A Bayesian approach for dose-escalation in a phase I clinical trial incorporating pharmacodynamic endpoints

Bayesian decision procedures have already been proposed for and implemented in Phase I dose-escalation studies in healthy volunteers. The procedures have been based on pharmacokinetic responses reflecting the concentration of the drug in blood plasma and are conducted to learn about the dose-response relationship while avoiding excessive concentrations. However, in many dose-escalation studies, pharmacodynamic endpoints such as heart rate or blood pressure are observed, and it is these that should be used to control dose-escalation. These endpoints introduce additional complexity into the modeling of the problem relative to pharmacokinetic responses. Firstly, there are responses available following placebo administrations. Secondly, the pharmacodynamic responses are related directly to measurable plasma concentrations, which in turn are related to dose. Motivated by experience of data from a real study conducted in a conventional manner, this paper presents and evaluates a Bayesian procedure devised for the simultaneous monitoring of pharmacodynamic and pharmacokinetic responses. Account is also taken of the incidence of adverse events. Following logarithmic transformations, a linear model is used to relate dose to the pharmacokinetic endpoint and a quadratic model to relate the latter to the pharmacodynamic endpoint. A logistic model is used to relate the pharmacokinetic endpoint to the risk of an adverse event.

High-throughput proteomics using matrix-assisted laser desorption/ ionization mass spectrometry

It has become evident that the mystery of life will not be deciphered just by decoding its blueprint, the genetic code. In the life and biomedical sciences, research efforts are now shifting from pure gene analysis to the analysis of all biomolecules involved in the machinery of life. One area of these postgenomic research fields is proteomics. Although proteomics, which basically encompasses the analysis of proteins, is not a new concept, it is far from being a research field that can rely on routine and large-scale analyses. At the time the term proteomics was coined, a gold-rush mentality was created, promising vast and quick riches (i.e., solutions to the immensely complex questions of life and disease). Predictably, the reality has been quite different. The complexity of proteomes and the wide variations in the abundances and chemical properties of their constituents has rendered the use of systematic analytical approaches only partially successful, and biologically meaningful results have been slow to arrive. However, to learn more about how cells and, hence, life works, it is essential to understand the proteins and their complex interactions in their native environment. This is why proteomics will be an important part of the biomedical sciences for the foreseeable future. Therefore, any advances in providing the tools that make protein analysis a more routine and large-scale business, ideally using automated and rapid analytical procedures, are highly sought after. This review will provide some basics, thoughts and ideas on the exploitation of matrix-assisted laser desorption/ ionization in biological mass spectrometry - one of the most commonly used analytical tools in proteomics - for high-throughput analyses.

High-throughput proteomics using matrix-assisted laser desorption/ionization mass spectrometry

It has become evident that the mystery of life will not be deciphered just by decoding its blueprint, the genetic code. In the life and biomedical sciences, research efforts are now shifting from pure gene analysis to the analysis of all biomolecules involved in the machinery of life. One area of these postgenomic research fields is proteomics. Although proteomics, which basically encompasses the analysis of proteins, is not a new concept, it is far from being a research field that can rely on routine and large-scale analyses. At the time the term proteomics was coined, a gold-rush mentality was created, promising vast and quick riches (i.e., solutions to the immensely complex questions of life and disease). Predictably, the reality has been quite different. The complexity of proteomes and the wide variations in the abundances and chemical properties of their constituents has rendered the use of systematic analytical approaches only partially successful, and biologically meaningful results have been slow to arrive. However, to learn more about how cells and, hence, life works, it is essential to understand the proteins and their complex interactions in their native environment. This is why proteomics will be an important part of the biomedical sciences for the foreseeable future. Therefore, any advances in providing the tools that make protein analysis a more routine and large-scale business, ideally using automated and rapid analytical procedures, are highly sought after. This review will provide some basics, thoughts and ideas on the exploitation of matrix-assisted laser desorption/ionization in biological mass spectrometry - one of the most commonly used analytical tools in proteomics - for high-throughput analyses.

Knowledge sharing: Context, confusion and controversy

Project managers in the construction industry increasingly seek to learn from other industrial sectors. Knowledge sharing between different contexts is thus viewed as an essential source of competitive advantage. It is important therefore for project managers from all sectors to address and develop appropriate methods of knowledge sharing. However, too often it is assumed that knowledge freely exists and can be captured and shared between contexts. Such assumptions belie complexities and problems awaiting the unsuspecting knowledge-sharing protagonist. Knowledge per se is a problematic esoteric concept that does not lend itself easily to codification. Specifically tacit knowledge possessed by individuals, presents particular methodological issues for those considering harnessing its utility in return for competitive advantage. The notion that knowledge is also embedded in specific social contexts compounds this complexity. It is argued that knowledge is highly individualistic and concomitant with the various surrounding contexts within which it is shaped and enacted. Indeed, these contexts are also shaped as a consequence of knowledge adding further complexity to the problem domain. Current methods of knowledge capture, transfer and, sharing fall short of addressing these problematic issues. Research is presented that addresses these problems and proposes an alternative method of knowledge sharing. Drawing on data and observations collected from its application, the findings clearly demonstrate the crucial role of re-contextualisation, social interaction and dialectic debate in understanding knowledge sharing.

Introducing assistive technology into the homes of older people: Some lessons from the Netherlands - A case study

The authors have just completed a study of assistive technology (AT) and how it can be introduced into the existing homes of older people. As part of this empirical study some collaboration with the Netherlands took place for two reasons. First to learn about the use of assistive technology from a country where its creative use was well established and second to learn how older people influence policy. Two Dutch consultants helped the team and a short visit was paid to Eindhoven. As a result of this collaboration new ways of using AT were found and comparisons made with the policy and legislative background. In addition lessons were drawn about the involvement of older people.

Teachers as researchers and teachers as software developers: how use-case analysis helps build better educational software

A series of government initiatives has raised both the profile of ICT in the curriculum and the expectation that high quality teaching and learning resources will be accessible across electronic networks. In order for e-learning resources such as websites to have the maximum educational impact, teachers need to be involved in their design and development. Use-case analysis provides a means of defining user requirements and other constraints in such a way that software developers can produce e-learning resources which reflect teachers' professional knowledge and support their classroom practice. It has some features in common with the participatory action research used to develop other aspects of classroom practice. Two case-studies are presented: one involves the development of an on-line resource centred on transcripts of original historical documents; the other describes how 'Learning how to Learn', a major, distributed research project funded under the ESRC Teaching and Learning Research Programme is using use-case analysis to develop web resources and services.

'Word-learning wizardry' at I;6

This article explores whether infants are able to learn words as rapidly as has been reported for preschoolers. Sixty-four infants aged 1;6 were taught labels for either two moving images or two still images. Each image-label pair was presented three times, after which comprehension was assessed using an adaptation of the intermodal preferential looking paradigm. Three repetitions of each label were found to be sufficient for learning to occur, fewer than has previously been reported for infants under two years. Moreover, contrary to a previous finding, learning was equally rapid for infants who were taught labels for moving versus still images. The findings indicate that infants in the early stages of acquiring a vocabulary learn new word-referent associations with ease, and that the learning conditions that allow such learning are less restricted that was previously believed.

The use of social and salience cues in early word learning

This article explores young infants' ability to learn new words in situations providing tightly controlled social and salience cues to their reference. Four experiments investigated whether, given two potential referents, 15-month-olds would attach novel labels to (a) an image toward which a digital recording of a face turned and gazed, (b) a moving image versus a stationary image, (c) a moving image toward which the face gazed, and (d) a gazed-on image versus a moving image. Infants successfully used the recorded gaze cue to form new word-referent associations and also showed learning in the salience condition. However, their behavior in the salience condition and in the experiments that followed suggests that, rather than basing their judgments of the words' reference on the mere presence or absence of the referent's motion, infants were strongly biased to attend to the consistency with which potential referents moved when a word was heard. (c) 2006 Elsevier Inc. All rights reserved.

The role of perirhinal cortex in visual discrimination learning for visual secondary reinforcement in rats

Perirhinal cortex in monkeys has been thought to be involved in visual associative learning. The authors examined rats' ability to make associations between visual stimuli in a visual secondary reinforcement task. Rats learned 2-choice visual discriminations for secondary visual reinforcement. They showed significant learning of discriminations before any primary reinforcement. Following bilateral perirhinal cortex lesions, rats continued to learn visual discriminations for visual secondary reinforcement at the same rate as before surgery. Thus, this study does not support a critical role of perirhinal cortex in learning for visual secondary reinforcement. Contrasting this result with other positive results, the authors suggest that the role of perirhinal cortex is in "within-object" associations and that it plays a much lesser role in stimulus-stimulus associations between objects.

Dynamic automata for mobile robot learning

Researchers at the University of Reading have developed over many years some simple mobile robots that explore an environment they perceive through simple ultrasonic sensors. Information from these sensors has allowed the robots to learn the simple task of moving around while avoiding dynamic obstacles using a static set of fuzzy automata, the choice of which has been criticised, due to its arbitrary nature. This paper considers how a dynamic set of automata can overcome this criticism. In addition, a new reinforcement learning function is outlined which is both scalable to different numbers and types of sensors. The innovations compare successfully with earlier work.

Learning how older adults undertake computer tasks [poster]

This paper describes a study that was conducted to learn more about how older adults use the tools in a GUI to undertake tasks in Windows applications. The objective was to gain insight into what people did and what they found most difficult. File and folder manipulation, and some aspects of formatting presented difficulties, and these were thought to be related to a lack of understanding of the task model, the correct interpretation of the visual cues presented by the interface, and the recall and translation of the task model into a suitable sequence of actions.

e-learning in project management using simulation models: a case study based on the replication of an experiment

Current e-learning systems are increasing their importance in higher education. However, the state of the art of e-learning applications, besides the state of the practice, does not achieve the level of interactivity that current learning theories advocate. In this paper, the possibility of enhancing e-learning systems to achieve deep learning has been studied by replicating an experiment in which students had to learn basic software engineering principles. One group learned these principles using a static approach, while the other group learned the same principles using a system-dynamics-based approach, which provided interactivity and feedback. The results show that, quantitatively, the latter group achieved a better understanding of the principles; furthermore, qualitatively, they enjoyed the learning experience

Shaking hands: Priming by social action effects

In a semi-naturalistic response-effect compatibility paradigm, participants were given the opportunity to learn that hand-shaking actions would be followed by social effects (human hand-shaking stimuli from a third-person perspective) or inanimate effects (block arrow stimuli). Relative to the actions, these effects appeared on the same or the opposite side of the screen (positional compatibility), and pointed towards or away from the response hand (directional compatibility). After learning, response times indicated a positional compatibility effect for both social and inanimate effects, but a directional compatibility effect occurred only for social action effects. These findings indicate that actions can be represented, not only by their effects on the inanimate world, but also by their effects on the actions of others. They are consistent with ideomotor theory, and with the view that actions are represented by bidirectional response-effect associations. They also have implications with respect to the origins and on-line control of imitation and the systems supporting imitation.

Design and development of a haptic dental training system - hapTEL

This paper presents a novel design of a virtual dental training system (hapTEL) using haptic technology. The system allows dental students to learn and practice procedures such as dental drilling, caries removal and cavity preparation for tooth restoration. This paper focuses on the hardware design, development and evaluation aspects in relation to the dental training and educational requirements. Detailed discussions on how the system offers dental students a natural operational position are documented. An innovative design of measuring and connecting the dental tools to the haptic device is also shown. Evaluation of the impact on teaching and learning is discussed.

Remote control systems laboratory

Control systems theory can be a discipline difficult to learn without some laboratory help. With the help of focused laboratories this discipline turns to be very interesting to the students involved. The main problem is that laboratories aren't always available to students, and sometimes, when they are available, aren't big enough to a growing student population. Thus, with computer networks growing so fast, why don't create remote control labs that can be used by a large number of students? Why don't create remote control labs using Internetⓒ Copyright ?2001 IFAC Keywords: Remote Control, Computer Networks, Database, Educational Aids, Laboratory Education, Communication Control Applications.