This article summarizes the main changes that have occurred in cyclosporin (ciclosporin) monitoring and measurement since the previous review in this journal. Cyclosporin has been reformulated to reduce variability in its absorption, leading to fewer post-transplant rejection episodes. Monitoring has mostly utilized the measurement of pre-dose blood levels of the drug, but more recently the potential benefit of using samples collected during the first few hours post-dose has been evaluated. Calculating the area under the cyclosporin concentration-time curve may be the ideal, but is not viable in the routine clinical situation and 2-h post-dose sampling seems likely to offer a practical clinical solution. Analytical methods based on high-performance liquid chromatography (HPLC) and immunoassay are available for the determination of whole blood cyclosporin concentrations. HPLC is specific but rarely used for routine monitoring, although HPLC-tandem mass spectrometry is making the technique more viable. New immunoassays have been introduced, but none are completely specific for the parent drug and all exhibit cross-reactivity towards cyclosporin metabolites. Immunoassays were originally designed for the lower cyclosporin concentrations seen in pre-dose samples, but are being evaluated and modified for determination of the higher concentrations seen 2 h post-dose.

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During the latter decades of the 20th century as products became increasingly complex it became necessary to formalise engineering and product design methods, reputed exponents of which include Gerhard Pahl and Wolfgang Beitz, L. Bruce Archer, Nigel Cross and Stuart Pugh. Pugh's 'total design' method is described as a linear activity in that product manufacture and use are considered but not what happens to the product at the end of life. This chapter discusses the need to update the 'total design' model by comparing the product life cycle and that of the automobile in particular with systems and cycles in the natural world.

Traditionally, when designing a ship the driving issues are seen to be powering, stability, strength and seakeeping. Issues related to ship operations and evolutions are investigated later in the design process, within the constraint of a fixed layout. This can result in operational inefficiencies and limitations, excessive crew numbers and potentially hazardous situations. This paper summarises work by University College London and the University of Greenwich prior to the completion of a three year EPSRC funded research project to integrate the simulation of personnel movement into early stage ship design. This integration is intended to facilitate the assessment of onboard operations while the design is still highly amenable to change.The project brings together the University of Greenwich developed maritimeEXODUS personnel movement simulation software and the SURFCON implementation of the Design Building Block approach to early stage ship design, which originated with the UCL Ship Design Research team and has been implemented within the PARAMARINE ship design system produced by Graphics Research Corporation. Central to the success of this project is the definition of a suitable series of Performance Measures (PM) which can be used to assess the human performance of the design in different operational scenarios.The paper outlines the progress made on deriving the PM from human dynamics criteria measured in simulations and their incorporation into a Human Performance Metric (HPM) for analysis. It describes the production of a series of SURFCON ship designs, based on the Royal Navy's Type 22 Batch 3 frigate, and their analysis using the PARAMARINE and maritimeEXODUS software. Conclusions on the work to date and for the remainder of the project are presented addressing the integration of personnel movement simulation into the preliminary ship design process.