Polymer-drug conjugates: current status and future trends

Polymer conjugates are nano-sized, multicomponent constructs already in the clinic as anticancer compounds, both as single agents or as elements of combinations. They have the potential to improve pharmacological therapy of a variety of solid tumors. Polymer-drug conjugation promotes passive tumor targeting by the enhanced permeability and retention (EPR) effect and allows for lysosomotropic drug delivery following endocytic capture. In the first part of this review, we analyze the promising results arising from clinical trials of polymer-bound chemotherapy. The experience gained on these studies provides the basis for the development of a more sophisticated second-generation of polymer conjugates. However, many challenges still lay ahead providing scope to develop and refine this field. The "technology platform'' of polymer therapeutics allows the development of both new and exciting polymeric materials, the incorporation of novel bioactive agents and combinations thereof to address recent advances in drug therapy. The rational design of polymer drug conjugates is expected to realize the true potential of these "nanomedicines".

How active gaze informs the hand in sequential pointing movements

Visual information is vital for fast and accurate hand movements. It has been demonstrated that allowing free eye movements results in greater accuracy than when the eyes maintain centrally fixed. Three explanations as to why free gaze improves accuracy are: shifting gaze to a target allows visual feedback in guiding the hand to the target (feedback loop), shifting gaze generates ocular-proprioception which can be used to update a movement (feedback-feedforward), or efference copy could be used to direct hand movements (feedforward). In this experiment we used a double-step task and manipulated the utility of ocular-proprioceptive feedback from eye to head position by removing the second target during the saccade. We confirm the advantage of free gaze for sequential movements with a double-step pointing task and document eye-hand lead times of approximately 200 ms for both initial movements and secondary movements. The observation that participants move gaze well ahead of the current hand target dismisses foveal feedback as a major contribution. We argue for a feedforward model based on eye movement efference as the major factor in enabling accurate hand movements. The results with the double-step target task also suggest the need for some buffering of efference and ocular-proprioceptive signals to cope with the situation where the eye has moved to a location ahead of the current target for the hand movement. We estimate that this buffer period may range between 120 and 200 ms without significant impact on hand movement accuracy.

Cognitive behaviour therapy for psychosis: current evidence and future directions

The past decade has seen considerable growth in the evidence base of cognitive behavioural therapy for psychosis. Consistent reports of moderate effect sizes have led to such interventions being recommended as part of routine clinical practice. Most of this evidence is based on a generic form of CBT for psychosis applied to a heterogeneous group. An increase in the effectiveness of cognitive behavioural interventions may require new protocols. Such therapeutic developments should be based on the theoretical understanding of the psychological processes associated with specific forms of psychotic presentation. The current evidence base of CBT for psychosis is reviewed, and barriers that have held back the development of this research are discussed.

Cognitive therapy for anxiety disorders: current status and future directions.

This paper reviews recent theoretical, conceptual and practice developments in cognitive-behaviour therapy (CBT) for anxiety disorders. The empirical status of CBT for anxiety disorders is reviewed and recent advances in the field are outlined. Challenges for the future development of CBT for the anxiety disorders are examined in relation to the efficacy, effectiveness and cost-effectiveness of the approach. It is concluded that the major challenge currently facing CBT for anxiety disorders in the UK is how to meet the increased demand for provision whilst maintaining high levels of efficacy and effectiveness. It is suggested that the creation of an evidence base for the dissemination of CBT needs to become a priority for empirical investigation in order effectively to expand the provision of CBT for anxiety disorders.

Evolving features-algorithms knowledge map to support NIDS data intelligence and learning loop architecting – a generalised approach to NIDS pattern feature space knowledge processing

This paper describes a proposed new approach to the Computer Network Security Intrusion Detection Systems (NIDS) application domain knowledge processing focused on a topic map technology-enabled representation of features of the threat pattern space as well as the knowledge of situated efficacy of alternative candidate algorithms for pattern recognition within the NIDS domain. Thus an integrative knowledge representation framework for virtualisation, data intelligence and learning loop architecting in the NIDS domain is described together with specific aspects of its deployment.

Optimising the feedback loop of a millimetre-wave absolute photoacoustic power meter using H-infinity control synthesis

An H-infinity control strategy has been developed for the design of controllers used in feedback controlled electrical substitution measurements (FCESM). The methodology has the potential to provide substantial improvements in both response time and resolution of a millimetre-wave absolute photoacoustic power meter.

Historical and current machine intelligence

In this article, we provide an initial insight into the study of MI and what it means for a machine to be intelligent. We discuss how MI has progressed to date and consider future scenarios in a realistic and logical way as much as possible. To do this, we unravel one of the major stumbling blocks to the study of MI, which is the field that has become widely known as "artificial intelligence"

Intestinal microflora of human infants and current trends for its nutritional modulation

Diet, among other environmental and genetic factors, is currently recognised to have an important role in health and disease. There is increasing evidence that the human colonic microbiota can contribute positively towards host nutrition and health. As such, dietary modulation has been proposed as important for improved gut health, especially during the highly sensitive stage of infancy. Differences in gut microflora composition and incidence of infection occur between breast- and formula-fed infants. Human milk components that cannot be duplicated in infant formulae could possibly account for these differences. However, various functional food ingredients such as oligosaccharides, prebiotics, proteins and probiotics could effect a beneficial modification in the composition and activities of gut microflora of infants. The aim of the present review is to describe existing knowledge on the composition and metabolic activities of the gastrointestinal microflora of human infants and discuss various possibilities and opportunities for its nutritional modulation.

Dietary prebiotics: current status and new definition

In November 2008, a group of scientists met at the 6th Meeting of the International Scientific Association of Probiotics and Prebiotics (ISAPP) in London, Ontario, Canada, to discuss the functionality of prebiotics. As a result of this, it was concluded that the prebiotic field is currently dominated by gastrointestinal events. However, in the future, it may be the case that other mixed microbial ecosystems may be modulated by a prebiotic approach, such as the oral cavity, skin and the urogenital tract. Therefore, a decision was taken to build upon the current prebiotic status and define a niche for ‘dietary prebiotics’. This review is co-authored by the working group of ISAPP scientists and sets the background for defining a dietary prebiotic as ‘‘a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health’’.

An overview of the current status of research into adopting high levels of renewables in Ireland

This paper provides an overview of the reduction targets that Ireland has set in the context of decarbonising their electricity generation through the use of renewables. The main challenges associated with integrating high levels (>20% of installed capacity) of non-dispatchable renewable generation are identified. The rising complexity of the challenge as renewable penetration levels increase is highlighted. A list of relevant research questions is then proposed, and an overview is given into the previous work that has gone into answering some of them. In particular, studies into the Irish energy market are identified, the current knowledge gap is described, and areas of necessary future research are suggested

Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs

Data on the potential health benefits of dietary flavanols and procyanidins, especially in the context of cardiovascular health, are considerable and continue to accumulate. Significant progress has been made in flavanol analytics and the creation of phytonutrient-content food databases, and novel data emanated from epidemiological investigations as well as dietary intervention studies. However, a comprehensive understanding of the pharmacological properties of flavanols and procyanidins, including their precise mechanisms of action in vivo, and a conclusive, consensus-based accreditation of a causal relationship between intake and health benefits in the context of primary and secondary cardiovascular disease prevention is still outstanding. Thus, the objective of this review is to identify and discuss key questions and gaps that will need to be addressed in order to conclusively demonstrate whether or not dietary flavanols and procyanidins have a role in preventing, delaying the onset of, or treating cardiovascular diseases, and thus improving human life expectancy and quality of life.

A novel scheme for human-friendly and time-delays robust neuropredictive teleoperation

A novel Neuropredictive Teleoperation (NPT) Scheme is presented. The design results from two key ideas: the exploitation of the measured or estimated neural input to the human arm or its electromyograph (EMG) as the system input and the employment of a predictor of the arm movement, based on this neural signal and an arm model, to compensate for time delays in the system. Although a multitude of such models, as well as measuring devices for the neural signals and the EMG, have been proposed, current telemanipulator research has only been considering highly simplified arm models. In the present design, the bilateral constraint that the master and slave are simultaneously compliant to each other's state (equal positions and forces) is abandoned, thus obtaining a simple to analyzesuccession of only locally controlled modules, and a robustness to time delays of up to 500 ms. The proposed designs were inspired by well established physiological evidence that the brain, rather than controlling the movement on-line, programs the arm with an action plan of a complete movement, which is then executed largely in open loop, regulated only by local reflex loops. As a model of the human arm the well-established Stark model is employed, whose mathematical representation is modified to make it suitable for an engineering application. The proposed scheme is however valid for any arm model. BIBO-stability and passivity results for a variety of local control laws are reported. Simulation results and comparisons with traditional designs also highlight the advantages of the proposed design.