• E-banking operational risk assessment. A soft computing approach in the context of the Nigerian banking industry.

      Cullen, Andrea J.; Neagu, Daniel; Ochuko, Rita E. (University of BradfordSchool of Computing, Informatics and Media, 2013-12-02)
      This study investigates E-banking Operational Risk Assessment (ORA) to enable the development of a new ORA framework and methodology. The general view is that E-banking systems have modified some of the traditional banking risks, particularly Operational Risk (OR) as suggested by the Basel Committee on Banking Supervision in 2003. In addition, recent E-banking financial losses together with risk management principles and standards raise the need for an effective ORA methodology and framework in the context of E-banking. Moreover, evaluation tools and / or methods for ORA are highly subjective, are still in their infant stages, and have not yet reached a consensus. Therefore, it is essential to develop valid and reliable methods for effective ORA and evaluations. The main contribution of this thesis is to apply Fuzzy Inference System (FIS) and Tree Augmented Naïve Bayes (TAN) classifier as standard tools for identifying OR, and measuring OR exposure level. In addition, a new ORA methodology is proposed which consists of four major steps: a risk model, assessment approach, analysis approach and a risk assessment process. Further, a new ORA framework and measurement metrics are proposed with six factors: frequency of triggering event, effectiveness of avoidance barriers, frequency of undesirable operational state, effectiveness of recovery barriers before the risk outcome, approximate cost for Undesirable Operational State (UOS) occurrence, and severity of the risk outcome. The study results were reported based on surveys conducted with Nigerian senior banking officers and banking customers. The study revealed that the framework and assessment tools gave good predictions for risk learning and inference in such systems. Thus, results obtained can be considered promising and useful for both E-banking system adopters and future researchers in this area.
    • Early environments and neurobehavioural programming: Therapeutic actions of antidepressants. Neurobehavioural programming during development.

      Smythe, James W.; Fraser, Josie; Alrumaih, Ali M.S. (University of BradfordDepartment of pharmacy, 2014-05-07)
      Following decades of research on stress and its impact on behaviour, it is now widely accepted that selective psycho-pathologies, in particular clinical depression are more prevalent in humans with prior history of life-stress events. Interest in stress has led to questions about how it might affect the physiology and behaviour of animals exposed indirectly during gestational development. Not unexpectedly gestational stress has been shown to affect the offspring in several ways: endocrine responses to stress are elevated, fear, arousal and affective disturbances are all subject to vary if the pregnant animal is subjected to periods of aversive stimulation. Beginning in 1997, Michael Meaney of McGill University produced a series of publications suggesting that peri-natal events influence offspring and infant development, not via physical discomfort or physiological disturbance, but does so through modifications of maternal behaviour. Highly nurturant mothers (those who engage in active arched-back nursing (ABN), and spend more time licking and grooming (L/G) their pups), programme their offspring with improved cognitive abilities, decreased anxiety and fear, and reduced HPA axis hormone secretion. Low-nurturant mothers, who engage in less ABN and less L/G, tend to programme the opposite responses in their offspring. Our initial foray into this field was to investigate if gestational stress might also produce responses in the offspring via changes in maternal behaviour, and indeed ABN and L/G were reduced in dams which were subjected to gestational stress. We queried why stressed Dams would be less maternal towards their infants, and tested gestationally-stressed Dams in the Porsolt test for depressive-like behaviour. Our results suggested that these stressed Dams were actually depressed and this resulted in less maternal behaviour. Human mothers with depression are also less maternal and have been shown to divest themselves of infant care much like our prenatally-stressed Dams. On this basis we have proposed that gestational stress induced decrements in maternal behaviour represent a novel rat model for postnatal depression with face and construct validities. In the present work we have attempted to replicate the findings of Smythe¿s group (Smith et al., 2004), and have investigated the potential for antidepressants to alter the influence of gestational stress on maternal behaviours and depressive-like response, and whether or not the offspring¿ are modified by maternal treatment with ant-depressants. Approximately 140 time-mated, lister hooded rats were generated in house, and subjected to gestational stress on days 10-20 (1hr restraint/day) or remained undisturbed in their home cages. Following birth, cohorts of control and stressed Dams were administered vehicle or an antidepressant (imipramine 15mg/kg; or sertraline 10mg/kg) once daily until postnatal day 10. We assessed maternal Porsolt activity, nurturance (ABN, L/G, nest building) and anxiety-like behaviour in the elevated plus maze (EPM). Representative offspring of each Dam¿s treatment conditions were maintained post weaning and assessed in the Porsolt and EPM to determine if any changes in maternal behaviour elicited by the antidepressants altered their behavioural programming. Our findings confirm that Dams show depressive-like symptoms following gestational stress, and that administration of antidepressants to the Dams reduces depressive-like behaviour and increased maternal care. We propose that rat gestational stress is a putative model for human postnatal depression. Prenatal stress effects on maternal behaviour in the rat Dam represent a novel, and innovative model for human postnatal depression.
    • The Early Medieval Cutting Edge of Technology: An archaeometallurgical, technological and social study of the manufacture and use of Anglo-Saxon and Viking iron knives, and their contribution to the early medieval iron economy.

      McDonnell, Gerry; Taylor, Timothy F.; Batt, Catherine M.; Blakelock, Eleanor S. (University of BradfordDivision of Archaeological, Geographical and Environmental Sciences, 2013-03-26)
      A review of archaeometallurgical studies carried out in the 1980s and 1990s of early medieval (c. AD410-1100) iron knives revealed several patterns, with clear differences in knife manufacturing techniques present in rural cemeteries and later urban settlements. The main aim of this research is to investigate these patterns and to gain an overall understanding of the early medieval iron industry. This study has increased the number of knives analysed from a wide spectrum of sites across England, Scotland and Ireland. Knives were selected for analysis based on x-radiographs and contextual details. Sections were removed for more detailed archaeometallurgical analysis. The analysis revealed a clear change through time, with a standardisation in manufacturing techniques in the 7th century and differences between the quality of urban and rural knives. Analysis of cemetery knives revealed that there was some correlation between the knife and the deceased. Comparison of knives from England, Dublin and Europe revealed that the Vikings had little direct impact on England¿s knife manufacturing industry, although there was a change in manufacturing methods in the 10th century towards the mass produced sandwich welded knife. This study also suggests that Irish blacksmiths in Dublin continued their ¿native¿ blacksmithing techniques after the Vikings arrived. Using the data gathered a chaîne opértoire of the iron knife was re-constructed, this revealed that there was a specific order to the manufacture process and decisions were not only influenced by the cost of raw materials, the skill of the blacksmith and the consumer status, but also by cultural stimulus.
    • Early prehistoric petrology: A case study from Leicestershire.

      Gibson, Alex M.; Cotton, David E.; Parker, Matthew J. (University of BradfordArchaeological and Environmental Sciences, School of Life Sciences, 2014-05-06)
      This research focused on the petrographic analysis of prehistoric ceramics within the East Midlands. Prior assessments have been intermittent and not drawn together by a research-based agenda, with a few notable exceptions. This research uses petrographic analysis to shed light on early prehistoric society within Leicestershire, a county overlooked in comparison to other regions. The aim of this research was to investigate the procurement of raw materials and the subsequent production of Neolithic and early Bronze Age ceramics in Leicestershire, placing the county in its regional context. Petrographic slides from several early prehistoric sites were produced and analysed to determine the presence of any non-local material within the fabric of the ceramics. Existing petrographic data from other sites in the East Midlands were used as a comparative data set to test whether the ceramics from Leicestershire were typical or atypical of the wider production and procurement pattern. The results of the petrographic analysis on the Leicestershire sites indicated that the clay and inclusions were most likely of local origin, with no definitive evidence for non-local inclusions. However, the results from the comparative petrographic data obtained from sites within the wider East Midlands does support the movement of raw materials and/or finished ceramic products within the region. Preferential sources appear to have been continually exploited, both chronologically and geographically. The prime target of the exploitation was the Charnwood Forest area of Leicestershire, with groups from Derbyshire and Nottinghamshire utilising this resource in addition to more local groups within Leicestershire.
    • The ecology and management of feral cat colonies. A survey of feral cat colonies in Great Britain and an experimental field study of the effect of neutering on the ecology, behaviour and social organisation of a single colony.

      Delany, M.J.; Rees, Paul Anthony (University of BradfordPostgraduate School of Studies in Environmental Science, 2010-02-10)
      A postal questionnaire survey located over 700 feral cat colonies. Most were small well - established and lived in association with man, The feral cat population of Britain was estimated to be one million and is concentrated in urban areas. A domestic cat survey indicated a total population of 5.9 million cats in Britain. There appeared to be more females than males and a higher proportion of females than males were neutered. The effect of neutering on a colony of 30 adult cats. living in the grounds of Winwick Hospital, Cheshire, was examined. Individual cats were recognised by differences in coat colour and pattern, and data were collected by direct observation. The colony was studied for one year before and one year after neutering. Before neutering there appeared to be a seasonal fluctuation in numbers as a result of natality$ mortality and migration. Male immigrants were recorded. After neutering the colony remained stable in size and only one (female) immigrant was observed. The ecology and behaviour of 19 cats were studied in terms of home range, the distribution of, sightings in time, and sociability. Before neutering cluster analysis was used to identify groups of similar cats: males$ femalesp nomads and residents, After neutering no such groups could be distinguished and it is suggested that this was a result of changes in hormone balance. A mathematical model was developed for the study of associations within populations. It was shown that the cats tended to form more discrete social groups after neutering with fewer movements between groups. The adult cats were generally in good condition but there was evidence of exposure to feline calicivirus and feline herpesvirus. Trapping of cats appeared to be efficient and humane, and neutering was considered to be an acceptable form of population management.
    • An economic analysis of foreign tourism to Greece. An examination of the growth and structure of foreign tourism to Greece 1960-84 with a planning model and marketing policy recommendations.

      Buckley, Peter J.; Mirza, Hafiz R.; Witt, S.F.; Papadopoulos, Socrates l. (University of BradfordPostgraduate School of Studies in Management and Administration, 2011-08-01)
      Tourism - in particular its determinants and effects - is an issue presently attracting much attention worldwide. International tourism is considered to be the largest single item of the world's foreign trade and for some countries it is the most important export industry and earner of foreign exchange. In addition to its economic significance, tourism contributes to the quality of life. It produces intangible benefits which are directly related to the physical and psychological health of people, and the enjoyment of the right to rest and free time. This applies with equal validity to both domestic and international tourism; the latter establishing international economic, political and socio-cultural links, as well as strengthening the domestic character of a nation. At the individual level, tourism satisfies the need to travel in search for relief from the stress of work and the routine of daily life in the big urban centres. At macro (country) level, tourism is, therefore, a human and economic activity which concerns most of us in many parts of the world, directly or indirectly. One country for which foreign tourism is of considerable importance is Greece. In order to identify likely supply constraints (e. g. tourist accommodation and basic infrastructure) and to establish the major market segments of Greek tourism, the growth and structure of foreign tourism in Greece between 1960 and 1984 is examined. Special attention is given to the magnitude of tourism in Greece and its economic effects on the national economy. The non-economic effects of tourism are also considered. This is followed by the construction of a tourist profile so that the types of foreign visitors that go to Greece are identified. Subsequently, an econometric model is developed and empirical results provided to explain foreign tourist arrivals in Greece and to assess the impact of promotional expenditure by the Greek National Tourist Organisation in a number of foreign tourist generating markets. Finally, a tourism marketing planning model is devised which highlights the main variables affecting the international tourism marketing policies of the Greek National Tourist Organisation and, in particular, empirical results are used in conjunction with- a tourism market choice matrix for selecting market targeting strategies. The major conclusion emerging from the research is that as the tourist industry in Greece is of vital importance, the adoption of a strategic, interdisciplinary and integrated tourism planning process along with the establishment of a tactically orientated task unit could provide important improvements in the effectiveness and contribution of tourism in Greece. A few proposals regarding future policies by the Greek authorities are made, such as the establishment of a co-ordinating body orchestrating the efforts of the appropriate groups relevant to the multifaceted nature of tourism.
    • Educating on the edge of chaos. Using complexity theory to examine pedagogical responses to global complexity by peace educators.

      Not named; Romano, Arthur (University of BradfordDepartment of Peace Studies, 2013-11-28)
      This dissertation examines the nexus of complexity theory and peace education and its implications for developing educational praxis that engages with the demands of global complexity. In this thesis, I argue that as societies become more globalized and complex (global complexity) there is an onus upon education to adapt its methods so people can understand the workings of these processes better and further develop the ethical and creative resources needed for responding to system dynamics effectively. My central thesis is that the most appropriate way to do this is to use methods that are congruent with the subject matter of global complexity¿that is to align ones pedagogy with one¿s subject area. This dissertation therefore investigates the situated and contingent responses of peace educators working in the field to the challenges and opportunities that arise when attempting to adapt to local/global dynamics. It utilizes ethnography, narrative inquiry, and autoethnography and draws its data from interviews with over 50 educators in India, Japan, and the US. This research demonstrates that when engaging with global complexity, peace educators adapt both their ontological understanding and methodological orientation in ways congruent at times with the insights of complexity theory. While this understanding can be at odds with mass educational methodologies, this tension also is a touchstone for peace educator¿s creative formulation of novel praxis in response to the demands of global complexity. This dissertation thus examines some of the possibilities for learning within complex knowledge production systems and highlights the need for further research into the dynamics and processes at play within global educational ¿networks.¿
    • Education and Security: Design and Evaluation Tools for Deliberate Disease Risks Mitigation

      Whitby, Simon M.; Mancini, Guilio M. (University of BradfordFaculty of Social Sciences, 2016)
      This thesis addresses the role of education to mitigate the risks of deliberate disease, including biological weapons. Specifically, it aims to analyse how education was constructed as a potential instrument to mitigate specific security risks; if and how education could impact on risks; and how effectiveness of education as a risk mitigation measure could be improved. The research framework combines concepts of security, risk and education within a general constructionist approach. Securitization is used to analyse attempts to construct education as a tool to mitigate specific security risks; risk assessment is used to identify and characterize risk scenarios and potential for risks mitigation; and instructional design and evaluation models are used for the design and evaluation of education. The thesis contends that education has been constructed as a mitigation tool for what were presented as urgent security risks of deliberate disease. Nine attempted securitization moves are identified and assessed. Improved competences identified in four thematic areas, and built with education, can mitigate risks in specific scenarios via impacting factors that primarily influence risk likelihood. The thesis presents several examples of achieved learning objectives, and tools that can be useful to evaluate behavioural and risk impacts, though empirical results on these levels here are still scarce. Design and evaluation tools, illustrated through a large amount of original and pre-existing data from a range of countries and contexts, are presented that can improve effectiveness of education as a deliberate disease risks mitigation measure.
    • The educational and occupational aspirations of young Sikh adults. An ethnographic study of the discourses and narratives of parents, teachers and adults in one London school.

      Burkitt, Ian; Sullivan, Paul W.; Brar, Bikram S. (University of BradfordDepartment of Social Sciences and Humanities, 2013-12-05)
      This research study explores how future educational and occupational aspirations are constructed by young Sikh adults. Semi-structured interviews were conducted with ten young Sikh adults, both their parents, and their teachers at one school in West London to investigate how future aspirations are constructed, which resources are employed, and why certain resources are used over others. In some previous research on aspirations and future choices, Sikhs have either been ignored or, instead, subsumed under the umbrella category of ¿Asian¿ and this study seeks to address this. Furthermore, the study seeks to shed light on how British-Sikh identities are constructed and intersected by social class, caste and gender. This is important to explore since it can have an impact upon how young adults are structured by educational policy. A ¿syncretic¿ social constructionist framework which predominantly draws upon Pierre Bourdieu¿s notions of habitus, capital and field, along with the cultural identity theories of Avtar Brah and Stuart Hall, is employed to investigate the construction of identities and aspirations. In addition, the study contains ethnographical elements as it is conducted on my ¿own¿ Sikh group and at my former secondary school. Consequently, I brought a set of assumptions to the research which, rather than disregard, I acknowledge since they highlight how I come to form certain interpretations of phenomena over others.
    • The educational theories of Rudolf Steiner. An exposition of the concepts fundamental to Steiner's theories and an examination of their validity by means of a comparison with the theories of other educationalists.

      Curle, Adam; Flood Page, C.; Mollet, David L. (University of BradfordPostgraduate School of Studies in Peace Studies, 2010-02-04)
      The main thesis deals with the educational theories of Rudolf Steiner. These theories are dealt with in Parts III to VIII of the thesis. Before this, in Part 1, there occurs a brief description of the background and life of Steiner; and, in Part II, a,, philosophical discussion of the basic tenets and assumptions upon which Steiner's educational theories rest. The areas dealt with in Parts III to VIII are divided into three. The first is an exposition of Steiner's ideas; the second is a comparison and appraisal of Steiner's theories with other educationalists; the third is an examination and evaluation of some of the concepts which are fundamental to Steiner's theories. The first of these areas i. e. the exposition of Steiner's ideas, is subdivided into three: his views on the nature of the child and the'way in which the child grows and develops; methodologies of teaching; and content and curriculum. An exposition of Steiner's theories on the nature of the child and its development occurs in Part III. - This is followed, in Part IV, by an evaluation of his theories by comparing them with other educationaliits. In Part V an examination of Steiner's theories on methodologies of teaching, by considering his views of "The Temperaments", occurs; - reference and comparisons to other educationalists are made in the same section. In. Part VI descriptions of the Waldorf curriculum are given and this is followed by an evaluation at the end of the section. The evaluation examines 'a number of concepts upon which the Waldorf curriculum has bpen formulated in the context of modern day curriculum objectives, design and learning experiences. In Part VII a brief historical perspective : is obtained of Steiner's theories by comparing his views with those of Plato, Rousseau and Montessori. This perspective is placed in a modern day context in Part VIII, and is obtained by an examination of many of the concepts fundamental to Steiner's theories. This includes a detailed critique of two of the main assumptions upon which Steiner's theories of education rest; an examination of the relationship of the individual to society in an educational context; and a discussion of the nature and aims of the educational process.
    • The effect of Basel II on SME financing in Germany. An exploratory study of the impact of the new Basel Accord on SMES and financiers in Germany

      Letza, Steve; Pike, Richard H.; Schmid, Bernhard (University of BradfordSchool of Management, 2011-11-14)
      The New Capital Accord (henceforth, Basel II), is expected to impose dramatic changes on banks and other providers of corporate financing, as well as companies. Literature indicates that small and medium sized enterprises (henceforth SMEs), in general, and in particular German SMEs seem to be affected: Germany has the highest SME density with SMEs comprising 99.6% of all corporations (IMF, 2008), these SMEs are highly dependent on banks for financing (see Jacobson et al, 2006). However, there is huge controversy in the literature concerning how these changes will look, right before Basel II came into effect in the years 2007 / 2008 in the European Union. In order to explore this effect from a Post-Basel II perspective, the objective of this research project is to establish what effect Basel II will have on corporate financing of SMEs in Germany. The high impact on SMEs (in Germany), combined with controversial evidence from extant Pre-Basel II research, indicates a high relevance to academics and practitioners for this thesis. This thesis is probably the first from a Post-Basel II perspective which covers both the SMEs' as well as the financiers' perspective. Based on a structured literature review using the comparative method (Peters, 1998) 'Most Different Systems' evidence is provided that there is no consistent picture regarding the effect of Basel II. Therefore, further research is needed to determine whether the effect in Germany is consistent, from a Post-Basel II perspective, with regards to the conditions which trigger certain mechanisms, from a 'scientific realism' (Smith, 1998) perspective, because the literature indicates that 'positivist generalising' has limited validity. Building on Creswell (2003), an 'exploratory sequential' design was created to test three initial hypotheses (as confirmation or refutation of a theory, see Gujarati, 2003:8): a multi-method design is best suited to the author's philosophical stance of 'scientific realism' by means of triangulation (Robson, 2002:174). The result of the initial quantitative phase is based on the analysis of questionnaire data from 125 SMEs and financiers (banks, private equity companies, family offices, providers of alternative means of financing) derived from a probabilistic sample frame in the fourth quarter of 2008. Mathematical models for SMEs and financiers regarding the three initial hypotheses were set-up and tested using the appropriate statistical tests. In order to limit bias by means of a spill-over effect from the financial crises, control questions were used. The subsequent qualitative phase by means of semistructured elite interviews (Saunders et al, 2007:312) between March and May 2009 enabled a valid triangulation and provided in-depth insights into how SMEs can cope best with Basel II. The purposive sample, of 17 'important cases', included company owners and top-level financier executives. In a conclusive quantitative and qualitative synopsis, the three initial hypotheses were acknowledged. However, the qualitative in-depth analysis by means of 'causal networks' (Miles and Huberman, 1994) led to an amendment of the hypotheses as follows: 1. Corporate finance has become different for SMEs because the 'house bank principle' has changed to a 'core bank principle' due to Basel II. Shopping around regarding credits will be more difficult which makes financing more difficult. This could be overcompensated by major SMEs, by using non-credit corporate financing which leads to a reduction of the 'house bank' principle. 2. SMEs can cope best with the effect when they: a) proactively engage in rating and improve the parameters, or b) they adjust their strategy as stated in hypothesis 3. 3. Financiers (especially non-bank financiers) will engage in SME corporate finance when they have a sound financial basis / management and when they adjust their strategy in terms of growth with the aim of niche market leadership and when they open up for exit strategies.
    • The effect of clearance upon friction and lubrication of large diameter hip resurfacing prosthesis using blood and combinations of bovine serum with aqueous solutions of CMC and hyaluronic acid as lubricants.

      Youseffi, Mansour; Afshinjavid, Saeed (University of BradfordSchool of Engineering, Design and Technology, Medical Engineering Department, 2011-06-16)
      In real life, immediately after joint replacement, the artificial joint is actually bathed in blood (and clotted blood) instead of synovial fluid. Blood contains large molecules and cells of size ~ 5 to 20 2m suspended in plasma and considered to be a non-Newtonian (pseudoplastic) fluid with density of 1060 Kg/m3 and viscosity ~ 0.01 Pas at shear rates of 3000 s-1 (as obtained in this work). The effect of these properties on friction and lubrication is not fully understood and, so far to our knowledge, hardly any studies have been carried out regarding friction of metal-on-metal bearings with various clearances in the presence of lubricants such as blood or a fluid containing macromolecules such as hyaluronic acid (HA) which is a major component of synovial fluid increasing its viscosity and lubricating properties. In this work, therefore, we have investigated the frictional behaviour of a group of Smith and Nephew Birmingham Hip Resurfacing implants with a nominal diameter of 50mm and diametral clearances in the range ~ 80 2m to 300 2m, in the presence of blood (clotted and whole blood), a combination of bovine serum (BS) with hyaluronic acid (HA) and carboxymethyl cellulose (CMC, as gelling agent) adjusted to a range of viscosities (~0.001-0.2 Pas), and bovine serum with CMC adjusted to a similar range of viscosities. These results suggested that reduced clearance bearings have the potential to generate high friction especially in the presence of blood which is indeed the in vivo lubricant in the early weeks after implantation. Friction factors in higher clearance bearings were found to be lower than those of the lower clearance bearings using blood as the lubricant. Similar trends, i.e. increase in friction factor with reduction in diametral clearance, were found to be also the case using a combination of BS+CMC or BS+HA+CMC as lubricants having viscosities in the range 0.1-0.2 and 0.03-0.14 Pas, respectively. On the other hand, all the lubricants with lower viscosities in the range 0.001-0.0013 and 0.001-0.013 Pas for both BS+CMC and BS+HA+CMC, respectively, showed the opposite effect, i.e. caused an increase in friction factor with increase in diametral clearance. Another six large diameter (50mm nominal) BHR deflected prostheses with various clearances (~ 50-2802m after cup deflection) were friction tested in vitro in the presence of blood and clotted blood to study the effect of cup deflection on friction. It was found that the biological lubricants caused higher friction factors at the lower diametral clearances for blood and clotted blood as clearance decreased from 2802m to 502m (after deflection). The result of this investigation has suggested strongly that the optimum clearance for the 50 mm diameter MOM BHR implants to be ¿1502m and <2352m when blood lubricant used, so as to avoid high frictions (i.e. avoid friction factors >0.2) and be able to accommodate a mixed lubrication mode and hence lower the risk of micro- or even macro-motion specially immediately after hip implantation. These suggested optimum clearances will also allow for low friction (i.e. friction factors of <0.2-0.07) and reasonable lubrication (dominantly mixed regime) for the likely cup deflection occurring as a result of press-fit fixation.
    • The effect of eicosapentaenoic acid on brain and platelet produced bioactive lipid mediators. The effect of eicosapentaenoic acid, docosapentaenoic acid and other polyunsaturated fatty acids on the eicosanoids and endocannabinoids produced by rat brain and human platelets using electrospray ionisation tandem mass spectrometry-based analysis.

      Nicolaou, Anna; Blagden, Nicholas; Mir, Adnan A. (University of BradfordBradford School of Pharmacy, 2010-04-01)
      Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (PUFA) with neuroprotective and cardioprotective properties. It is thought that some of the actions of EPA may be attributed to its elongated metabolite, the PUFA docosapentaenoic acid (DPA). Docosahexaenoic acid (DHA) and arachidonic acid (AA) are bioactive PUFA ubiquitously expressed in neural tissues. EPA and AA can be converted by cyclooxygenase (COX) to prostanoids and by lipoxygenase (LOX) to hydroxy fatty acids. PUFA can also be converted to ethanolamides in the brain. These mediators are involved in physiological and pathological processes in many bodily systems. The purpose of this study was to examine the production of eicosanoids, hydroxy fatty acids and fatty acid ethanolamides in young and aged rat brain following EPA or DPA enriched diets. The effects of specific PUFA on human platelet eicosanoid production were also investigated as these mediators play a role in adhesion and aggregation. Liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) assays were developed and used to measure lipid mediators in rat brain and human platelets. Ageing in rat brain was accompanied with several changes in the prostanoid and hydroxy fatty acid profiles. Supplementing the diet with EPA or DPA at a daily dose of 200 mg/kg for 8 weeks prevented these changes and decreased levels of PGE2. DPA changed the profile of hydroxy fatty acids synthesised in the brain tissue of young animals. This study has shown that levels of eicosapentaenoylethanolamide (EPA-EA) increase in the brain as a result of ageing and that this is accompanied by an increase in levels of anandamide. Feeding aged animals EPA or DPA further increased the levels of EPA-EA but prevented any change in the level of anandamide. Niacin is used to treat hypercholesterolaemia although it is associated with an unpleasant PGD2 mediated skin flush. This exploratory study has shown that human platelets treated with niacin did not show any changes in their prostanoid and hydroxy fatty acid profiles. Platelets treated with EPA showed increased production of TXB3 and 12-HEPE. Niacin augmented the effects of EPA on human platelet mediator synthesis. Overall, this study has demonstrated that EPA can change brain and platelet lipid mediator synthesis and has provided evidence that could explain some of the neuroprotective and cardioprotective actions of this PUFA.
    • The effect of monolingualism, bilingualism and trilingualism on executive functioning in young and older adults

      Lesk, Valerie E.; Guðmundsdóttir, Margrét Dögg (University of BradfordDivision of Psychology Faculty of Social Sciences, 2015)
      Bilinguals have been posited to have, compared to monolinguals, enhanced cognitive control, consequently exhibiting greater cognitive reserve, which is thought to subsequently delay the onset of clinical expression of dementia. Based on recent evidence suggesting that the more languages one manages the greater cognitive reserve, and that trilinguals undergo greater exercise in language control than bilinguals, this thesis investigated the effects of trilingualism and ageing on cognitive control, in young adults to older adults. As the thesis investigated the novel field of trilingualism and cognitive control, task complexity, the age of second and third language acquisition, language use, and physical and cognitive activity were also, importantly, assessed, as these are possible influencing factors in test performance. The participants completed several cognitive tasks; namely the Simon task, the Inhibition of return task, the Stroop task (inhibition) and the N-back task (working memory). The novel discovery of a trilingual (and bilingual) disadvantage was observed, which could explain some previous inconsistent findings in the bilingualism literature, where trilingualism may influence bilinguals’ test performance, as trilinguals and multilinguals are often mixed in with the bilingual group. Furthermore, the results suggest that second language acquisition and language use does not consistently predict performance in trilinguals (and bilinguals), nor does cognitive activity, although physical activity may modulate language group differences. Importantly, the results from this novel investigation of the effects of trilingualism and ageing on cognitive control suggest that trilingualism (and bilingualism) can, in some cases, be detrimental to cognitive control.
    • Effect of nanoparticles on human cells from healthy individuals and patients with respiratory diseases.

      Anderson, Diana; Thorning, Paul; Osman, Ilham F. (University of BradfordBiomedical Sciences, 2011-04-08)
      Ever increasing applications of nanomaterials (materials with one or more dimension less than 100 nm) has raised awareness of their potential genotoxicity. They have unique physico¿chemical properties and so could have unpredictable effects. Zinc oxide (ZnO) and titanium dioxide (TiO2) are widely used in a number of commercial products. There are published studies indicating that some forms of these compounds may be photo-clastogenic in mammalian cells. What has not been investigated before is the effect of nanoparticles from these compounds in human germ cells. Thus the present study has examined their effects in the presence and absence of UV light in human sperm and compared responses to those obtained with human lymphocytes using the Comet assay to measure DNA damage. The effect of nanoparticles (40-70nm range) was studied in human sperm and lymphocytes in the dark, after pre-irradiation with UV and simultaneous irradiation with UV. The studies do provide some evidence that there are photo-genotoxic events in sperm and lymphocytes in the absence of overt toxicity. The cytotoxic and genotoxic potentials of ZnO and TiO2 as well as their effect on phosphotyrosine expression, were examined in the human epithelial cervical carcinoma cells (Hela cells). This was done to try and determine the underlying molecular events resulting from their exposure to ZnO and TiO2 nanoparticles occurring at the same time as DNA is damaged. Concentration- and time-dependent cytotoxicity, and an increase in DNA and cytogenetic damage with increasing nanoparticle concentrations were reported in this study. Mainly for zinc oxide, genotoxicity was clearly associated with an increase in tyrosine phosphorylation. Nanotechnology has raced ahead of nanotoxicology and little is known of the effects of nanoparticles in human systems, let alone in diseased individuals. Therefore, the effects of TiO2 nanoparticles in peripheral blood lymphocytes from patients with respiratory diseases (lung cancer, chronic obstructive pulmonary disease (COPD) and asthma) were compared with those in healthy individuals using genotoxic endpoints to determine whether there are any differences in sensitivity to nano-chemical insult between the patient and control groups. The results have shown concentration dependent genotoxic effects of TiO2 in both respiratory patient and control groups in the Comet assay and an increasing pattern of cytogenetic damage measured in the micronucleus assay without being statistically significant except when compared with the untreated controls of healthy individuals. Furthermore, modulation of ras p21 expression was investigated. Regardless of TiO2 treatment, only lung cancer and COPD patients expressed measurable ras p21 levels that showed modulation as the result of nanoparticle treatment. Results have suggested that both ZnO and TiO2 nanoparticles can be genotoxic over a range of concentrations without either photoa-ctivation or being cytotoxic.
    • The Effect of oestrogen in a series of models related to schizophrenia and Alzheimer¿s disease. A preclinical investigation into the effect of oestrogen on memory, executive function on and anxiety in response to pharmacological insult and in a model of natural forgetting.

      Neill, Joanna C.; Marshall, Kay M.; Cook, Samantha (University of BradfordSchool of Pharmacy, 2013-03-05)
      Alzheimer¿s disease is associated with aging and is characterised by a progressive cognitive decline. Its onset in women coincides with the abrupt depletion of ovarian steroids prompting the investigation of utilising oestrogen replacement therapy as restoration or a preventative measure. Gonadal steroids have also recently been implicated in other disease states, particularly schizophrenia. In addition to the cognitive decline, sufferers of Alzheimer¿s disease and schizophrenia display anxiety related behaviour which gonadal steroids have also been shown to ameliorate. In this thesis several paradigms were used to investigate the effects of oestradiol benzoate (EB) on cognition and anxiety, utilising the NMDA receptor antagonist PCP, the muscarinic receptor antagonist scopolamine and the dopamine releasing agent amphetamine to induce a cognitive deficit in rats by different pharmacological mechanisms. The thesis also investigated the effects of EB on a delay dependent cognitive deficit model of forgetfulness in natural aging. Results showed that subchronic PCP dosing failed to induce a significant deficit in the novel object recognition task. Locomotor activity tests demonstrated that the PCP treated rats were sensitised to the treatment suggesting that the PCP dosing regimen was successful. There was no significant effect of oestrogen in the reversal learning model or in the plus maze task designed to explore EB¿s effects on anxiety. However, in the latter task there was a trend towards an anxiogenic effect of EB. Results from the delay dependent model of forgetfulness in natural aging demonstrated that EB could enhance recognition memory, but not spatial memory. The results are discussed in the context of the role of gonadal steroids especially oestrogen in combating the cognitive decline seen in schizophrenia, neurodegenerative disease and natural aging.
    • The effect of oxidative stress in lymphocytes from patients with inflammatory bowel disease and various cancer states compared with healthy control individuals.

      Anderson, Diana; Najafzadeh, Mojgan (University of BradfordSchool of Life Sciences, Biomedical Sciences, 2012-01-11)
      In the present investigation peripheral blood lymphocytes from patients with inflammatory bowel disease (IBD) and different cancer states were treated with various agents and compared with lymphocytes from healthy control individuals (HCI) treated in the same way and measured in the Comet assay. For inflammatory bowel disease, patient¿s responses in IBD patients treated with H2O2 were higher than in HCI and crohn¿s patients (CD) were found to have higher responses than Ulcerative colitis (UC) patients. The responses for all IBD and HCI were all reduced in the presence of chaga mushroom extract which behaved in an antioxidant manner. A second group of IBD patients were treated with the heterocyclic amine (food mutagen), IQ and H2O2 and responses were reduced in the presence of the flavonoids, quercetin and epicatechin and compared with HCI similarity treated. In all cells responses were reduced with flavonoids and again CD had higher responses than the UC patients and IBD patients higher than HCI. The responses with CD and UC were that confirmed in two independent studies with IBD, one with chaga mushroom extract and the other with flavonoids. Peripheral lymphocytes from malignant melanoma and suspected melanoma patients and colon cancer and polyposis patients were compared to the lymphocytes from HCI and treated with UVA. There were differential sensitivities when measured in the micronucleus and Comet assays. The cancer patients had higher responses than those in the precancerous states and they in turn were higher than responses in HCI. In all the studies, untreated baseline DNA damage values were also higher in IBD and cancer patients and pre-cancerous patients than HCIs. This would suggest that baseline frequencies of different diseases compared to controls could be an important biomarker in the diagnosis of pre-cancers and early stage cancers. Also peripheral lymphocytes are a useful surrogate for cancers and pre-cancerous disease states since, blood is present in all organs and tissues and DNA is basically the same in all cells.
    • The Effect of PEG-Insulin and Insulin Hexamer Assembly on Stability in Solution and Dry Powders. Hexamer Assembly of PEGylated-Insulin and Insulin Studied by Multi-Angle Light Scattering to Rationally Choose the pH and Zinc Content for Analytical Methods and Formulations of Dry Powders.

      Forbes, Robert T.; Kuo, Mei-Chang; Bueche, Blaine (University of BradfordThe School of Pharmacy, 2013-11-20)
      The objective of this research is to further define the relationship between the charge state of insulin, and the self assembly properties of insulin and PEGylated insulin in solution. Polyethylene glycol (PEG) chains were covalently attached to insulin in order to evaluate their impact on insulin¿s systemic duration of action after pulmonary dosing. This thesis will focus on the assembly properties of the PEG-insulin and insulin, and also demonstrate how the charge state, which was modified by the covalent attachment of PEG, relates to different modes of behavior by anion and cation exchange chromatography. In addition, explain how modifying the assembly state extends to improving formulation properties of spray-dried insulin powders. This thesis is an investigation into the relationship of insulin¿s charge state controlled by pH and how the charge state affects the self assembly of insulin, especially when the zinc ion is removed. Ionic interaction is one of the major forces affecting insulin assembly. The theory that a change in the charge state of insulin could modulate the ionic interaction and reduce hexamer formation at alkaline conditions was investigated. Experiments were designed to measure the level of hexamer with light scattering, and the amount of hexamer was then correlated with the pH and zinc content of the solutions. The importance of the charge state of the monomer and its behavior extends to chromatography and purification modes as well. Specifically, the purification of various species of PEGylated insulin presents a challenge. By varying mobile phase pH which induces the charge to insulin, an ion exchange method demonstrated very high resolution and controllable interaction between the ion exchange media and the insulin derivatives. A highly accurate method for determining molecular weight and thus the average associated state of insulin in solution has been developed using the MALS (Multi-Angle Light Scattering). Insulin concentration, pH, and metal ion concentrations, were in pharmaceutically relevant ranges. The MALS method was developed to evaluate how the parameters above affect the self-assembly properties of insulin, and use the assembly properties to improve formulations of insulin or PEGylated insulin. To use the light scattering technique the dn/dc (change in refractive index with change in concentration) is required. During the method development, the dn/dc of insulin was measured at 690 nm, and a value of 0.185 mL/g based on theory was confirmed. A novel approach for preparing insulin powders with improved chemical stability, based on maintaining the dissociation of hexamers in solution during the spray drying process was developed. The mode presented here is to remove the zinc ions from solution, increase the pH from 6.6 to 7.8, and maintain a low concentration of insulin approximately 2 to 15 mg/mL. Each of these factors alone decreases the hexamer population in solution, but by combining all three factors, hexamers are driven to very low levels of equilibrium. The increased stability of the powders is predominately related to the decrease in covalent insulin dimer (CID). The data presented correlates a reduced hexamer population in the solution with lower levels of CID¿s in the dry powder compared to controls. The CID formation rate was reduced by 40% compared to a control.
    • Effect of post-harvest treatment on ripening and quality of tomato fruit using ozone. Application of different ozone doses as controlled atmosphere storage for delay ripening and maintaining the quality of tomatoes and effect of ozone on antioxidant and sugar compounds at different stages of tomato fruit ripening.

      Karodia, Nazira; Tizaoui, Chedly; Shalluf, Milad A. (University of BradfordSchool of Engineering, Design and Technology, 2010-10-15)
      Tomatoes are widely produced and consumed due to their nutritional content and versatility. However, the tomato is a soft fruit liable to damage and flavour deterioration. Hence, the main challenge for the tomato producing industry is to prevent the high loss incurred during harvest, handling and transportation of the crops. The objective of this study was to investigate the overall nutritional implication of controlled storage of tomatoes using ozone on the ripening process and the basic nutritional components of tomatoes. This investigation was also designed to focus on the effect of different ozone doses on the basic components and properties (carotenoids, ascorbic acid, total antioxidant activity and soluble sugars content) of the quality and dynamic maturity of tomatoes. Green tomatoes (Rio Grande) were treated in glass chambers with ozone enriched air [(air + 2, 7 and 21 mg O3/g tomato) and control (air only)] under humidity and temperature of 90-95% and 14-17 oC respectively. Tomatoes were sampled after 14 days of ozone treatment in the storage chamber and analyzed for different quality parameters (appearance, weight loss, Total Soluble Solids (TSS), titratable acidity, total ascorbic acid and carotene) of the ripening. The variety Elegance tomatoes were selected and the fruits were graded by colour and subjected to treatment with ozone (in doses 0 (clean air), 0.25, 0.50, and1.00 mg O3/g tomatoes) during storage for 6 days under the same humidity and temperature conditions. The fruits were analysed for carotenoids, ascorbic acid content, total antioxidant activity and soluble sugars.Analysis of the fruits clearly showed that ozone significantly delayed the development of colour on the surface, particularly in the low doses, and caused black spots on the surface of the tomatoes, particularly in higher ozone doses. Ozone did not affect the ascorbic acid and titratable acidity content. However ozone did reduce the Total Soluble Solids (TSS) by about 10% at the lowest ozone dose. A high inhibition of accumulation of carotenoids, particularly at low dose, of the tomatoes (Rio Grande) was also observed. Tomatoes (Elegance) under ozone treatments contained higher ß-carotene than those under the control treatment and lycopene content increased during storage in the red stage of tomato fruits. Ascorbic acid (AsA), dehydroascorbic acid (DHA) and the total of AsA and DHA concentrations, and ratios of redox (ASA/ (ASA + DHA) and DHA/AsA in pericarp and pulp of tomatoes tissue, did not show clear differences between the different treatments. The concentrations of the glucose and fructose increased in the tomatoes which were subjected to ozone treatments. Results from this study show that controlled atmosphere storage of tomatoes using ozone is a viable technique which warrants further study.
    • The effect of prostaglandins in myometrial tissue; a functional and lipidomic study. The influence of the hormonal milieu on the functional response to prostaglandins and ex vivo lipid biosynthesis in myometrial tissues.

      Marshall, Kay M.; Sabar, Uzmah Jabeen (University of BradfordBradford School of Pharmacy, 2013-11-21)
      Prostaglandins are integral mediators in reproductive processes but their exact role in uterine function is still not clear. In addition, ethical restraints have limited the availability of human tissue to investigate uterine prostanoid receptor populations. The aim of this thesis was to characterise the prostanoid receptors on the human and rat myometrium in order to evaluate the potential of the rat as an animal model of human uterine function and disease. For functional analysis of myometrial prostanoid receptors the immersion technique was utilised. LC-ESI-MS/MS was also used to measure the ex vivo myometrial release of prostanoid metabolites. The results show that both the rat and human uterus displays cyclical changes in uterine motility, with myogenicity greatest in the follicular and oestrus stages. The data also indicate that whilst the human uterus is responsive to EP3, EP2, TP, FP and IP receptor agonists, a functional population of only EP3, EP2 and FP receptors is present on the rat uterus, although the TP receptor appears to be upregulated at gestation and post-partum. The results also show that myometrial prostanoid release in the human uterus is cyclically regulated, with the greatest amount of prostaglandins being released during the late follicular stage. In conclusion, although similarities do exist with regard to the ovarian regulation of uterine motility in both the rat and human uterus, the differences in the apparent functional prostaglandin receptor populations between the two species suggest further work is required before the rat can be used as a model of human uterine function.