Cyclotron production of short-lived radionuclides and labelled compounds for use in biomedical research and clinical diagnosis

The works submitted in this thesis cover the development of methods for the production in a cyclotron of a variety of radionuclides and their incorporation in radio-labelled compounds for use in biomedical research. In addition, papers are included which describe biomedical applications of such radio-tracers. My co-authorship of these publications reflects my interest in the design and execution of experiments in the realm of interdisciplinary research. The original contributions to science embodied in the publications submitted include examples of novel radiochemistry applied in the areas of cyclotron production of short half-life radionuclides and their radiochemical purification. In many cases the use of these radionuclides in biomedical research has added new information to the body of medical scientific Toiowledge. Novel radiolabelling strategies using very short half-life radionuclides are included. These have necessitated the development of rapid radio-organic syntheses, several of which have been achieved using automated microchemical engineering process plants of my design. I have also developed novel systems for the administration of radionuclies and radio-labelled compounds of pharmaceutical quality, widely acknowledged to be "World Firsts." My invention of the (^81)Kr(^m) radionuclide generator resulted in publications covering a wide range of medical applications. These are included with the thesis. The device is now produced in many countries around the world for use both in routine clinical diagnosis and in research, particularly in lung disease. More recently, I have created an automated bedside infuser of H(_2)(^15)O, which has revolutionised measurements of regional cerebral blood flow using the technique of Positron Emission Tomography for in vivo regional mapping of brain activity

Suboptimal reporting practices in biomedical research

Responsible research practices and fair reporting is an element of research integrity. Articles published in The Lancet illustrated the problem of waste during various stages of research encompassing design, conduct and reporting. Given that much of this waste is avoidable, there is a need to develop and implement remedies. Of these, accurate interpretation and presentation of results in published data is essential in order to avoid producing misleading studies and waste valuable resources. The concept of “spin” has been investigated in scientific communications, defined as a way of reporting, not necessarily intentional, “that fails to faithfully reflect the nature and range of findings and that could affect the impression that the results produce in readers”, i.e., a way to distort science reporting without actually lying. The overarching aim of this PhD project was to identify and document suboptimal reporting practices in published reports and to suggest preferred strategies to overcome these. Through the research work presented in this thesis, we explored three key topics: (1) suboptimal reporting practices, such as mis-representation and over-interpretation of study findings (also known as spin) and inadequate study design or methods, in diagnostic/prognostic biomarker studies and randomized trials; (2) a proposed strategy aimed at reducing spin by conducting a collaborative field trial at The BMJ publishing group (London, UK); and (3) other aspects of suboptimal reporting practices and challenges in publication and dissemination of biomedical research. Our work builds on a growing number of research publications on research misconduct and misbehaviours, commonly named “questionable research practices”

Theranostic approach for the protein corona of polysaccharide nanoparticles.

Polysaccharide nanoparticles are promising materials in the wide range of disciplines such as medicine, nutrition, food production, agriculture, material science and others. They excel- not only in their non-toxicity and biodegradability but also in their easy preparation. As well as inorganic particles, a protein corona (PC) around polysaccharide nanoparticles is formed in biofluids. Moreover, it has been considered that the overall response of the organism to nanoparticles presence depends on the PC. This review summarises scientific publications about the structural chemistry of polysaccharide nanoparticles and their impact on theranostic applications. Three strategies of implementation of the PC in theranostics have been discussed: I) Utilisation of the PC in therapy; II) How the composition of the PC is analysed for specific disease markers; III) How the formed PC can interact with the immune system and enhances the immunomodulation or immunoelimination. Thus, the findings from this review can contribute to improve the design of drug delivery systems. However, it is still necessary to elucidate the mechanisms of nano-bio interactions and discover new connections in nanoscale research

Developing the Professional Knowledge of Teachers of Technology and STEM in Secondary Schools

The sixteen works presented in the thesis derive from eleven years as a teacher of Science, Technology, Engineering and Mathematics (STEM) in different secondary high schools in England and in Wales, and as a researcher and teacher educator for twenty-seven years, as first an educator of physics teachers at the University of Wales, Swansea from September 1987 and then of technology and science teachers at The Open University beginning in April 1992. The selected publications provide a unique 33-year arc of development and an interconnected overview of the way that an understanding of the elements of professional knowledge for teachers can be investigated and the results then used in the creation and the on-going development of initial and in-service teacher education programmes. The sixteen publications’ contribution to the field and their resulting impact is demonstrated, for example, by their having been cited 479 times. Using and exploiting a range of evaluative research methods that can be described as Research and Development (R&D), this thesis considers publications which address the education of teachers in general, and Design and Technology teachers and STEM teachers in particular. The publications coalesce around three interconnected themes that address three critically important research questions: Theme 1. Teacher Professional Knowledge - Research Question 1 (RQ1): What are the elements of teacher professional knowledge and what is their inter-relationship? • Empirical research conducted, and the resulting development of a general model of teacher professional knowledge (publications 1 – 4). • Exploitation of the model as a ‘Graphical Tool’ through an international collaboration in the DEPTH Project (Developing Professional Thinking for Technology Teachers) (publications 5 and 6). Theme 2. Developing Teachers of Technology - Research Question 2 (RQ2): In what ways can the suggested elements of teacher professional knowledge support the development of teachers of Technology? • Empirical research on teaching and learning and teacher education in technology education. • Development of approaches and models in technology teacher education including open and distance learning techniques (publications 7 – 10). • Comparative classroom-based research providing international perspectives in teaching technology (publications 10 – 13). Theme 3. Developing Teachers of STEM - Research Question 3 (RQ3): In what ways can the suggested elements of teacher professional knowledge support the development of teachers of STEM? • Empirical studies and a critical analysis of the relationship between science and technology in the UK. • Development of strategies both in teaching and in school organisation that need to be addressed when helping teachers meet the challenge of teaching STEM in the secondary school (publications 14 – 16). Using a research and development (R&D) methodology to evaluate and build on courses to develop teacher professional knowledge and addressing the Research Questions, the key concepts that the thesis contributes to new knowledge are: RQ1: • The discovery, verification, and exploitation of a new way to conceptualise the common aspects of teacher professional knowledge across subject domains. • The development of a graphical tool to explore teacher professional knowledge, and the discovery that teachers can use it to investigate and share professional understandings in their own contexts, demonstrating its applicability across education regimes internationally. RQ2: • The development of new open and distance learning techniques for the professional development of Technology teachers through the use of new technologies. RQ3: • The exploration, and dissemination of in-school strategies that can be used to develop and support secondary teachers of STEM, wherever they are located, by enabling them to collaborate by ‘looking sideways’ at the work that is done by colleagues in the contributory STEM subjects; and ways in which those developments can be supported by school leaders

Innovation, skills and performance in the downturn: an analysis of the UK innovation survey 2011

The link between firms’ innovation performance and economic cycles, especially major downturns such as that of 2008-10, is a matter of great policy significance, but is relatively under-researched at least at the level of micro data on business behaviour. It is, for example, often argued that economies need to ‘innovate out of recessions’ since innovation is positively associated with improvements in productivity that then lead to growth and better employment (Nesta, 2009). The issues of how individual firms respond to downturns through their investment in innovation, and how this impacts on innovation outputs and ultimately business performance and growth during and after downturns, has been less studied because relevant data has not been readily available. The UK Innovation Survey (UKIS) 2011 now makes this possible. The UKIS 2011 with reference period 2008 to 2010 covers the downturn in economic activity generated by the global financial crash. The build-up of panels over the life of the UKIS also supports analysis of the longer-term interactions between innovation and the business cycle. This report analyses the last four waves of the surveys. Further, the latest survey includes questions on whether firms employ a specific set of skills, which adds materially to the ability to research the role of skills and human capital in innovation at the micro level

Examining green production and its role within the competitive strategy of manufacturers

Purpose: This paper reviews current literature and contributes a set of findings that capture the current state-of-the-art of the topic of green production. Design/methodology/approach: A literature review to capture, classify and summarize the main body of knowledge on green production and, translate this into a form that is readily accessible to researchers and practitioners in the more mainstream operations management community. Findings: The existing knowledge base is somewhat fragmented. This is a relatively unexplored topic within mainstream operations management research and one which could provide rich opportunities for further exploration. Originality/value: This paper sets out to review current literature, from a more conventional production operations perspective, and contributes a set of findings that capture the current state-of-the-art of this topic

Wissensstandsanalyse zum Verbraucher- und Ernährungsverhalten bei ökologischen Lebensmitteln mit Einbezug der Außer-Haus-Verpflegung

Die vorliegende Studie enthält einen umfassenden Überblick zur nationalen wie internationalen Verbraucherforschung für Öko-Lebensmittel. Insgesamt wurden 562 Publikationen basierend auf 338 wissenschaftlichen Studien aus dem Zeitraum Januar 2000 bis Juni 2011 zu den Themengebieten Determinanten des Verbraucherverhaltens, Verbrauchersegmentierung, Produkt-, Preis-, Kommunikations- und Distributionspolitik sowie Außer-Haus-Verzehr analysiert und hinsichtlich ihrer Datengrundlage und Methodik bewertet. Die Betrachtung der einschlägigen englisch- und deutschsprachigen Literatur lieferte Erkenntnisse zum Wissensstand über die Verbraucherforschung für Öko-Lebensmittel und ermöglichte die Identifizierung relevanter Forschungslücken für Deutschland, die richtungsweisend für die zukünftige Forschung ist. Insgesamt ergab sich eine hohe Publikationsdichte insbesondere in den letzten vier Jahren. Zu den zahlenmäßig am häufigsten behandelten Themengebieten gehören die Determinanten des Verbraucherverhaltens, die Produktpolitik sowie die Preispolitik. Dennoch sind auch hier viele gänzlich unbearbeitete Fragestellungen, bspw. zu den Geschmackspräferenzen unterschiedlicher Verbraucher-gruppen, zu umweltfreundlichen Verpackungen sowie zur Preiskenntnis und Preispsychologie des Konsumenten, zu finden. Darüber hinaus konnten innovative Aspekte der Trendforschung zum Thema Öko-Lebensmittel ausgemacht werden. Andere Themengebiete wie zum Beispiel Kommunikationspolitik und Außer-Haus-Verzehr sind bisher kaum untersucht. Die Status-Quo-Analyse wurde mit den Ergebnissen aus einer Online-Befragung und einem Experten-Workshop ergänzt, um die Relevanz der identifizierten Forschungslücken einzuschätzen und den Forschungsbedarf aus Praktiker- und Expertensicht zu ermitteln. Aus dieser umfassenden Analyse konnten konkret Empfehlungen für zukünftige Forschungsschwerpunkte in Deutschland abgeleitet werden

Development and Validation of a Rule-based Time Series Complexity Scoring Technique to Support Design of Adaptive Forecasting DSS

Evidence from forecasting research gives reason to believe that understanding time series complexity can enable design of adaptive forecasting decision support systems (FDSSs) to positively support forecasting behaviors and accuracy of outcomes. Yet, such FDSS design capabilities have not been formally explored because there exists no systematic approach to identifying series complexity. This study describes the development and validation of a rule-based complexity scoring technique (CST) that generates a complexity score for time series using 12 rules that rely on 14 features of series. The rule-based schema was developed on 74 series and validated on 52 holdback series using well-accepted forecasting methods as benchmarks. A supporting experimental validation was conducted with 14 participants who generated 336 structured judgmental forecasts for sets of series classified as simple or complex by the CST. Benchmark comparisons validated the CST by confirming, as hypothesized, that forecasting accuracy was lower for series scored by the technique as complex when compared to the accuracy of those scored as simple. The study concludes with a comprehensive framework for design of FDSS that can integrate the CST to adaptively support forecasters under varied conditions of series complexity. The framework is founded on the concepts of restrictiveness and guidance and offers specific recommendations on how these elements can be built in FDSS to support complexity