Biomarkers

Introduction – Why do we need ‘biomarkers? Biomarkers of protein oxidation Introduction Major issues/questions Protein carbonyl biomarkers Biochemistry Methods of measurement Storage, stability and limitations in use Protein thiol biomarkers Biochemistry Methods of measurement Storage, stability and limitations on use Aliphatic amino acid biomarkers Biochemistry Methods of measurement Storage, stability and limitations on use Oxidised Tryptophan Biomarkers Biochemistry Method of measurement Storage, stability and limitations on use Oxidised tyrosine biomarkers Biochemistry Methods of measurement Storage, stability and limitations on use Formation of neoepitopes on oxidised proteins Validation of assays for protein oxidation biomarkers Relationship of protein oxidation to disease Modulation of protein oxidation biomarkers by antioxidants Future perspectives Introduction to lipid peroxidation biomarkers Introduction: biochemistry of lipid peroxidation Malondialdehyde Methods of measurement Storage, stability and limitations on use Conjugated dienes Method of measurement Storage, stability and limitations of use LDL lag phase Method of measurement Storage, stability and limitations of use Hydrocarbon gases Biochemistry Method of measurement Storage, stability and limitations on use Lipofuscin Biochemistry Method of measurement Storage, stability and limitation on use Lipid peroxides Biochemistry Method of measurement Storage, stability and limitations on use Isoprostanes Biochemistry Method of measurement Storage, stability and limitations on use Possible new biomarkers of lipid oxidation Relationship of lipid peroxidation to disease Modulation of lipid peroxidation biomarkers by antioxidants Functional consequences of lipid peroxidation Contribution of dietary intake to lipid peroxidation products Biomarkers of DNA oxidation Introduction Confounding factors Units and terminology Nuclear and mitochondrial DNA damage Lymphocytes as surrogate tissues Measurement of DNA damage with the comet assay Practical details Storage, stability, and limitations of the assay Measurement of DNA base oxidation by HPLC Practical details Storage, stability and limitations of the method Measurement of DNA base oxidation by GC–MS Biochemistry of 8-oxoguanine, adenine and fapy derivatives Methods of measurement Storage, stability and limitations of the method Analysis of guanine oxidation products in urine Method of measurement Limitations and criticisms Immunochemical methods Methods of measurement Storage, stability, and limitations of the assay 32P post-labelling Method of measurement Limitations and criticisms Validation of assays for DNA oxidation Oxo-dGuo in lymphocyte DNA Urinary measurements DNA–aldehyde adducts Biochemistry Method of measurement Products of reactive nitrogen species Endpoints arising from oxidative DNA damage Mutations Chromosome aberrations Micronuclei Site-specific DNA damage Relationship of DNA oxidation to disease Modulation of DNA oxidation biomarkers by antioxidants Direct and indirect effects of oxidative stress: measures of total oxidant/antioxidant levels Visualisation of cellular oxidants Biochemistry: histochemical detection of ROS Method of measurement Limitations, storage and stability Measurement of hydrogen peroxide Biochemistry Methods of measurement Storage, stability and limitations on use Measurement of the ratio of antioxidant/oxidised antioxidant Biochemistry Method of measurement Storage, stability and limitations on use Total antioxidant capacity Biochemistry Terminology Methods of measurement Storage, stability and limitations on use Validation of assays for direct oxidant and antioxidant biomarkers Relationship of oxidant/antioxidant measurement to disease Modulation of oxidant/antioxidant biomarkers by dietary antioxidants Induction of genes in response to oxidative stress Background Measurement of antioxidant responsive genes and proteins Effects of antioxidant intake on the activity of antioxidant enzymes

Objective grading of the anterior eye

Purpose. To convert objective image analysis of anterior ocular surfaces into recognisable clinical grades, in order to provide a more sensitive and reliable equivalent to current subjective grading methods; a prospective, randomized study correlating clinical grading with digital image assessment. Methods. The possible range of clinical presentations Of bulbar and palpebral hyperaemia, palpebral roughness and corneal staining were represented by 4 sets of 10 images. The images were displayed in random order and graded by 50 clinicians using both subjective CCLRU and Efron grading scales. Previously validated objective image analysis was performed 3 times oil each of the 40 images. Digital measures included edge-detection and relative-coloration components. Step-wise regression analysis determined correlations between the average subjective grade and the objective image analysis measures. Results. Average subjective grades Could be predicted by a combination of the objective image analysis components. These digital ``grades'' accounted for between 69%, (for Efron scale-graded palpebral redness) and 98% (for Efron scale-graded bulbar hyperaemia) of the subjective variance. Conclusions. The results indicate that clinicians may use a combination of vessel areas and overall hue in their judgment of clinical severity for certain conditions. Objective grading call take these aspects into account, and be used to predict an average ``objective grade'' to be used by a clinician in describing the anterior eye. These measures are more sensitive and reliable than subjective grading while still utilizing familiar terminology, and can be applied in research or practice to improve the detection, and monitoring of ocular surface changes.

Strategy-as-practice:a review and future directions for the field

This review maps and critically evaluates the rapidly growing body of research in the strategy-as-practice field. Following an introduction on the emergence and foundations of strategy-as-practice, the review is structured in three main parts, based on the terminology, issues and research agendas outlined in the field. First, the paper examines the concepts of practitioners and praxis. A typology of nine possible domains for strategy-as-practice research is developed, based on the way that different studies conceptualize the strategy practitioner and the level of strategy praxis that they aim to explain. Second, the paper reviews the concept of practices, which has been adopted widely but inconsistently within the strategy-as-practice literature. While there is no dominant view on practices, the review maps the various concepts of practices that inform the strategy-as-practice field and outlines avenues for future research. The final section attends to the call for strategy-as-practice research to develop and substantiate outcomes that may better explain or inform strategy praxis. Five categories of outcomes are found within existing empirical studies, and an agenda for building upon this evidence is advanced. The paper concludes with a summation of the current state of the field and some recommendations on how to take strategy-aspractice research forward.

Creating demand for better health by using social marketing techniques

The most significant environmental change to support people who want to give up smoking is the legislation to ban smoking in public places. Following Scotland in March 2006, and Wales and Northern Ireland in April 2007, England moves one step closer to being smoke free on 1 July 2007, when it becomes illegal to smoke in almost every enclosed public place and workplace. Social marketing will be used to support this health promoting policy and will become more prominent in the design of health promotion campaigns of the future. Social marketing is not a new approach to promoting health but its adoption by the Government does represent a paradigm shift in the challenge to change public opinion and social norms. As a result some behaviours, like smoking or excessive alcohol consumption, will no longer be socially acceptable. The Department of Health has decided that social marketing should be used in England to guide all future health promotion efforts directed at achieving behavioural goals. This paradigm shift was announced in Chapter 2 of the “Choosing health” White Paper with its emphasis on the consumer, noting that a wide range of lifestyle choices are marketed to people, although health as a commodity itself has not been marketed. The DoH has an internal social marketing development unit to integrate social marketing principles into its work and ensure that providers deliver. The National Centre for Social Marketing has funding to provide ongoing support, to build capacity and capability in the workforce. This article describes the distinguishing features of the social marketing approach. It seeks to answer some questions. Is this really a new idea, a paradigm shift, or simply a change in terminology? What do the marketing principles offer that is new, or are they merely familiar ideas repackaged in marketing jargon? Will these principles be more effective than current health promotion practice and, if so, how does it work? Finally, what are the implications for community pharmacy?

A dictionary of globalization

Globalization has become one of the most important topics within politics and economics. This new title explains some of the related terminology, summarizes the surrounding theories and examines the international organizations involved. With the proliferation of communications and the rise of the multi-national corporation, the concept of globalization is vitally important to the modern political environment. The structure of the modern economy, based on information production and diffusion, has made national boundaries largely irrelevant. A Dictionary of Globalization explains theories, philosophies and ideologies, and includes short biographies of leading activists, theorists and thinkers such as Noam Chomsky, Karl Marx and José Bové. Concepts, issues and terms key to the understanding of globalization also have clear and concise definitions, including democracy, civil society, non-governmental organizations and ethnicity. Cross-referenced for ease of use, this title aims to be of great benefit to anyone studying politics or sociology. It will prove essential to public and academic libraries, as well as to businesses, government departments, embassies and journalists.

The classical theory of field evaporation

The field evaporation literature has been carefully analysed and is shown to contain various confusions. After redefining consistent terminology, this thesis investigates the mechanisms of field evaporation, in particular, the relevance of the theoretical mechanisms by analysing the available experimental data. A new formalism `extended image-hump formalism' is developed and is used to devise several tests of whether the image-hump mechanism is operating. The general conclusion is that in most cases the Mueller mechanism is not operating and escape takes place via Gomer-type mechanisms.

Statnote 10: the two-way analysis of variance

The two-way design has been variously described as a matched-sample F-test, a simple within-subjects ANOVA, a one-way within-groups ANOVA, a simple correlated-groups ANOVA, and a one-factor repeated measures design! This confusion of terminology is likely to lead to problems in correctly identifying this analysis within commercially available software. The essential feature of the design is that each treatment is allocated by randomization to one experimental unit within each group or block. The block may be a plot of land, a single occasion in which the experiment was performed, or a human subject. The ‘blocking’ is designed to remove an aspect of the error variation and increase the ‘power’ of the experiment. If there is no significant source of variation associated with the ‘blocking’ then there is a disadvantage to the two-way design because there is a reduction in the DF of the error term compared with a fully randomised design thus reducing the ‘power’ of the analysis.

Comparative performance of analytical techniques for polyhexamethylene biguanide (PHMB) in ophthalmic solutions

Purpose: The use of PHMB as a disinfectant in contact lens multipurpose solutions has been at the centre of much debate in recent times, particularly in relation to the issue of solution induced corneal staining. Clinical studies have been carried out which suggest different effects with individual contact lens materials used in combination with specific PHMB containing care regimes. There does not appear to be, however, a reliable analytical technique that would detect and quantify with any degree of accuracy the specific levels of PHMB that are taken up and released from individual solutions by the various contact lens materials. Methods: PHMB is a mixture of positively charged polymer units of varying molecular weight that has maximum absorbance wavelength of 236 nm. On the basis of these properties a range of assays including capillary electrophoresis, HPLC, a nickelnioxime colorimetric technique, mass spectrophotometry, UV spectroscopy and ion chromatography were assessed paying particular attention to each of their constraints and detection levels. Particular interest was focused on the relative advantage of contactless conductivity compared to UV and mass spectrometry detection in capillary electrophoresis (CE). This study provides an overview of the comparative performance of these techniques. Results: The UV absorbance of PHMB solutions, ranging from 0.0625 to 50 ppm was measured at 236 nm. Within this range the calibration curve appears to be linear however, absorption values below 1 ppm (0.0001%) were extremely difficult to reproduce. The concentration of PHMB in solutions is in the range of 0.0002–0.00005% and our investigations suggest that levels of PHMB below 0.0001% (levels encountered in uptake and release studies) can not be accurately estimated, in particular when analysing complex lens care solutions which can contain competitively absorbing, and thus interfering, species in the solution. The use of separative methodologies, such as CE using UV detection alone is similarly limited. Alternative techniques including contactless conductivity detection offer greater discrimination in complex solutions together with the opportunity for dual channel detection. Preliminary results achieved by TraceDec1 contactless conductivity detection, (Gain 150%, Offset 150) in conjunction with the Agilent capillary electrophoresis system using a bare fused silica capillary (extended light path, 50 mid, total length 64.5 cm, effective length 56 cm) and a cationic buffer at pH 3.2, exhibit great potential with reproducible PHMB split peaks. Conclusions: PHMB-based solutions are commonly associated with the potential to invoke corneal staining in combination with certain contact lens materials. However this terminology ‘PHMBbased solution’ is used primarily because PHMB itself has yet to be adequately implicated as the causative agent of the staining and compromised corneal cell integrity. The lack of well characterised adequately sensitive assays, coupled with the range of additional components that characterise individual care solutions pose a major barrier to the investigation of PHMB interactions in the lenswearing eye.

The management of stress amongst professional carers within a social services department

This thesis considers four broad areas:(i) ANALYSIS OF THE STRESS FIELD.(a) research studies, relevant to the British Social Services considering the cultural setting, and the rigor with which they were conducted; (b) models of stress, specifically examining the theoretical soundness and practical application of the Medical, Engineering and Transactional models;(c) organisational models of stress relating specifically to human service organisations.(ii) QUALITATIVE AND QUANTITATIVE RESEARCH METHODOLOGIES.(a) the appropriate application of each respective methodology and the particular usefulness of qualitative research designs; (b) the relevance of understanding the language and terminology associated with the subject area prior to the implementation of survey methods; (iii) FIELDWORK.(a) Phase 1. By use of focus groups, in-depth interviews and diary keeping amongst a small range of teams and managers, the Researcher develops a basic conceptual framework of stress within a Social Services context. In addition a small scale personality inventory was administered to participants.(b) Phase 2. This consisted of three key elements: 6 case studies in which the Researcher implements and appraises the impact of a range of intervention strategies designed to assist teams and their managers in dealing more effectively with stress; the administration of a large scale survey to all the field social work teams within the Social Services Department; an analysis of the user role within the stress process by way of two focus groups.(iv) THEORETICAL DEVELOPMENT.

Supporting English language teachers doing further degrees at a distance:a web based strategy researched

This thesis explores how the world-wide-web can be used to support English language teachers doing further studies at a distance. The future of education worldwide is moving towards a requirement that we, as teacher educators, use the latest web technology not as a gambit, but as a viable tool to improve learning. By examining the literature on knowledge, teacher education and web training, a model of teacher knowledge development, along with statements of advice for web developers based upon the model are developed. Next, the applicability and viability of both the model and statements of advice are examined by developing a teacher support site (bttp://www. philseflsupport. com) according to these principles. The data collected from one focus group of users from sixteen different countries, all studying on the same distance Masters programme, is then analysed in depth. The outcomes from the research are threefold: A functioning website that is averaging around 15, 000 hits a month provides a professional contribution. An expanded model of teacher knowledge development that is based upon five theoretical principles that reflect the ever-expanding cyclical nature of teacher learning provides an academic contribution. A series of six statements of advice for developers of teacher support sites. These statements are grounded in the theoretical principles behind the model of teacher knowledge development and incorporate nine keys to effective web facilitation. Taken together, they provide a forward-looking contribution to the praxis of web supported teacher education, and thus to the potential dissemination of the research presented here. The research has succeeded in reducing the proliferation of terminology in teacher knowledge into a succinct model of teacher knowledge development. The model may now be used to further our understanding of how teachers learn and develop as other research builds upon the individual study here. NB: Appendix 4 is only available only available for consultation at Aston University Library with prior arrangement.

The making of an ideology of the third way:the evolution of christian democracy in Germany (with special reference to 1945-49)

This study investigates the search for the third way in the history of German Christian Democracy. Today, in the United Kingdom, the 'third way' is seen as a new phenomenon, a synthesis of post-war belief in the welfare state and neo-liberal conservatism. Yet it insufficiently acknowledges that the origins of third way thinking, the marriage of social justice with free market economics, of individualism with collective responsibility, are found in the early philosophies of Catholic Social Theory and Protestant Social Ethical Teaching in Germany. This study shows that in the hundred years from the 1840s to the end of the 1940s, there were Catholic and Protestant socio-ethical thinkers and political reformists in Germany who attempted to bridge the philosophical differences between liberalism and socialism, to develop a socio-economic order based on Christian moral values. It will focus on the period 1945-1949, when the CDU was founded as the first interdenominational, Christian party. The study provides the first comprehensive account of the political debates in Christian democratic groups in the Soviet, British, French and American allied occupied zones, also giving equal attention to the contribution from the Protestant wing, alongside the more widely acknowledged role of Catholics in the birth of the CDU. It examines how Christian Democrats envisaged correcting the aberrations of German history, by uniting all social classes and Christian religions in one all-embracing Volkspartei, and transforming party politics from its earlier obsession with sectarian and ideological interests towards a more pragmatic 'third way' programme. The study argues that through the making of its ideology, the CDU modified the nation's understanding of its history, re-interpreted its traditions, and redefined the meaning and perception of established political philosophies. This reveals how the ambiguity of political terminology, and the flexible practice of 'third way' politics, were an invaluable political resource in the CDU's campaign for unity, ideological legitimisation and political power.

Reacting and responding in TESOL Quarterly:a generic analysis of procedure and purpose in intertextual critical exchanges

A key feature of ‘TESOL Quarterly’, a leading journal in the world of TESOL/applied linguistics, is its ‘Forum’ section which invites ‘responses and rebuttals’ from readers to any of its articles. These ‘responses or rebuttals’ form the focus of this research. In the interchanges between readers reacting to earlier research articles in TESOL Quarterly and authors responding to the said reaction I – examine the texts for evidence of genre-driven structure, whether shared between both ‘reaction’ and ‘response’ sections, or peculiar to each section, and attempt to determine the precise nature of the intended communicative purpose in particular and the implications for academic debate in general. The intended contribution of this thesis is to provide an analysis of how authors of research articles and their critics pursue their efforts beyond the research article which precipitated these exchanges in order to be recognized by their discourse community as, in the terminology of Swales (1981:51), ‘Primary Knowers’. Awareness of any principled generic process identified in this thesis may be of significance to practitioners in the applied linguistics community in their quest to establish academic reputation and in their pursuit of professional development. These findings may also be of use in triggering productive community discussion as a result of the questions they raise concerning the present nature of academic debate. Looking beyond the construction and status of the texts themselves, I inquire into the kind of ideational and social organization such exchanges keep in place and examine an alternative view of interaction. This study breaks new ground in two major ways. To the best of my knowledge, it is the first exploration of a bipartite, intertextual structure laying claim to genre status. Secondly, in its recourse to the comments of the writers’ themselves rather than relying exclusively on the evidence of their texts, as is the case with most studies of genre, this thesis offers an expanded opportunity to discuss perhaps the most interesting aspects of genre analysis – the light it throws on social ends and the role of genre in determining the nature of current academic debate as it here emerges.

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.

A dictionary of globalization

Globalization has become one of the most important topics within politics and economics. This new title explains some of the related terminology, summarizes the surrounding theories and examines the international organizations involved. With the proliferation of communications and the rise of the multi-national corporation, the concept of globalization is vitally important to the modern political environment. The structure of the modern economy, based on information production and diffusion, has made national boundaries largely irrelevant. A Dictionary of Globalization explains theories, philosophies and ideologies, and includes short biographies of leading activists, theorists and thinkers such as Noam Chomsky, Karl Marx and José Bové. Concepts, issues and terms key to the understanding of globalization also have clear and concise definitions, including democracy, civil society, non-governmental organizations and ethnicity. Cross-referenced for ease of use, this title aims to be of great benefit to anyone studying politics or sociology. It will prove essential to public and academic libraries, as well as to businesses, government departments, embassies and journalists.

Strategic planning as communicative process

This thesis looks at the construction of a strategic plan within a British university (Unico). After a change in leadership, the well-known strategic planning sequence was adopted to set directions according to Unico’s three Missions, followed by the development of respective goals and measures. The evolving strategic content coincided with the development of Unico’s strategic plan. I was able to follow Unico’s planning efforts over 10 months, from first planning meeting to completion of its strategic plan. The main data source provided non-participant observation (n = 25) and ten versions of Unico’s strategic plan. Additionally, seventy-six interviews were held with participants at various points. In order to examine the strategic plan’s construction, I reconceptualised strategic planning as a communicative process consisting of oral talk and written text. Through this interplay strategic planning activities come in to being. Such reconceptualisation provided a conceptual framework to study the in situ interactions without neglecting contextual characteristics embedding the communicative process. Strategic plans are currently seen as promoting inflexibility and reinforcing the institutional nature of formal strategic planning. Adopting dialogism, as advocated by Bakhtin and Ricoeur, this research provides novel insights into the dialogic of strategy talk and strategy text, such as a strategic plan. Findings illustrated that a strategic plan production cycle provided a meaning making platform for its participants. Through recurrently amending the plan, its content became increasingly specific while at the same time reflecting agreed terminology. This thesis offers an alternative view on strategic planning, elaborates on the strategy-as-practice perspective, focusing on the under-explored area of individuals’ interactions at the micro level, and elaborates on the dialogic of text and agency/conversation, distinguishing between talk and text.