Mild cognitive decline. A position statement of the Cognitive Decline Group of the European Innovation Partnership for Active and Healthy Ageing (EIPAHA)

Introduction Mild cognitive impairment (MCI) is a term used to describe a level of decline in cognition which is seen as an intermediate stage between normal ageing and dementia, and which many consider to be a prodromal stage of neurodegeneration that may become dementia. That is, it is perceived as a high risk level of cognitive change. The increasing burden of dementia in our society, but also our increasing understanding of its risk factors and potential interventions, require diligent management of MCI in order to find strategies that produce effective prevention of dementia. Aim To update knowledge regarding mild cognitive impairment, and to bring together and appraise evidence about the main features of clinical interest: definitions, prevalence and stability, risk factors, screening, and management and intervention. Methods Literature review and consensus of expert opinion. Results and conclusion MCI describes a level of impairment in which deteriorating cognitive functions still allow for reasonable independent living, including some compensatory strategies. While there is evidence for some early risk factors, there is still a need to more precisely delineate and distinguish early manifestations of frank dementia from cognitive impairment that is less likely to progress to dementia, and furthermore to develop improved prospective evidence for positive response to intervention. An important limitation derives from the scarcity of studies that take MCI as an endpoint. Strategies for effective management suffer from the same limitation, since most studies have focused on dementia. Behavioural changes may represent the most cost-effective approach.

Lexical learning and dysgraphia in a group of adults with developmental dyslexia

We investigated the ability to learn new words in a group of 22 adults with developmental dyslexia/dysgraphia and the relationship between their learning and spelling problems. We identified a deficit that affected the ability to learn both spoken and written new words (lexical learning deficit). There were no comparable problems in learning other kinds of representations (lexical/semantic and visual) and the deficit could not be explained in terms of more traditional phonological deficits associated with dyslexia (phonological awareness, phonological STM). Written new word learning accounted for further variance in the severity of the dysgraphia after phonological abilities had been partialled out. We suggest that lexical learning may be an independent ability needed to create lexical/formal representations from a series of independent units. Theoretical and clinical implications are discussed. © 2005 Psychology Press Ltd.

The effect of ward design on the well-being of post-operative patients

Changes in the design of hospital wards have usually been determined by architects and members of the nursing and medical professions; the views and preferences of patients have seldom been sought directly. The Hospital Anxiety and Depression scale and the Disturbance Due to Hospital Noise questionnaire were administered to 64 female patients on bay and Nightingale wards together with a questionnaire designed for this study. Perceptions of social and physical factors of ward design were examined, and their relationship to psychological well-being and sleep patterns. The results show that the bay ward seemed to offer a more favourable environment for patients but some of the disadvantages of bay wards are balanced by better staffing levels and better and more modern facilities. Visibility to nurses was lower on the bay ward. The Nightingale ward was perceived as significantly noisier than the bay ward and noise levels were significantly correlated to anxiety scores. Paradoxically the increase in noise levels appeared to improve the perceived level of privacy on the Nightingale ward. Seventy-five per cent of patients were found to prefer the bay ward design, and since neither design appears to have major disadvantages their continued introduction should be encouraged. However, recommendations are made concerning the optimizing of patients' well-being within the bay ward setting.

A new phylogenetic group of Propionibacterium acnes

Immunofluorescence microscopy-based identification of presumptive Propionibacterium acnes isolates, using the P. acnes-specific mAb QUBPa3, revealed five organisms with an atypical cellular morphology. Unlike the coryneform morphology seen with P. acnes types I and II, these isolates exhibited long slender filaments (which formed large tangled aggregates) not previously described in P. acnes. No reaction with mAbs that label P. acnes types IA (QUBPa1) and II (QUBPa2) was observed. Nucleotide sequencing of the 16S rRNA gene (1484 bp) revealed the isolates to have between 99.8 and 99.9 % identity to the 16S rRNA gene of the P. acnes type IA, IB and II strains NCTC 737, KPA171202 and NCTC 10390, respectively. Analysis of the recA housekeeping gene (1047 bp) did reveal, however, a greater number of conserved nucleotide polymorphisms between the sequences from these isolates and those from NCTC 737 (98.9 % identity), KPA171202 (98.9 % identity) and NCTC 10390 (99.1 % identity). Phylogenetic investigations demonstrated that the isolates belong to a novel recA cluster or lineage distinct from P. acnes types I and II. We now propose this new grouping as P. acnes type III. The prevalence and clinical importance of this novel recA lineage amongst isolates of P. acnes remains to be determined.

Chronic administration of an aluminium-enriched diet impairs spatial orientation in a sub-group of C57BL6 female mice

Disturbances of spatial orientation are an early clinical component of senile dementia of the Alzheimer type (SDAT). since it has been suggested that an elevated aluminium intake associated with chronic nutritional deficiencies of calcium and magnesium may play an important role in the aetiology of SDAT, we have investigated the effect of such a dietary regime on the spatial orientation abilities of female C57BL6 mice using the Morris swimming pool test. Statistical analysis of the performances of control and experimental groups indicate that the ability to orientate towards a submerged and thus invisible platform is conistently and markedly impaired in the experimental group. The ability to orientate towards a visible platform is also significantly impaired although to a lesser extent. Analysis of the performances of individual animals demonstrate that this impairment of orientation in the experimental group only occurs in a sub-group of animals: the remainder display normal orientational ability.

Aspects of the design and control of manufacturing systems subject to demand uncertainty

The recent explosive growth in advanced manufacturing technology (AMT) and continued development of sophisticated information technologies (IT) is expected to have a profound effect on the way we design and operate manufacturing businesses. Furthermore, the escalating capital requirements associated with these developments have significantly increased the level of risk associated with initial design, ongoing development and operation. This dissertation has examined the integration of two key sub-elements of the Computer Integrated Manufacturing (CIM) system, namely the manufacturing facility and the production control system. This research has concentrated on the interactions between production control (MRP) and an AMT based production facility. The disappointing performance of such systems has been discussed in the context of a number of potential technological and performance incompatibilities between these two elements. It was argued that the design and selection of operating policies for both is the key to successful integration. Furthermore, policy decisions are shown to play an important role in matching the performance of the total system to the demands of the marketplace. It is demonstrated that a holistic approach to policy design must be adopted if successful integration is to be achieved. It is shown that the complexity of the issues resulting from such an approach required the formulation of a structured design methodology. Such a methodology was subsequently developed and discussed. This combined a first principles approach to the behaviour of system elements with the specification of a detailed holistic model for use in the policy design environment. The methodology aimed to make full use of the `low inertia' characteristics of AMT, whilst adopting a JIT configuration of MRP and re-coupling the total system to the market demands. This dissertation discussed the application of the methodology to an industrial case study and the subsequent design of operational policies. Consequently a novel approach to production control resulted. A central feature of which was a move toward reduced manual intervention in the MRP processing and scheduling logic with increased human involvement and motivation in the management of work-flow on the shopfloor. Experimental results indicated that significant performance advantages would result from the adoption of the recommended policy set.

Some aspects of system design for production management in the rolling-mill industry

Case studies in copper-alloy rolling mill companies showed that existing planning systems suffer from numerous shortcomings. Where computerised systems are in use, these tend to simply emulate older manual systems and still rely heavily on modification by experienced planners on the shopfloor. As the size and number of orders increase, the task of process planners, while seeking to optimise the manufacturing objectives and keep within the production constraints, becomes extremely complicated because of the number of options for mixing or splitting the orders into batches. This thesis develops a modular approach to computerisation of the production management and planning functions. The full functional specification of each module is discussed, together with practical problems associated with their phased implementation. By adapting the Distributed Bill of Material concept from Material Requirements Planning (MRP) philosophy, the production routes generated by the planning system are broken down to identify the rolling stages required. Then to optimise the use of material at each rolling stage, the system generates an optimal cutting pattern using a new algorithm that produces practical solutions to the cutting stock problem. It is shown that the proposed system can be accommodated on a micro-computer, which brings it into the reach of typical companies in the copper-alloy rolling industry, where profit margins are traditionally low and the cost of widespread use of mainframe computers would be prohibitive.

Aspects of the design and operation of production control systems in manufacturing industry

Computerised production control developments have concentrated on Manufacturing Resources Planning (MRP II) systems. The literature suggests however, that despite the massive investment in hardware, software and management education, successful implementation of such systems in manufacturing industries has proved difficult. This thesis reviews the development of production planning and control systems, in particular, investigates the causes of failures in implementing MRP/MRP II systems in industrial environments and argues that the centralised and top-down planning structure, as well as the routine operational methodology of such systems, is inherently prone to failure. The thesis reviews the control benefits of cellular manufacturing systems but concludes that in more dynamic manufacturing environments, techniques such as Kanban are inappropriate. The basic shortcomings of MRP II systems are highlighted and a new enhanced operational methodology based on distributed planning and control principles is introduced. Distributed Manufacturing Resources Planning (DMRP), was developed as a capacity sensitive production planning and control solution for cellular manufacturing environments. The system utilises cell based, independently operated MRP II systems, integrated into a plant-wide control system through a Local Area Network. The potential benefits of adopting the system in industrial environments is discussed and the results of computer simulation experiments to compare the performance of the DMRP system against the conventional MRP II systems presented. DMRP methodology is shown to offer significant potential advantages which include ease of implementation, cost effectiveness, capacity sensitivity, shorter manufacturing lead times, lower working in progress levels and improved customer service.

Local and systemic delivery of a novel group of inhibitors of transglutaminase enzyme: A potential approach for treating of catheter-related complications and liver fibrosis

The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis.

The role of industrial design in technological innovation

This is an exploratory study in a field which previously was virtually unexplored. The aim is to identify, for the benefit of innovators, the influence of industrial design on the commercial success of new science-based products used for professional and industrial purposes. The study is a contribution to the theory of success and failure in industrial innovation. The study begins by defining the terminology. To place the investigation in context, there is then a review of past attempts by official policy-making bodies to improve the competitiveness of British products of manufacture through good design. To elucidate the meaning of good design, attempts to establish a coherent philosophy of style in British products of manufacture during the same period are also reviewed. Following these reviews, empirical evidence is presented to identify what actually takes place in successful firms when industrial design is allocated a role in the process of technological innovation. The evidence comprises seven case studies of new science-based products used for professional or industrial purposes which have received Design Council Awards. To facilitate an objective appraisal, evidence was obtained by conducting separate semi-structured interviews, the detail of which is described, with senior personnel in innovating firms, with industrial design consultants, and with professional users. The study suggests that the likelihood of commercial success in technological innovation is greater when the form, configuration, and the overall appearance of a new product, together with the detail which delineates them, are consciously and expertly controlled. Moreover, uncertainty in innovation is likely to be reduced if the appearance of a new product is consciously designed to facilitate recognition and comprehension. Industrial design is an especially significant factor when a firm innovates against a background of international competition and comparable levels of technological competence in rival firms. The likelihood of success in innovation is enhanced if design is allocated a role closely identified with the total needs of the user and discrete from the engineering function in company organisation. Recent government measures, initiated since this study began, are corroborative of the findings.

The implementation of a design of experiments strategy to increase recombinant protein yields in yeast (review)

Biological processes are subject to the influence of numerous factors and their interactions, which may be non-linear in nature. In a recombinant protein production experiment, understanding the relative importance of these factors, and their influence on the yield and quality of the recombinant protein being produced, is an essential part of its optimisation. In many cases, implementing a design of experiments (DoE) approach has delivered this understanding. This chapter aims to provide the reader with useful pointers in applying a DoE strategy to improve the yields of recombinant yeast cultures.