Some considerations on the design of population pharmacokinetic studies

The goal of this manuscript is to introduce a framework for consideration of designs for population pharmacokinetic orpharmacokinetic-pharmacodynamic studies. A standard one compartment pharmacokinetic model with first-order input and elimination is considered. A series of theoretical designs are considered that explore the influence of optimizing the allocation of sampling times, allocating patients to elementary designs, consideration of sparse sampling and unbalanced designs and also the influence of single vs. multiple dose designs. It was found that what appears to be relatively sparse sampling (less blood samples per patient than the number of fixed effects parameters to estimate) can also be highly informative. Overall, it is evident that exploring the population design space can yield many parsimonious designs that are efficient for parameter estimation and that may not otherwise have been considered without the aid of optimal design theory.

An object-oriented designed finite-difference time-domain simulator for electromagnetic analysis and design in MRI - application to high field analyses

This paper presents a finite-difference time-domain (FDTD) simulator for electromagnetic analysis and design applications in MRI. It is intended to be a complete FDTD model of an MRI system including all RF and low-frequency field generating units and electrical models of the patient. The pro-ram has been constructed in an object-oriented framework. The design procedure is detailed and the numerical solver has been verified against analytical solutions for simple cases and also applied to various field calculation problems. In particular, the simulator is demonstrated for inverse RF coil design, optimized source profile generation, and parallel imaging in high-frequency situations. The examples show new developments enabled by the simulator and demonstrate that the proposed FDTD framework can be used to analyze large-scale computational electromagnetic problems in modern MRI engineering. (C) 2004 Elsevier Inc. All rights reserved.

The cyclotides and related macrocyclic peptides as scaffolds in drug design

The applicability of linear peptides as drugs is potentially limited by their susceptibility to proteolytic cleavage and poor bioavailability. Cyclotides are macrocyclic cystine-knotted mini-proteins that have a broad range of bioactivities and are exceptionally stable, being resistant to chemical, thermal and enzymatic degradation. The general limitations of peptides as drugs can potentially be overcome by using the cyclotide framework as a scaffold onto which new activities may be engineered. The potential use of cyclotides and related peptide scaffolds for drug design is evaluated herein, with reference to increasing knowledge of the structures and sequence diversity of natural cyclotides and the emergence of new approaches in protein engineering.

A formal framework for modelling and analysing mobile systems

This paper presents a formal framework for modelling and analysing mobile systems. The framework comprises a collection of models of the dominant design paradigms which are readily extended to incorporate details of particular technologies, i.e., programming languages and their run-time support, and applications. The modelling language is Object-Z, an extension of the well-known Z specification language with explicit support for object-oriented concepts. Its support for object orientation makes Object-Z particularly suited to our task. The system structuring techniques offered by object-orientation are well suited to modelling mobile systems. In addition, inheritance and polymorphism allow us to exploit commonalities in mobile systems by defining more complex models in terms of simpler ones.

A software audit framework for spyware risk mitigation

Our research described in this paper identifies a three part premise relating to the spyware paradigm. Firstly the data suggests spyware is proliferating at an exponential rate. Secondly ongoing research confirms that spyware produces many security risks – including that of privacy/confidentiality breaches via illicit data collection and reporting. Thirdly, anti-spyware controls are improving but are still considered problematic for several reasons. Our research then concludes that control measures to counter this very significant challenge should merit compliance auditing – and this auditing may effectively target the vital message passing performed by all illicit data collection spyware. Our research then evolves into an experiment involving the design and implementation of a software audit tool to conduct the desired compliance auditing. The software audit tool is positioned at the protected network’s gateway. The software audit tool uses ‘phone-home’ IP addresses as spyware signatures to detect the presence of the offending software. The audit tool also has the capability to differentiate legitimate message passing software from that produced by spyware – and ‘learn’ both new spyware signatures and new legitimate message passing profiles. The testing stage of the software has proven successful – albeit using very limited levels of network message passing variety and frequency.

A design pattern for efficient retrieval of large data sets from remote data sources

Retrieving large amounts of information over wide area networks, including the Internet, is problematic due to issues arising from latency of response, lack of direct memory access to data serving resources, and fault tolerance. This paper describes a design pattern for solving the issues of handling results from queries that return large amounts of data. Typically these queries would be made by a client process across a wide area network (or Internet), with one or more middle-tiers, to a relational database residing on a remote server. The solution involves implementing a combination of data retrieval strategies, including the use of iterators for traversing data sets and providing an appropriate level of abstraction to the client, double-buffering of data subsets, multi-threaded data retrieval, and query slicing. This design has recently been implemented and incorporated into the framework of a commercial software product developed at Oracle Corporation.

An Autonomic Framework for Mobile Cloud Computing

This thesis presents the formal definition of a novel Mobile Cloud Computing (MCC) extension of the Networked Autonomic Machine (NAM) framework, a general-purpose conceptual tool which describes large-scale distributed autonomic systems. The introduction of autonomic policies in the MCC paradigm has proved to be an effective technique to increase the robustness and flexibility of MCC systems. In particular, autonomic policies based on continuous resource and connectivity monitoring help automate context-aware decisions for computation offloading. We have also provided NAM with a formalization in terms of a transformational operational semantics in order to fill the gap between its existing Java implementation NAM4J and its conceptual definition. Moreover, we have extended NAM4J by adding several components with the purpose of managing large scale autonomic distributed environments. In particular, the middleware allows for the implementation of peer-to-peer (P2P) networks of NAM nodes. Moreover, NAM mobility actions have been implemented to enable the migration of code, execution state and data. Within NAM4J, we have designed and developed a component, denoted as context bus, which is particularly useful in collaborative applications in that, if replicated on each peer, it instantiates a virtual shared channel allowing nodes to notify and get notified about context events. Regarding the autonomic policies management, we have provided NAM4J with a rule engine, whose purpose is to allow a system to autonomously determine when offloading is convenient. We have also provided NAM4J with trust and reputation management mechanisms to make the middleware suitable for applications in which such aspects are of great interest. To this purpose, we have designed and implemented a distributed framework, denoted as DARTSense, where no central server is required, as reputation values are stored and updated by participants in a subjective fashion. We have also investigated the literature regarding MCC systems. The analysis pointed out that all MCC models focus on mobile devices, and consider the Cloud as a system with unlimited resources. To contribute in filling this gap, we defined a modeling and simulation framework for the design and analysis of MCC systems, encompassing both their sides. We have also implemented a modular and reusable simulator of the model. We have applied the NAM principles to two different application scenarios. First, we have defined a hybrid P2P/cloud approach where components and protocols are autonomically configured according to specific target goals, such as cost-effectiveness, reliability and availability. Merging P2P and cloud paradigms brings together the advantages of both: high availability, provided by the Cloud presence, and low cost, by exploiting inexpensive peers resources. As an example, we have shown how the proposed approach can be used to design NAM-based collaborative storage systems based on an autonomic policy to decide how to distribute data chunks among peers and Cloud, according to cost minimization and data availability goals. As a second application, we have defined an autonomic architecture for decentralized urban participatory sensing (UPS) which bridges sensor networks and mobile systems to improve effectiveness and efficiency. The developed application allows users to retrieve and publish different types of sensed information by using the features provided by NAM4J's context bus. Trust and reputation is managed through the application of DARTSense mechanisms. Also, the application includes an autonomic policy that detects areas characterized by few contributors, and tries to recruit new providers by migrating code necessary to sensing, through NAM mobility actions.

Managing healthcare performance in analytical framework

Purpose – The purpose of the paper is to develop an integrated framework for performance management of healthcare services. Design/methodology/approach – This study develops a performance management framework for healthcare services using a combined analytic hierarchy process (AHP) and logical framework (LOGFRAME). The framework is then applied to the intensive care units of three different hospitals in developing nations. Numerous focus group discussions were undertaken, involving experts from the specific area under investigation. Findings – The study reveals that a combination of outcome, structure and process-based critical success factors and a combined AHP and LOGFRAME-based performance management framework helps manage performance of healthcare services. Practical implications – The proposed framework could be practiced in hospital-based healthcare services. Originality/value – The conventional approaches to healthcare performance management are either outcome-based or process-based, which cannot reveal improvement measures appropriately in order to assure superior performance. Additionally, they lack planning, implementing and evaluating improvement projects that are identified from performance measurement. This study presents an integrated approach to performance measurement and implementing framework of improvement projects.

Managing healthcare quality using logical framework analysis

Purpose - The purpose of this paper is to develop an integrated quality management model that identifies problems, suggests solutions, develops a framework for implementation and helps to evaluate dynamically healthcare service performance. Design/methodology/approach - This study used the logical framework analysis (LFA) to improve the performance of healthcare service processes. LFA has three major steps - problems identification, solution derivation, and formation of a planning matrix for implementation. LFA has been applied in a case-study environment to three acute healthcare services (Operating Room utilisation, Accident and Emergency, and Intensive Care) in order to demonstrate its effectiveness. Findings - The paper finds that LFA is an effective method of quality management of hospital-based healthcare services. Research limitations/implications - This study shows LFA application in three service processes in one hospital. This very limited population sample needs to be extended. Practical implications - The proposed model can be implemented in hospital-based healthcare services in order to improve performance. It may also be applied to other services. Originality/value - Quality improvement in healthcare services is a complex and multi-dimensional task. Although various quality management tools are routinely deployed for identifying quality issues in healthcare delivery, they are not without flaws. There is an absence of an integrated approach, which can identify and analyse issues, provide solutions to resolve those issues, develop a project management framework to implement those solutions. This study introduces an integrated and uniform quality management tool for healthcare services. © Emerald Group Publishing Limited.

A conceptual framework of accounting policy choice under SSAP 20

Purpose - To provide a framework of accounting policy choice associated with the timing of adoption of the UK Statement of Standard Accounting Practice (SSAP) No. 20, "Foreign Currency Translation". The conceptual framework describes the accounting policy choices that firms face in a setting that is influenced by: their financial characteristics; the flexible foreign exchange rates; and the stock market response to accounting decisions. Design/methodology/approach - Following the positive accounting theory context, this paper puts into a framework the motives and choices of UK firms with regard to the adoption or deferment of the adoption of SSAP 20. The paper utilises the theoretical and empirical findings of previous studies to form and substantiate the conceptual framework. Given the UK foreign exchange setting, the framework identifies the initial stage: lack of regulation and flexibility in financial reporting; the intermediate stage: accounting policy choice; and the final stage: accounting choice and policy review. Findings - There are situations where accounting regulation contrasts with the needs and business objectives of firms and vice-versa. Thus, firms may delay the adoption up to the point where the increase in political costs can just be tolerated. Overall, the study infers that firms might have chosen to defer the adoption of SSAP 20 until they reach a certain corporate goal, or the adverse impact (if any) of the accounting change on firms' financial numbers is minimal. Thus, the determination of the timing of the adoption is a matter which is subject to the objectives of the managers in association with the market and economic conditions. The paper suggests that the flexibility in financial reporting, which may enhance the scope for income-smoothing, can be mitigated by the appropriate standardisation of accounting practice. Research limitations/implications - First, the study encompassed a period when firms and investors were less sophisticated users of financial information. Second, it is difficult to ascertain the decisions that firms would have taken, had the pound appreciated over the period of adoption and had the firms incurred translation losses rather than translation gains. Originality/value - This paper is useful to accounting standards setters, professional accountants, academics and investors. The study can give the accounting standard-setting bodies useful information when they prepare a change in the accounting regulation or set an appropriate date for the implementation of an accounting standard. The paper provides significant insight about the behaviour of firms and the associated impacts of financial markets and regulation on the decision-making process of firms. The framework aims to assist the market and other authorities to reduce information asymmetry and to reinforce the efficiency of the market. © Emerald Group Publishing Limited.

Managing people and performance:An evidence based framework applied to health service organizations

People and their performance are key to an organization's effectiveness. This review describes an evidence-based framework of the links between some key organizational influences and staff performance, health and well-being. This preliminary framework integrates management and psychological approaches, with the aim of assisting future explanation, prediction and organizational change. Health care is taken as the focus of this review, as there are concerns internationally about health care effectiveness. The framework considers empirical evidence for links between the following organizational levels: 1. Context (organizational culture and inter-group relations; resources, including staffing; physical environment) 2. People management (HRM practices and strategies; job design, workload and teamwork; employee involvement and control over work; leadership and support) 3. Psychological consequences for employees (health and stress; satisfaction and commitment; knowledge, skills and motivation) 4. Employee behaviour (absenteeism and turnover; task and contextual performance; errors and near misses) 5. Organizational performance; patient care. This review contributes to an evidence base for policies and practices of people management and performance management. Its usefulness will depend on future empirical research, using appropriate research designs, sufficient study power and measures that are reliable and valid.