Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis:an observational, cross-sectional study

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. Trial registration: ISRCTN Registry identifier: ISRCTN93945409. Registered 2 December 2011.

Zwei Wege zur 'Aufhellung der Finsternisse in der Welt'. Zum untergründigen Wechselverhältnis von Literatur & Malerei bei Thomas Bernhard & Francis Bacon:for subterranean exchange relationship between literature and painting in Thomas Bernhard & Francis Bacon

This chapter undertakes the first examination of the role the fine arts play in Thomas Bernhard’s prose works. Though not as prominent as the role of music, painting and the fine arts play a crucial role in Frost and Alte Meister; these two novels coincidentally also happen to be the first and last novels written by Bernhard. This chapter takes its cue from the positive role awarded to Francis Bacon in the novel Das Kalkwerk. Comparing and contrasting the relation and influence between the art of Bacon and the literature of Bernhard, I am able to demonstrate a number of surprising analogies. Following a brief biographical synopsis, I focus on four aesthetic operations that are crucial to both artists. Using the key terms of ‘middle way’, ‘variation’, ‘vibration’ and ‘mediation’, I am able to uncover surprising similarities between the novels and the paintings. These hidden connections are further confirmed by looking at the two artists’ shared major motifs, namely the slaughterhouse, the scream, the relation between animals and humans, and pain. This bleak outlook on the state of human civilisation that these two major artists of the end of the 20th century share, embodies both a warning and a prophesy for the 21st century.

Investigating the process of translation:humour translation norms, strategies and approaches in children's literature

Research in the present thesis is focused on the norms, strategies,and approaches which translators employ when translating humour in Children's Literature from English into Greek. It is based on process-oriented descriptive translation studies, since the focus is on investigating the process of translation. Viewing translation as a cognitive process and a problem soling activity, this thesis Think-aloud protocols (TAPs) in order to investigate translator's minds. As it is not possible to directly observe the human mind at work, an attempt is made to ask the translators themselves to reveal their mental processes in real time by verbalising their thoughts while carrying out a translation task involving humour. In this study, thirty participants at three different levels of expertise in translation competence, i.e. tn beginner, ten competent, and ten experts translators, were requested to translate two humourous extracts from the fictional diary novel The Secret Diary of Adrian Mole, Aged 13 ¾ by Sue Townsend (1982) from English into Greek. As they translated, they were asked to verbalise their thoughts and reason them, whenever possible, so that their strategies and approaches could be detected, and that subsequently, the norms that govern these strategies and approaches could be revealed. The thesis consists of four parts: the introduction, the literature review, the study, and the conclusion, and is developed in eleven chapters. the introduction contextualises the study within translation studies (TS) and presents its rationale, research questions, aims, and significance. Chapters 1 to 7 present an extensive and inclusive literature review identifying the principles axioms that guide and inform the study. In these seven chapters the following areas are critically introduced: Children's literature (Chapter 1), Children's Literature Translation (Chapter 2), Norms in Children's Literature (Chapter 3), Strategies in Children's Literature (Chapter 4), Humour in Children's Literature Translation (Chapter 5), Development of Translation Competence (Chapter 6), and Translation Process Research (Chapter 7). In Chapters 8 - 11 the fieldwork is described in detail. the piolot and the man study are described with a reference to he environments and setting, the participants, the research -observer, the data and its analysis, and limitations of the study. The findings of the study are presented and analysed in Chapter 9. Three models are then suggested for systematising translators' norms, strategies, and approaches, thus, filling the existing gap in the field. Pedagogical norms (e.g. appropriateness/correctness, famililarity, simplicity, comprehensibility, and toning down), literary norms (e.g. sound of language and fluency). and source-text norms (e.g. equivalence) were revealed to b the most prominent general and specific norms governing the translators'  strategies and approaches in the process of translating humour in ChL. The data also revealed that monitoring and communication strategies (e.g. additions, omissions, and exoticism) were the prevalent strategies employed by translators. In Chapter 10 the main findings and outcomes of a potential secondary benefit (beneficial outcomes) are discussed on the basis of the research questions and aims of the study, and implications of the study are tackled in Chapter 11. In the conclusion, suggestions for future directions are given and final remarks noted.

Location and network effects on innovation success:evidence for UK, German and Irish manufacturing plants

Recent developments in the new economic geography and the literature on regional innovation systems have emphasised the potentially important role of networking and the characteristics of firms' local operating environment in shaping their innovative activity. Modeling UK, German and Irish plants' investments in R&D, technology transfer and networking, and their effect on the extent and success of plants' innovation activities, casts some doubt on the importance of both of these relationships. In particular, our analysis provides no support for the contention that firms or plants in the UK, Ireland or Germany with more strongly developed external links (collaborative networks or technology transfer) develop greater innovation intensity. However, although inter-firm links also have no effect on the commercial success of plants' innovation activity, intra-group links are important in terms of achieving commercial success. We also find evidence that R&D, technology transfer and networking inputs are substitutes rather than complements in the innovation process, and that there are systematic sectoral and regional influences in the efficiency with which such inputs are translated into innovation outputs. © 2001 Elsevier Science B.V.

Interviewing adult witnesses and victims

In this chapter, we discuss the interviewing of adult witnesses and victims with reference to how the extant psychological and linguistic literature has contributed to understanding and informing interview practice over the past 20 years and how it continues to support practical and procedural improvements. We have only scratched the surface of this important and complex topic, but throughout this chapter we have directed readers to many in-depth reviews and some of the most contemporary research literature currently available in this domain. We have introduced the PEACE model and described the Cognitive Interview procedure and its development. We have also discussed rapport building, question types and communication style, all with reference to witness memory and practical interviewing. Finally, we highlight areas that would benefit from research, for example conducting interviews with interpreters, and how new training initiatives are seeking to improve interview procedures and interviewer practice.

Exploring civil servant resistance to M-government:a story of transition and opportunities in Turkey

The concept of mobility, related to technology in particular, has evolved dramatically over the last two decades including: (i) hardware ranging from walkmans to Ipods, laptops to netbooks, PDAs to 3G mobile phone; (ii) software supporting multiple audio and video formats driven by ubiquitous mobile wireless access, WiMax, automations such as radio frequency ID tracking and location aware services. Against the background of increasing budget deficit, along with the imperative for efficiency gains, leveraging ICT and mobility promises for work related tasks, in a public administration context, in emerging markets, point to multiple possible paths. M-government transition involve both technological changes and adoption to deliver government services differently (e.g. 24/7, error free, anywhere to the same standards) but also the design of digital strategies including possibly competing m-government models, the re-shaping of cultural practices, the creation of m-policies and legislations, the structuring of m-services architecture, and progress regarding m-governance. While many emerging countries are already offering e-government services and are gearing-up for further m-government activities, little is actually known about the resistance that is encountered, as a reflection of civil servants' current standing, before any further macro-strategies are deployed. Drawing on the resistance and mobility literature, this chapter investigates how civil servants' behaviors, in an emerging country technological environment, through their everyday practice, react and resist the influence of m-government transition. The findings points to four main type of resistance namely: i) functional resistance; ii) ideological resistance; iii) market driven resistance and iv) geographical resistance. Policy implication are discussed in the specific context of emerging markets. © 2011, IGI Global.

Stakeholder accounting : the case of the electricity industry in England and Wales

This thesis proposes to explore the potential for stakeholder based accounting as a means to explain the social performance of organisations. It argues that organisations have a contract with society and as a consequence they must be accountable to that society for their actions. Further, it is suggested that as part of this accountability there is a broader need in the public interest for social accounting. Due to the pluralistic nature of modern societies it is argued that a stakeholder framework is one way in which this accountability can be achieved. In order to consider the nature of such social accounting a case study of the electricity industry in England and Wales is undertaken. This industry is very important to modern society, has significant environment implications and has a recent history of remarkable change. These factors make it an interesting and unique case within which to consider accountability. From the performance measurement and accounting literature and a series of interviews with both stakeholders and privatised companies a model of stakeholder performance is developed. This is then used to analyse the electricity industry in England and Wales since privatisation. The objective is to demonstrate how certain stakeholders have fared, whether they have won or lost. Further, institutional and resource dependency theories are used to consider what factors determine the relative success or failure of the different stakeholder groups. Finally the possible implications of recent developments in Social Accounting Standards, such as the Global Reporting Initiative (GRI), AccountAbility 1000 (AA1000) and Social Accountability 8000 (SA8000), and the potential for Internet reporting are considered.

Work stressors, strains and hospital unit performance

Hospital employees who work in an environment with zero tolerance to error, face several stressors that may result in psychological, physiological, and behavioural strains, and subsequently, in suboptimal performance. This thesis includes two studies which investigate the stressor-to-strain-to-performance relationships in hospitals. The first study is a cross-sectional, multi-group investigation based on secondary data from 65,142 respondents in 172 acute/specialist UK NHS trusts. This model proposes that senior management leadership predicts social support and job design which, in turn, moderate stressors-to-strains across team structure. The results confirm the model's robustness. Regression analysis provides support for main effects and minimal support for moderation hypotheses. Therefore, based on its conclusions and inherent limitations, study one lays the framework for study two. The second study is a cross-sectional, multilevel investigation of the strain-reducing effects of social environment on externally-rated unit-level performance based on primary data from 1,137 employees in 136 units, in a hospital in Malta. The term "social environment" refers to the prediction of the moderator variables, which is to say, social support and decision latitude/control, by transformational leadership and team climate across hospital units. This study demonstrates that transformational leadership is positively associated with social support, whereas team climate is positively associated with both moderators. At the same time, it identifies a number of moderating effects which social support and decision latitude/control, both separately and together, had on specific stressor-to-strain relationships. The results show significant mediated stressor-to-strain-to-performance relationships. Furthermore, at the higher level, unit-level performance is positively associated with shared unit-level team climate and with unit-level vision, the latter being one of the five sub-dimension of transformational leadership. At the same time, performance is also positively related to both transformational leadership and team climate when the two constructs are tested together. Few studies have linked the buffering effects of the social environment in occupational stress with performance. Therefore, this research strives to make a significant contribution to the occupational stress and performance literature with a focus on hospital practice. Indeed, the study highlights the wide-ranging and far-reaching implications that these findings provide for theory, management, and practice.

Antecedents and consequences of market orientation : an examination in the joint ventures' relational context

Market oriented behaviours have been found to be important predictors of business success across a wide array of studies. Despite their potential importance, research into market oriented behaviours in the joint venture (JV) context is very scarce. This study represents a novel attempt to address this gap by examining a set of antecedent factors which arises from sources outside a traditional firm’s boundary. An extensive review and synthesis of the market orientation and JV literature yielded a set of context-specific antecedent factors relevant to the JV’s relational context. In accordance with the perspective offered by the transaction cost theory, a system of hypotheses about the effects of these antecedent factors on JV’s market oriented behaviours was developed. In order to test these hypotheses, empirical evidence was collected by means of a mail survey to international joint ventures operating in the coastal regions of mainland China. A sample of 191 JV firms was collected as a result. Following well established procedures for scale development and purification as recommended in the methodology literature, the scales were critically trimmed and reviewed for their psychometric properties. The conceptual model was tested with a structural equation model. Results suggested that a number of context-specific antecedents are in fact important determinants of JVs’ level of market oriented behaviours. In addition, the linkage between market oriented behaviours and market performance was also successfully established.

Pre-conception care : current practice and methods of provision

This thesis examines the present provisions for pre-conception care and the views of the providers of services. Pre-conception care is seen by some clinicians and health educators as a means of making any necessary changes in life style, corrections to imbalances in the nutritional status of the prospective mother (and father) and the assessment of any medical problems, thus maximizing the likelihood of the normal development of the baby. Pre-conception care may be described as a service to bridge the gap between the family planning clinic and the first ante-natal booking appointment. There were three separate foci for the empirical research - the Foresight organisation (a charity which has pioneered pre-conception care in Britain); the pre-conception care clinic at the West London Hospital, Hammersmith; and the West Midlands Regional Health Authority. The six main sources of data were: twenty five clinicians operating Foresight pre-conception clinics, couples attending pre-conception clinics, committee members of the Foresight organisation, staff of the West London Hospital pre-conception clinic, Hammersmith, District Health Education Officers working in the West Midlands Regional Health Authority and the members of the Ante-Natal Care Action Group, a sub-group of the Regional Health Advisory Group on Health Promotion and Preventive Medicine. A range of research methods were adopted. These were as follows: questionnaires and report forms used in co-operation with the Foresight clinicians, interviews, participant observation discussions and informal meetings and, finally, literature and official documentation. The research findings illustrated that pre-conception care services provided at the predominantly private Foresight clinics were of a rather `ad hoc' nature. The type of provision varied considerably and clearly reflected the views held by its providers. The protocol which had been developed to assist in the standardization of results was not followed by the clinicians. The pre-conception service provided at the West London Hospital shared some similarities in its approach with the Foresight provision; a major difference was that it did not advocate the use of routine hair trace metal analysis. Interviews with District Health Education Officers and with members of the Ante Natal Care Action Group revealed a tentative and cautious approach to pre-conception care generally and to the Foresight approach in particular. The thesis concludes with a consideration of the future of pre-conception care and the prospects for the establishment of a comprehensive pre-conception care service.

Ownership concentration:'Private benefits of control' and debt financing

Building on the ‘law and economics’ literature, this paper analyses corporate governance implications of debt financing in an environment where a dominant owner is able to extract ex ante ‘private benefits of control’. Ownership concentration may result in lower efficiency, measured as a ratio of a firm’s debt to investment, and this effect depends on the identity of the largest shareholder. Moreover, entrenched dominant shareholder(s) may be colluding with fixed-claim holders in extracting ‘control premium’. One of possible outcomes is a ‘crowding out’ of entrepreneurial firms from the debt market, and this is supported by evidence from the transition economies.

Changing employment relation systems in Japan:cases of the Mitsubishi Chemical Group and the Federation of Shinkin Banks

Over the past decade or so a number of changes have been observed in traditional Japanese employment relations (ERs) systems such as an increase in non-regular workers, a move towards performance-based systems and a continuous decline in union membership. There is a large body of Anglo-Saxon and Japanese literature providing evidence that national factors such as national institutions, national culture, and the business and economic environment have significantly influenced what were hitherto three ‘sacred’ aspects of Japanese ERs systems (ERSs). However, no research has been undertaken until now at the firm level regarding the extent to which changes in national factors influence ERSs across firms. This article develops a model to examine the impact of national factors on ER systems; and analyses the impact of national factors at the firm level ER systems. Based on information collected from two different groups of companies, namely Mitsubishi Chemical Group (MCG) and Federation of Shinkin Bank (FSB) the research finds that except for a few similarities, the impact of national factors is different on Japanese ER systems at the firm level. This indicates that the impact of national factors varies in the implementation of employment relations factors. In the case of MCG, national culture has less to do with seniority-based system. Study also reveals that the national culture factors have also less influence on an enterprise-based system in the case of FSB. This analysis is useful for domestic and international organizations as it helps to better understand the role of national factors in determining Japanese ERSs.

Post-translational modifications and mass spectrometry detection

In this review, we provide a comprehensive bibliographic overview of the role of mass spectrometry and the recent technical developments in the detection of post-translational modifications (PTMs). We briefly describe the principles of mass spectrometry for detecting PTMs and the protein and peptide enrichment strategies for PTM analysis, including phosphorylation, acetylation and oxidation. This review presents a bibliographic overview of the scientific achievements and the recent technical development in the detection of PTMs is provided. In order to ascertain the state of the art in mass spectrometry and proteomics methodologies for the study of PTMs, we analyzed all the PTM data introduced in the Universal Protein Resource (UniProt) and the literature published in the last three years. The evolution of curated data in UniProt for proteins annotated as being post-translationally modified is also analyzed. Additionally, we have undertaken a careful analysis of the research articles published in the years 2010 to 2012 reporting the detection of PTMs in biological samples by mass spectrometry. © 2013 Elsevier Inc.

The role of working memory in compulsive checking and OCD:a systematic classification of 58 experimental findings

Despite the large body of research regarding the role of memory in OCD, the results are described as mixed at best (Hermans et al., 2008). For example, inconsistent findings have been reported with respect to basic capacity, intact verbal, and generally affected visuospatial memory. We suggest that this is due to the traditional pursuit of OCD memory impairment as one of the general capacity and/or domain specificity (visuospatial vs. verbal). In contrast, we conclude from our experiments (i.e., Harkin & Kessler, 2009, 2011; Harkin, Rutherford, & Kessler, 2011) and recent literature (e.g., Greisberg & McKay, 2003) that OCD memory impairment is secondary to executive dysfunction, and more specifically we identify three common factors (EBL: Executive-functioning efficiency, Binding complexity, and memory Load) that we generalize to 58 experimental findings from 46 OCD memory studies. As a result we explain otherwise inconsistent research – e.g., intact vs. deficient verbal memory – that are difficult to reconcile within a capacity or domain specific perspective. We conclude by discussing the relationship between our account and others', which in most cases is complementary rather than contradictory.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.