical processing

This thesis presents experimental investigations of the use of semiconductor optical amplifiers in a nonlinear loop mirror (SOA-NOLM) and its application in all-optical processing. The techniques used are mainly experimental and are divided into three major applications. Initially the semiconductor optical amplifier, SOA, is experimentally characterised and the optimum operating condition is identified. An interferometric switch based on a Sagnac loop with the SOA as the nonlinear element is employed to realise all-optical switching. All-optical switching is a very attractive alternative to optoelectronic conversion because it avoids the conversion from the optical to the electronic domain and back again. The first major investigation involves a carrier suppressed return to zero, CSRZ, format conversion and transmission. This study is divided into single channel and four channel WDM respectively. The optical bandwidth which limits the conversion is investigated. The improvement of the nonlinear tolerance in the CSRZ transmission is shown which shows the suitability of this format for enhancing system performance. Second, a symmetrical switching window is studied in the SOA-NOLM where two similar control pulses are injected into the SOA from opposite directions. The switching window is symmetric when these two control pulses have the same power and arrive at the same time in the SOA. Finally, I study an all-optical circulating shift register with an inverter. The detailed behaviour of the blocks of zeros and ones has been analysed in terms of their transient measurement. Good agreement with a simple model of the shift register is obtained. The transient can be reduced but it will affect the extinction ratio of the pulses.

An application of linear programming in the pottery industry

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Delimited Massively Parallel Algorithm Based on Rules Elimination for Application of Active Rules in Transition P Systems

In the field of Transition P systems implementation, it has been determined that it is very important to determine in advance how long takes evolution rules application in membranes. Moreover, to have time estimations of rules application in membranes makes possible to take important decisions related to hardware / software architectures design. The work presented here introduces an algorithm for applying active evolution rules in Transition P systems, which is based on active rules elimination. The algorithm complies the requisites of being nondeterministic, massively parallel, and what is more important, it is time delimited because it is only dependant on the number of membrane evolution rules.

HW Implementation of a Optimized Algorithm for the Application of Active Rules in a Transition P-system

P systems or Membrane Computing are a type of a distributed, massively parallel and non deterministic system based on biological membranes. They are inspired in the way cells process chemical compounds, energy and information. These systems perform a computation through transition between two consecutive configurations. As it is well known in membrane computing, a configuration consists in a m-tuple of multisets present at any moment in the existing m regions of the system at that moment time. Transitions between two configurations are performed by using evolution rules which are in each region of the system in a non-deterministic maximally parallel manner. This work is part of an exhaustive investigation line. The final objective is to implement a HW system that evolves as it makes a transition P-system. To achieve this objective, it has been carried out a division of this generic system in several stages, each of them with concrete matters. In this paper the stage is developed by obtaining the part of the system that is in charge of the application of the active rules. To count the number of times that the active rules is applied exist different algorithms. Here, it is presents an algorithm with improved aspects: the number of necessary iterations to reach the final values is smaller than the case of applying step to step each rule. Hence, the whole process requires a minor number of steps and, therefore, the end of the process will be reached in a shorter length of time.

Study of the Application of Neural Networks in Internet Traffic Engineering

In this study, we showed various approachs implemented in Artificial Neural Networks for network resources management and Internet congestion control. Through a training process, Neural Networks can determine nonlinear relationships in a data set by associating the corresponding outputs to input patterns. Therefore, the application of these networks to Traffic Engineering can help achieve its general objective: “intelligent” agents or systems capable of adapting dataflow according to available resources. In this article, we analyze the opportunity and feasibility to apply Artificial Neural Networks to a number of tasks related to Traffic Engineering. In previous sections, we present the basics of each one of these disciplines, which are associated to Artificial Intelligence and Computer Networks respectively.