Effect of a tumour-produced lipid-mobilizing factor on protein synthesis and degradation

Treatment of murine myoblasts, myotubes and tumour cells with a tumour-produced lipid mobilizing factor (LMF), caused a concentration-dependent stimulation of protein synthesis, within a 24 h period. There was no effect on cell number or [3H] thymidine incorporation, but a similar concentration-dependent stimulation of 2-deoxyglucose uptake. LMF produced an increase in intracellular cyclic AMP levels, which was linearly (r2 = 0.973) related to the increase in protein synthesis. The effect of LMF was attenuated by the adenylate cyclase inhibitor MDL12330A, and was additive with the stimulation produced by forskolin. Both propranolol (10 μM) and the specific β3-adrenergic receptor antagonist SR 59230A (10-5M), significantly reduced the stimulation of protein synthesis induced by LMF. Protein synthesis was also increased by 69% (P = 0.006) in soleus muscles of mice administered LMF, while there was a 26% decrease in protein degradation (P = 0.03). While LMF had no effect on the lysosomal enzymes, cathepsins B and L, there was a decrease in proteasome activity, as determined both by the 'chymotrypsin-like' enzyme activity, as well as expression of proteasome α-type subunits, determined by Western blotting. These results show that in addition to its lipid-mobilizing activity LMF also increases protein accumulation in skeletal muscle both by an increase in protein synthesis and a decrease in protein catabolism. © 2001 Cancer Research Campaign.

Leisure at work in Britain, West Germany, France and Japan : a cross-cultural comparative study

The aim of this thesis was to investigate the impact of changing values and attitudes toward work and the workplace in Britain, West Germany, France and Japan. A cross-national approach was adopted in order to gain a better understanding of differences and similarities in behaviour and to identify aspects specific to each society. Although the relationship between work and leisure has been thoroughly examined and there is a growing body of literature on changes in the values associated with these two phenomena, little research has been carried out into leisure at work. Studies of work time have tended to consider it as a homogeneous block, whereas recent research suggests that more attention should be devoted to unravelling the multiple uses of time at the workplace. The present study sought to review and analyse this new approach to the study of work time, and special attention is devoted to an examination of definitions of leisure, recreation, free time and work within the context of the workplace. The cross-cultural comparative approach gave rise to several problems due to the number of countries involved and the unusual combination of factors being investigated. The main difficulties were differences in the amount and quality of literature available, the non-comparability of existing data, definitions of concepts and socio-linguistic terms, and problems over access to organizations for fieldwork. Much of the literature generalizes about patterns of behaviour and few authors isolate factors specific to particular societies. In this thesis new empirical work is therefore used to ascertain the extent to which generalizations can be made from the literature and characteristics peculiar to each of the four countries identified. White-collar employees in large, broadly comparable companies were studied using identical questionnaires in the appropriate language. Respondents selected were men and women, aged between 20-65 years and either managers or non-managers. Patterns of leisure at work were found to be broadly similar in the national contexts, but with the Japanese and the West Germans experiencing the least leisure at work, and the British and the French perceiving the most. The general trend seems to be toward convergence of attitudes regarding leisure at work in the four countries. Explanations for variations in practice were sought within the wider societal contexts of each country.

A systems approach to public sector budgeting: the case of the planning, programming, budgeting system for the health and personal social services

The aim of this thesis is to examine the specific contextual factors affecting the applicability and development of the planning, programming, budgeting system (P.P.B.S.) as a systems approach to public sector budgeting. The concept of P.P.B.S. as a systems approach to public sector budgeting will first be developed and the preliminary hypothesis that general contextual factors may be classified under political, structural and cognitive headings will be put forward. This preliminary hypothesis will be developed and refined using American and early British experience. The refined hypothesis will then be tested in detail in the case of the English health and personal social services (H.P.S.S.), The reasons for this focus are that it is the most recent, the sole remaining, and the most significant example in British central government outside of defence, and is fairly representative of non-defence government programme areas. The method of data collection relies on the examination of unpublished and difficult to obtain central government, health and local authority documents, and interviews with senior civil servants and public officials. The conclusion will be that the political constraints on, or factors affecting P.P.B.S., vary with product characteristics and cultural imperatives on pluralistic decision-making; that structural constraints vary with the degree of coincidence of programme and organisation structure and with the degree of controllability of the organisation; and finally, that cognitive constraints vary according to product characteristics, organisational responsibilities, and analytical effort.

Knowledge-based systems and engineering software

The work described was carried out as part of a collaborative Alvey software engineering project (project number SE057). The project collaborators were the Inter-Disciplinary Higher Degrees Scheme of the University of Aston in Birmingham, BIS Applied Systems Ltd. (BIS) and the British Steel Corporation. The aim of the project was to investigate the potential application of knowledge-based systems (KBSs) to the design of commercial data processing (DP) systems. The work was primarily concerned with BIS's Structured Systems Design (SSD) methodology for DP systems development and how users of this methodology could be supported using KBS tools. The problems encountered by users of SSD are discussed and potential forms of computer-based support for inexpert designers are identified. The architecture for a support environment for SSD is proposed based on the integration of KBS and non-KBS tools for individual design tasks within SSD - The Intellipse system. The Intellipse system has two modes of operation - Advisor and Designer. The design, implementation and user-evaluation of Advisor are discussed. The results of a Designer feasibility study, the aim of which was to analyse major design tasks in SSD to assess their suitability for KBS support, are reported. The potential role of KBS tools in the domain of database design is discussed. The project involved extensive knowledge engineering sessions with expert DP systems designers. Some practical lessons in relation to KBS development are derived from this experience. The nature of the expertise possessed by expert designers is discussed. The need for operational KBSs to be built to the same standards as other commercial and industrial software is identified. A comparison between current KBS and conventional DP systems development is made. On the basis of this analysis, a structured development method for KBSs in proposed - the POLITE model. Some initial results of applying this method to KBS development are discussed. Several areas for further research and development are identified.

Gender differences in the relationships between bullying at school and unhealthy eating and shape-related attitudes and behaviours

Background. Previous research has found links between being a victim of bullying and reporting more unhealthy eating behaviours and cognitions, particularly in girls. However, little is known about the factors that might mediate these relationships. Aim. The present study compared the relationships between bullying, emotional adjustment, restrained eating, and body dissatisfaction in adolescent boys and girls. Sample/method. Self-report data were collected from a sample of 11- to 14-year-olds (N= 376) on experiences of bullying, emotional symptoms, and unhealthy eating and shape-related attitudes and behaviours. Results. Bullying, emotional symptoms, restrained eating, and body dissatisfaction were all correlated. Emotional symptoms were found to significantly mediate the relationships between verbal bullying with body dissatisfaction in girls but not in boys. Conclusions. Findings suggest that the experience of being verbally bullied places adolescent girls at risk of developing emotional problems which can then lead to body dissatisfaction. Longitudinal research is necessary to disentangle these pathways in more detail to facilitate the development of informed interventions to support children who are being bullied.

Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • 6-Mercaptopurine (6-MP) and azathioprine (AZA) are both inactive prodrugs that require intracellular activation into the active 6-thioguanine nucleotides (6-TGNs). • This metabolic process undergoes three different competitive pathways that are catalysed by three different enzymes; xanthine oxidase (XO), thiopurine methyltransferase (TPMT) and inosine triphosphatase (ITPA), all of which exhibit genetic polymorphisms. • Although the impact of genetic variation in the TPMT gene on treatment outcome and toxicity has been demonstrated, the role of other polymorphisms remains less well known. WHAT THIS STUDY ADDS • New information on the allelic variation of these three enzymes (XO, TPMT and ITPA) and their influence on 6-MP/AZA metabolism and toxicity. • Confirmation of the association of TPMT polymorphism with haematological toxicity. • Identified potential genetic characteristics that may contribute to higher risk of adverse events (such as ITPA IVS2+21A→C mutation). AIMS - To examine the allelic variation of three enzymes involved in 6-mercaptopurine/azathioprine (6-MP/AZA) metabolism and evaluate the influence of these polymorphisms on toxicity, haematological parameters and metabolite levels in patients with acute lymphoblastic leukaemia (ALL) or inflammatory bowel disease (IBD). METHODS - Clinical data and blood samples were collected from 19 ALL paediatric patients and 35 IBD patients who were receiving 6-MP/AZA therapy. All patients were screened for seven genetic polymorphisms in three enzymes involved in mercaptopurine metabolism [xanthine oxidase, inosine triphosphatase (C94→A and IVS2+21A→C) and thiopurine methyltransferase]. Erythrocyte and plasma metabolite concentrations were also determined. The associations between the various genotypes and myelotoxicity, haematological parameters and metabolite concentrations were determined. RESULTS - Thiopurine methyltransferase variant alleles were associated with a preferential metabolism away from 6-methylmercaptopurine nucleotides (P = 0.008 in ALL patients, P = 0.038 in IBD patients) favouring 6-thioguanine nucleotides (6-TGNs) (P = 0.021 in ALL patients). Interestingly, carriers of inosine triphosphatase IVS2+21A→C variants among ALL and IBD patients had significantly higher concentrations of the active cytotoxic metabolites, 6-TGNs (P = 0.008 in ALL patients, P = 0.047 in IBD patients). The study confirmed the association of thiopurine methyltransferase heterozygosity with leucopenia and neutropenia in ALL patients and reported a significant association between inosine triphosphatase IVS2+21A→C variants with thrombocytopenia (P = 0.012). CONCLUSIONS - Pharmacogenetic polymorphisms in the 6-MP pathway may help identify patients at risk for associated toxicities and may serve as a guide for dose individualization.

Investigating the influence of African American and African Caribbean race on primary care doctors' decision making about depression

This paper explores differences in how primary care doctors process the clinical presentation of depression by African American and African-Caribbean patients compared with white patients in the US and the UK. The aim is to gain a better understanding of possible pathways by which racial disparities arise in depression care. One hundred and eight doctors described their thought processes after viewing video recorded simulated patients presenting with identical symptoms strongly suggestive of depression. These descriptions were analysed using the CliniClass system, which captures information about micro-components of clinical decision making and permits a systematic, structured and detailed analysis of how doctors arrive at diagnostic, intervention and management decisions. Video recordings of actors portraying black (both African American and African-Caribbean) and white (both White American and White British) male and female patients (aged 55 years and 75 years) were presented to doctors randomly selected from the Massachusetts Medical Society list and from Surrey/South West London and West Midlands National Health Service lists, stratified by country (US v.UK), gender, and years of clinical experience (less v. very experienced). Findings demonstrated little evidence of bias affecting doctors' decision making processes, with the exception of less attention being paid to the potential outcomes associated with different treatment options for African American compared with White American patients in the US. Instead, findings suggest greater clinical uncertainty in diagnosing depression amongst black compared with white patients, particularly in the UK. This was evident in more potential diagnoses. There was also a tendency for doctors in both countries to focus more on black patients' physical rather than psychological symptoms and to identify endocrine problems, most often diabetes, as a presenting complaint for them. This suggests that doctors in both countries have a less well developed mental model of depression for black compared with white patients. © 2014 The Authors.

Placebo expectancy effects in the relationship between glucose and cognition

The present study investigated the extent of expectancy in the ability of glucose to affect cognitive performance. Using a within-subjects design, subjects (n 26) completed four experimental sessions (in counterbalanced order and after an initial practice session) during which they were given a 500 ml drink 30 min prior to completing a cognitive assessment battery. In addition, all subjects completed a baseline practice session during which they were given no drink. During two of the sessions, subjects were given a drink containing 50 g glucose and on the other two they were given a drink containing aspartame. A balanced placebo design was used, such that for half the sessions subjects were accurately informed as to the content of the drink (glucose or aspartame), whereas in the other two sessions they were misinformed as to the content of the drink. The task battery comprised a 6 min visual analogue of the Bakan vigilance task, an immediate verbal free-recall task, an immediate verbal recognition memory task and a measure of motor speed (two-finger tapping). Blood glucose and self-reported mood were also recorded at several time points during each session. Glucose administration was found to improve recognition memory times, in direct contrast to previous findings in the literature. Glucose administration also improved performance on the Bakan task (relative to the control drink), but only in sessions where subjects were informed that they would receive glucose and not when they were told that they would receive aspartame. There were no effects either of the nature of the drink or expectancy on the other measures. These results are interpreted in terms of there being some contribution of expectancy concerning the positive effects of glucose on cognition in studies which have not used an equi-sweet dose of aspartame as a control drink.

History and symptom taking in contact lens fitting and aftercare

Aim: To appraise history and symptom taking for contact lens consultations, to determine current practice and to make recommendations for best practice. Method: The peer reviewed academic literature was reviewed and the results informed a survey completed by 256 eye care practitioners (ECPs) on their current practice and influences. Results: The last eye-test date, last contact lens aftercare (for existing wearers) and reason for visit are key questions for most ECPs. Detailed use of contact lens questions are more commonly applied in aftercares than when refitting patients who have previously discontinued wear (87% vs 56% use), whereas questions on ocular and general history, medication and lifestyle were generally more commonly utilised for new patients than in aftercares (72% vs 50%). 75% of ECPs requested patients bring a list of their medication to appointments. Differential diagnosis questioning was thorough in most ECPs (87% of relevant questions asked). Attempts to optimise compliance included oral instruction (95% always) and written patient instructions (95% at least sometimes). Abbreviations were used by 39% of respondents (26% used ones provided by a professional body). Conclusion: There is scope for more consistency in history and symptom taking for contact lens consultations and recommendations are made.

LETs and NESTs:voices, views and vignettes

This book is a collection of essays written by teachers and academics working and researching in contexts where Native English-Speaking Teachers (NESTs) are employed and work on a daily basis with Local English Teachers (LETs).

"Quality lives on":quality initiatives and practices in Australia and Britain

Purpose-The purpose of this research is to explore the incidence of innovative approaches to quality in both Australia and Britain, the reasons behind their implementation, the ways in which they were undertaken and the success factors and the pitfalls encountered along the way. Design/methodology/ approach-A structured postal questionnaire was sent to 1,000 quality managers in both Australia and Britain. A response was received from 129 Australian and 175 British companies, who reported on why they did or did not introduce a new quality initiative within the past five years. Findings-A comparative analysis shows trends, similarities and differences, and future directions of quality in both countries. The paper concludes by identifying important lessons for senior management needing to make changes in this important aspect of any business. A high proportion of organisations in both countries are actively undertaking new quality initiatives. The impetus to change and the barriers to successful implementation were common to both countries. The type of initiative differed between the two countries, with a preponderance of ISO 9000 in Australia amongst a much wider choice of approaches than in Britain. There is a low take-up of Six Sigma in both countries, particularly in Australia. Originality/value-The paper offers a recent insight into quality approaches undertaken in both countries and identifies important lessons for senior management. © 2010 Emerald Group Publishing Limited. All rights reserved.

Le prix de l'individualité. Maine de Brian, Samuel Taylor Coleridge et la volonté: Deux postétités distinctes

This thesis is concerned with Maine de Biran’s and Samuel Taylor Coleridge’s conceptions of will, and the way in which both thinkers’ posterities have been affected by the central role of these very conceptions in their respective bodies of thought. The research question that animates this work can therefore be divided into two main parts, one of which deals with will, while the other deals with its effects on posterity. In the first pages of the Introduction, I make the case for a comparison between two philosophers, and show how this comparison can bring one closer to truth, understood not in objective, but in subjective terms. I then justify my choice by underlining that, in spite of their many differences, Maine de Biran and Samuel Taylor Coleridge followed comparable paths, intellectually and spiritually, and came to similar conclusions concerning the essential activity of the human mind. Finally, I ask whether it is possible that this very focus on the human will may have contributed to the state of both thinkers’ works and of the reception of those works. This prologue is followed by five parts. In the first part, the similarities and differences between the two thinkers are explored further. In the second part, the connections between philosophy and singularity are examined, in order to show the ambivalence of the will as a foundation for truth. The third part is dedicated to the traditional division between subject and object in psychology, and its relevance in history and in moral philosophy. The fourth part tackles the complexity of the question of influence, with respect to both Maine de Biran’s and Coleridge’s cases, both thinkers being indebted to many philosophers of all times and places, and having to rely heavily on others for the publication, or the interpretation of their own works. The fifth part is concerned with the different aspects of the faculty of will, and primarily its relationship with interiority, as incommensurability, and actual, conditioned existence in a certain historical and spatial context. It ends with a return to the question of will and posterity and an announcement of what will be covered in the main body of the thesis. The main body is divided into three parts:‘L’émancipation’, ‘L’affirmation, and ‘La projection’. The first part is devoted to the way Maine de Biran and Samuel Taylor Coleridge extricated themselves from one epistemological paradigm to contribute to the foundation of another. It is divided in four chapters. The first chapter deals with the aforementioned change of paradigm, as corresponding to the emergence of two separate but associated movements, Romanticism and what the French philosopher refers to as ‘The Age of History’. The second chapter concerns the movement that preceded them, i.e. the Enlightenment, its main features according to both of our thinkers, and the two epistemological models that prevailed under it and influenced them heavily in their early years: Sensationism (Maine de Biran) and Associationism (Coleridge). The third chapter is about the probable influence of Immanuel Kant and his followers on Maine de Biran and Coleridge, and the various facts that allow us to claim originality for both thinkers’ works. In the fourth chapter, I contrast Maine de Biran and Coleridge with other movements and thinkers of their time, showing that, contrary to their respective thoughts, Maine de Biran and Coleridge could not but break free from the then prevailing systematic approach to truth. The second part of the thesis is concerned with the first part of its research question, namely, Maine de Biran’s and Coleridge’s conceptions of the will. It is divided into four chapters. The first chapter is a reflection on the will as a paradox: on the one hand, the will cannot be caused by any other phenomenon, or it is no longer a will; but it cannot be left purely undetermined, as if it is, it is then not different from chance. It thus needs, in order to be, to be contradictorily already moral. The second chapter is a comparison between Maine de Biran’s and Coleridge’s accounts of the origin of the will, where it is found that the French philosopher only observes that he has a will, whereas the English philosopher postulates the existence of this will. The comparison between Maine de Biran’s and Coleridge’s conceptions of the will is pursued in the third chapter, which tackles the question of the coincidence between the will and the self, in both thinkers’ works. It ends with the fourth chapter, which deals with the question of the relationship between the will and what is other to it, i.e. bodily sensations, passions and desires. The third part of the thesis focuses on the second part of its research question, namely the posterity of Maine de Biran’s and Coleridge’s works. It is divided into four chapters. The first chapter constitutes a continuation of the last chapter of the preceding part, in that that it deals with Maine de Biran’s and Coleridge’s relations to the ‘other’, and particularly their potential and actual audience, and with the way these relations may have affected their writing and publishing practices. The second chapter is a survey of both thinkers’ general reception, where it is found that, while Maine de Biran has been claimed by two important movements of thoughts as their initiator, Coleridge has been neglected by the only real movement he could have, or may indeed have pioneered. The third chapter is more directly concerned with the posterities of Maine de Biran’s and Coleridge’s conceptions of will, and attempts to show that the approach to, and the meaning of the will have evolved throughout the nineteenth century, and in the French Spiritualist and the British Idealist movements, from an essentially personal one to a more impersonal one. The fourth chapter is a partial conclusion, whose aim is to give a precise idea of where Maine de Biran and Coleridge stand, in relation to their century and to the philosophical movements and matters we are concerned with. The conclusion is a recapitulation of what has been found, with a particular emphasis on the dialogue initiated between Maine de Biran and Coleridge on the will, and the relation between will and posterity. It suggests that both thinkers have to pay the price of a problematic reception for the individuality that pervades their respective works, and goes further in suggesting that s/he who chooses to found his individuality on the will is bound to feel this incompleteness in his/her own personal life more acutely than s/he who does not. It ends with a reflection on fixedness and movement, as the two antagonistic states that the theoretician of the will paradoxically aspires to.

User interface design support for the development of knowledge-based systems

The present scarcity of operational knowledge-based systems (KBS) has been attributed, in part, to an inadequate consideration shown to user interface design during development. From a human factors perspective the problem has stemmed from an overall lack of user-centred design principles. Consequently the integration of human factors principles and techniques is seen as a necessary and important precursor to ensuring the implementation of KBS which are useful to, and usable by, the end-users for whom they are intended. Focussing upon KBS work taking place within commercial and industrial environments, this research set out to assess both the extent to which human factors support was presently being utilised within development, and the future path for human factors integration. The assessment consisted of interviews conducted with a number of commercial and industrial organisations involved in KBS development; and a set of three detailed case studies of individual KBS projects. Two of the studies were carried out within a collaborative Alvey project, involving the Interdisciplinary Higher Degrees Scheme (IHD) at the University of Aston in Birmingham, BIS Applied Systems Ltd (BIS), and the British Steel Corporation. This project, which had provided the initial basis and funding for the research, was concerned with the application of KBS to the design of commercial data processing (DP) systems. The third study stemmed from involvement on a KBS project being carried out by the Technology Division of the Trustees Saving Bank Group plc. The preliminary research highlighted poor human factors integration. In particular, there was a lack of early consideration of end-user requirements definition and user-centred evaluation. Instead concentration was given to the construction of the knowledge base and prototype evaluation with the expert(s). In response to this identified problem, a set of methods was developed that was aimed at encouraging developers to consider user interface requirements early on in a project. These methods were then applied in the two further projects, and their uptake within the overall development process was monitored. Experience from the two studies demonstrated that early consideration of user interface requirements was both feasible, and instructive for guiding future development work. In particular, it was shown a user interface prototype could be used as a basis for capturing requirements at the functional (task) level, and at the interface dialogue level. Extrapolating from this experience, a KBS life-cycle model is proposed which incorporates user interface design (and within that, user evaluation) as a largely parallel, rather than subsequent, activity to knowledge base construction. Further to this, there is a discussion of several key elements which can be seen as inhibiting the integration of human factors within KBS development. These elements stem from characteristics of present KBS development practice; from constraints within the commercial and industrial development environments; and from the state of existing human factors support.

The control of technological change in the motor industry:a case study

This thesis is based upon a case study of the introduction of automated production technologies at the Longbridge plant of British Leyland in the period 1978 to 1980.The investment in automation was part of an overall programme of modernization to manufacture the new 'Mini Metro' model. In the first Section of the thesis, the different theoretical perspectives on technological change are discussed. Particular emphasis is placed upon the social role of management as the primary controllers of technological change. Their actions are seen to be oriented towards the overall strategy of the firm, integrating the firm's competitive strategy with production methods and techniques.This analysis is grounded in an examination of British Leyland's strategies during the 1970s.. The greater part of the thesis deals with the efforts made by management to secure their strategic objectives in the process of technological change against the conflicting claims of their work-force. Examination of these efforts is linked to the development of industrial relations conflict at Longbridge and in British Leyland as a whole.Emphasis is placed upon the struggle between management in pursuit of their version of efficiency and the trade unions in defence of job controls and demarcations. The thesis concludes that the process of technological change in the motor industry is controlled by social forces,with the introduction of new technologies being closely intertwined with management!s political relations with the trade unions.

Triggering trust : to what extent does the question influence the answer when evaluating the perceived importance of trust triggers?

Trust is a critical component of business to consumer (B2C) e-Commerce success. In the absence of typical environmental cues that consumers use to assess vendor trustworthiness in the offline retail context, online consumers often rely on trust triggers embedded within e-Commerce websites to contribute to the establishment of sufficient trust to make an online purchase. This paper presents and discusses the results of a study which took an initial look at the extent to which the context or manner in which trust triggers are evaluated may exert influence on the importance attributed to individual triggers.