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  • The Role of vision and refractive correction changes in dizziness

    Elliott, David B.; Alderson, Alison J.; Armstrong, Deborah (University of BradfordBradford School of Optometry and Vision Science, 2018)
    Dizziness is a common, multifactorial problem that causes reductions in quality of life and is a major risk factor for falls, but the role of vision is a very under-researched area. This study aimed to investigate any link between dizziness and vision and to establish if changes in spectacle lens correction could elicit dizziness symptoms. A link between dizziness and self-reported poor vision was indicated in the epidemiological literature as shown by a systematic review, provided lightheadedness was not included in the definition of dizziness. Cases of individuals who reported vision-related dizziness were investigated to determine potential areas of research for this thesis and subsequently two studies investigated the effects of refractive correction changes on dizziness status. The first study was limited by logistical problems, although it highlighted limitations in the short form of the Dizziness Handicap Inventory that was used to quantify dizziness. Results of an optometry practice recheck study found that oblique cylindrical changes were significantly more likely to be associated with dizziness symptoms than other spectacle lens changes. It also highlighted that optometrists do not ask/record about dizziness symptoms with only 4% of records including “dizziness” as a problem when 38% of patients reported dizziness symptoms when directly asked. All studies highlighted a need for a patient-reported outcome measure to be designed to assess vision-related dizziness. Literature review, interviews with experts and patients and focus groups led to the development of a pilot questionnaire and subsequently a 25-item Vision-Related Dizziness instrument, the VRD-25. This was validated using responses from 223 respondents, with 79 participants completing the questionnaire a second time to provide test-retest data. Two subscales of VRD-12-frequency (VRD-12f) and VRD-13-severity (VRD-13s) were shown to be unidimensional and had good psychometric properties, convergent validity and test-retest repeatability. The VRD-25 is the only patient-reported outcome measure developed to date to assess vision related dizziness and will hopefully provide the platform to further grow this under-researched area that seems likely to provide important clinical information.
  • Novel medical imaging technologies for processing epithelium and endothelium layers in corneal confocal images. Developing automated segmentation and quantification algorithms for processing sub-basal epithelium nerves and endothelial cells for early diagnosis of diabetic neuropathy in corneal confocal microscope images

    Qahwaji, Rami S.R.; Ipson, Stanley S.; Hammadi, Shumoos T.H. (University of BradfordSchool of Electrical Engineering and Computer Science, 2018)
    Diabetic Peripheral Neuropathy (DPN) is one of the most common types of diabetes that can affect the cornea. An accurate analysis of the corneal epithelium nerve structures and the corneal endothelial cell can assist early diagnosis of this disease and other corneal diseases, which can lead to visual impairment and then to blindness. In this thesis, fully-automated segmentation and quantification algorithms for processing and analysing sub-basal epithelium nerves and endothelial cells are proposed for early diagnosis of diabetic neuropathy in Corneal Confocal Microscopy (CCM) images. Firstly, a fully automatic nerve segmentation system for corneal confocal microscope images is proposed. The performance of the proposed system is evaluated against manually traced images with an execution time of the prototype is 13 seconds. Secondly, an automatic corneal nerve registration system is proposed. The main aim of this system is to produce a new informative corneal image that contains structural and functional information. Thirdly, an automated real-time system, termed the Corneal Endothelium Analysis System (CEAS) is developed and applied for the segmentation of endothelial cells in images of human cornea obtained by In Vivo CCM. The performance of the proposed CEAS system was tested against manually traced images with an execution time of only 6 seconds per image. Finally, the results obtained from all the proposed approaches have been evaluated and validated by an expert advisory board from two institutes, they are the Division of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar and the Manchester Royal Eye Hospital, Centre for Endocrinology and Diabetes, UK.
  • A Study of Translation of Measure and Prevalence of Pre-operative Anxiety, and Patients’ Preference of Non-Pharmaceutical Pre-operative Anxiety Reduction Intervention in Nigeria

    Archibong, Uduak E.; McClelland, Gabrielle T.; Dagona, Sabo S. (University of BradfordFaculty of Health Studies, 2018)
    Background: Pre-operative anxiety remains a serious problem affecting surgical patients. The prevalence rate ranges between 60% to 80% percent among western surgical patients. Nothing is known about the prevalence of pre-operative anxiety among Nigerian Hausa speaking elective surgical patients. It is also not known what non-pharmaceutical pre-operative anxiety reduction interventions are preferable in reducing their anxiety before they undergo elective surgery. Participants: Thirty adult patients scheduled to undergo elective surgery in a tertiary health facility in north eastern Nigeria. Design/procedure: The study consists of three phases: Phase 1- translating and cross-cultural validation of Amsterdam Pre-operative Anxiety and Information Scale (APAIS) into Nigerian Hausa Language. Phase 2- administering the translated scale to assess the prevalence of pre-operative anxiety among the study participants. Phase 3 - finding out which non-pharmaceutical pre-operative anxiety reduction interventions would the Hausa speaking elective surgical patients prefer in reducing their anxiety before they undergo elective surgery. Results: The translated Hausa and validated version of the scale (APAIS-H) has shown a good psychometric property with Cronbach's alpha of 0.82 for anxiety related to surgery subscale and 0.71 for information desire subscale respectively. The finding of phase 2 revealed that there is high prevalence of pre-operative anxiety among the Hausa speaking elective surgical patients. The patients' anxiety continues to increase in intensity as they approach their time of operation. Results of phase 3 shows that the Hausa speaking elective surgical patients have high preference for counselling services, information and education, video-film intervention and low preference for music therapy. Conclusion: There is high prevalence of pre-operative anxiety among the Hausa speaking elective surgical patients. It is therefore recommended that, before undergoing elective surgery, clinicians should assess the Hausa patients' pre-operative anxiety so as to provide them with their preferred pre-operative anxiety reduction interventions proportionate to their level of anxiety. The thesis argued that the translated and validated APAIS-H is be a good measure of assessment particularly of those Hausa patients who could not read and understand the English Language version of assessment tool.
  • How the New Labour Government Third Way policies (1998-2010) and the delivery of the New Deal for Communities (NDC) regeneration programme impacted on participation in health care in an area-based initiative. A longitudinal study using action-learning research methodology in a New Deal for Communities Area Based Initiative

    Chesters, Graeme S.; Greenham, Felicity J. (University of BradfordDepartment of Peace Studies and International Development, 2018)
    The research examines New Labour’s Third Way policies and the impact New Deal for Communities (NDC) regeneration programme had on participation in health care. This longitudinal study (1998-2007) explores participatory joint working, welfare state, social capacity, health inequalities, citizen involvement and community capacity. It captures the experiences of local community and front-line workers whilst delivering the Health Focus Group (HFG) in the NDC programme. Using action learning reflection techniques, the study analyses a purposeful sample of 15 from the local community, front-line workers, and strategic respondents involved in the NDC health programme. The research demonstrated the NDC did increase participation, joint working and involvement of local actors 1998–2003. The importance of communication, leadership and relationships was recognised as an important catalyst for developing community governance models. The new action learning spaces initiated, designed and delivered 19 new models of joint local clinical, community and complementary health and well-being projects. In 2001, New Labour introduced public private finance initiatives with the Primary Care Trust (PCT) which conflicted with the local actors’ involvement in the participatory joint decision-making. The reconfiguration of health and social care services and the new public health models introduced complex governance and monitoring models, further distancing the local actors from the process. Strategic staff changes in key governance positions also adversely affected the communication and trust established with local actors. The research concluded operational, tactical, and strategic alignment is necessary to maximise joint participation in decision-making.
  • Public Policy Development and Implementation in the United Arab Emirates. A study of organizational learning during policy development and implementation in the Abu Dhabi Police and the United Arab Emirates Ministry of Interior

    Not named; Alghalban, Doaa F.H. (University of BradfordFaculty of Management and Law, 2017)
    This reflective analysis of the Emirati public policy process (PPP) cycle and implications of uneven application of new public management (NPM) paradigms in the UAE offers insight into the way that public administrations develop, learn, evolve, and cope with new challenges during the policy development process. The author also assesses the relationship between organizational learning and organizational practices, to generate practical knowledge and experience that is translated into recommendations that will benefit UAE government organizations, and indeed any public sector organization in the Gulf Region. Inside action research was chosen to emphasize the author's dual role as both a researcher and a participant. As an advisor to both the Ministry of the Interior (MOI) of the UAE and the Abu Dhabi Police (ADP), the author helped both organisations improve their PPP experiences while researching the challenges, learning, and adaptations which occurred while policy was being developed within the MOI. The author generated data through reflective memos, informal interviews, and document analysis, and presents her findings in terms of both academic findings and practice-oriented recommendations. The author primarily found that new models were necessary to reflect the highly flexible and authority-oriented UAE PPP cycle. The author also explored how cultural understandings led to challenges with NPM and learning in the UAE public administration, hindering policy development. Finally, the author found that her own position, as a female expatriate in the Emirati government, allowed for some valuable reflection about experience of serving in a Global South public administration.
  • Behaviour of continuous concrete beams reinforced with hybrid GFRP/steel bars

    Ashour, Ashraf F.; Lam, Dennis; Araba, Almahdi M.A.A. (University of BradfordFaculty of Engineering and Informatics, 2017)
    An investigation on the application of hybrid glass fibre reinforced polymer (GFRP) and steel bars bars as longitudinal reinforcement for simple and continuous concrete beams is presented. Three simply and eleven multi-spans continuous reinforced concrete beams were constructed and tested to failure. Nine continuous and two simply supported beams were reinforced with a hybrid combination of both GFRP and steel re-bars at mid spans and internal support regions. In addition, two continuous concrete beams reinforced with either GFRP or steel bars and one simply supported beam reinforced with GFRP bars were tested as control beams. The beams were classified into two groups according to the reinforcement configurations. All specimens tested were 200 mm in width and 300 mm in depth. The continuous beams comprised of two equal spans, each of 2600 mm, while the simply supported beams had a span of 2600 mm. Unlike GFRP reinforced concrete beams, the hybrid and steel reinforced concrete beams failed in a favourable ductile manner and demonstrated narrow cracks and smaller deflections compared to the GFRP-reinforced control beam. The lower stiffness and higher deflection of GFRP reinforced concrete beams can be controlled and improved by the use of steel reinforcement in combination with GFRP re-bars. However, the ratio of GFRP to steel reinforcement is a key factor to ensure sufficient ductility and stiffness beyond the first cracking stage. The experimental results showed that the extent of moment redistribution in hybrid reinforced continuous beams depends mainly on the amount of hybrid reinforcement ratio in critical sections. Similar area of steel and GFRP bars in critical sections leads to limited moment redistribution whereas different amount of steel and FRP bars in critical sections leads to a remarkable moment redistribution. Design guidelines and formulas have been validated against experimental results of hybrid GFRP/steel reinforced concrete beams tested. The Yoon’s equation reasonably predicted the deflections of the hybrid beams tested whereas Qu’s model which is based on ACI 440.1R-15 underestimated the deflections of hybrid beams tested at all stage of loading after cracking. The ACI 440.2R-08 and Pang et al., (2015) equations reasonably predicted the sagging failure moment in most continuous hybrid reinforced concrete beams, whereas they underestimated the hogging flexural strength at failure of most hybrid continuous beams. On the other hand, the formulas proposed by Yinghao et al., (2013) was very conservative in predicting the failure moment at the critical sagging and hogging sections. On the analytical side, a numerical technique consisting of sectional analyses has been developed to predict the moment–curvature relationship and moment capacity of hybrid FRP/ steel reinforced concrete members. The numerical technique has been validated against the experimental test results obtained from the current research and those reported in the literature. In addition, a two-dimensional nonlinear finite element model was proposed using ABAQUS package. The proposed model was validated against the experimental results of the beams tested in the present research.
  • Embodiment and its Effects. How Creativity, Perception and Sensory Processing Sensitivity Link with Empathy and Theory of Mind Mechanisms

    Lesk, Valerie E.; Comerford Boyes, Louise; Kiou, Jade L. (University of BradfordDivision of Psychology, Faculty of Social Sciences, 2018)
    Embodied cognition is the study of how actions and interactions with objects and individuals affect cognitive processing. Neuroaesthetics deals with the neural, biological and evolutionary aspects of aesthetic experience which occur through the senses and consist of the emotional value placed onto objects, for example the appreciation of art work, dance, or music. These are individual and differ depending on level of expertise and experience within the art. The main aim of the thesis was to investigate the link between embodiment and aesthetics through examining people’s level of creativity, colour perception and sensory processing sensitivity (SPS) in relation to levels of empathy and theory of mind (ToM). Research into this is sparse as the role of the body in relation to aesthetic experiences is a relatively new concept. Preference for portraits versus landscapes was also investigated to look at any role of social stimuli in aesthetic preference. Results demonstrate that participants with (i) higher levels of creativity (for some types of creativity) and (ii) more acute colour perception had higher levels of empathy/ToM. Individuals who had higher SPS demonstrated higher empathy/ToM. It was also found that colour perception and empathy levels decrease with age, and aesthetic preference for portraits increase with age. These results have implications for education/schools, the prison service, for specific clinical conditions such as autism, Parkinson’s disease, schizophrenia, and attention deficit/hyperactivity disorder, particularly given the role of dopamine in these disorders and in colour perception. Future research should investigate these findings using brain imaging and physiological measures.
  • A Hybrid Multibiometric System for Personal Identification Based on Face and Iris Traits. The Development of an automated computer system for the identification of humans by integrating facial and iris features using Localization, Feature Extraction, Handcrafted and Deep learning Techniques.

    Qahwaji, Rami S.R.; Ipson, Stanley S.; Nassar, Alaa S.N. (University of BradfordSchool of Electrical Engineering and Computer Science, 2018)
    Multimodal biometric systems have been widely applied in many real-world applications due to its ability to deal with a number of significant limitations of unimodal biometric systems, including sensitivity to noise, population coverage, intra-class variability, non-universality, and vulnerability to spoofing. This PhD thesis is focused on the combination of both the face and the left and right irises, in a unified hybrid multimodal biometric identification system using different fusion approaches at the score and rank level. Firstly, the facial features are extracted using a novel multimodal local feature extraction approach, termed as the Curvelet-Fractal approach, which based on merging the advantages of the Curvelet transform with Fractal dimension. Secondly, a novel framework based on merging the advantages of the local handcrafted feature descriptors with the deep learning approaches is proposed, Multimodal Deep Face Recognition (MDFR) framework, to address the face recognition problem in unconstrained conditions. Thirdly, an efficient deep learning system is employed, termed as IrisConvNet, whose architecture is based on a combination of Convolutional Neural Network (CNN) and Softmax classifier to extract discriminative features from an iris image. Finally, The performance of the unimodal and multimodal systems has been evaluated by conducting a number of extensive experiments on large-scale unimodal databases: FERET, CAS-PEAL-R1, LFW, CASIA-Iris-V1, CASIA-Iris-V3 Interval, MMU1 and IITD and MMU1, and SDUMLA-HMT multimodal dataset. The results obtained have demonstrated the superiority of the proposed systems compared to the previous works by achieving new state-of-the-art recognition rates on all the employed datasets with less time required to recognize the person’s identity.Multimodal biometric systems have been widely applied in many real-world applications due to its ability to deal with a number of significant limitations of unimodal biometric systems, including sensitivity to noise, population coverage, intra-class variability, non-universality, and vulnerability to spoofing. This PhD thesis is focused on the combination of both the face and the left and right irises, in a unified hybrid multimodal biometric identification system using different fusion approaches at the score and rank level. Firstly, the facial features are extracted using a novel multimodal local feature extraction approach, termed as the Curvelet-Fractal approach, which based on merging the advantages of the Curvelet transform with Fractal dimension. Secondly, a novel framework based on merging the advantages of the local handcrafted feature descriptors with the deep learning approaches is proposed, Multimodal Deep Face Recognition (MDFR) framework, to address the face recognition problem in unconstrained conditions. Thirdly, an efficient deep learning system is employed, termed as IrisConvNet, whose architecture is based on a combination of Convolutional Neural Network (CNN) and Softmax classifier to extract discriminative features from an iris image. Finally, The performance of the unimodal and multimodal systems has been evaluated by conducting a number of extensive experiments on large-scale unimodal databases: FERET, CAS-PEAL-R1, LFW, CASIA-Iris-V1, CASIA-Iris-V3 Interval, MMU1 and IITD and MMU1, and SDUMLA-HMT multimodal dataset. The results obtained have demonstrated the superiority of the proposed systems compared to the previous works by achieving new state-of-the-art recognition rates on all the employed datasets with less time required to recognize the person’s identity.
  • The Turkish Model, the Double-Security Dilemma, and the Political Reproduction of State Polities in the Middle East

    Shahi, Afshin; Morvaridi, Behrooz; Araj, Victoria D. (University of BradfordFaculty of Management, Law and Social Sciences, 2018)
    Conceptually the aims of this thesis are to show the salient features of the political reproduction of states as a necessity for their survival as they continually face a double-security dilemma in the neoliberal era. Empirically this thesis examines Turkey’s ruling party from 2002 to 2015. The Justice and Development Party (Adalet ve Kalkınma Partisi, AKP) maintained authority by mitigating the polities and actors that posed vertical and horizontal competition to their power (the double-security dilemma of domestic and international threats faced by state rulers). To outcompete and absorb its rivals, the AKP maintained a post-Islamist alliance-building model of political reproduction through a globalized Islamic neoliberal authority pattern until 2011. This became popularized as the ‘Turkish Model’, a model of political reproduction framed as suitable for other Muslim-majority states. The findings from data analysis show that to maintain the constitutive sovereignty of the Turkish state, the AKP built a post-Islamist hegemony. Furthermore, this thesis explores how the AKP horizontally built a pluralist vision of neo-ottomanism enabling their navigation of the international political system. Their ‘zero-problems’ foreign policy was the cornerstone of building regional liberal peace. This policy was the basis of the AKP’s maintenance of functional sovereignty until the ‘Arab Spring’. Yet, the new double-security dilemma that emerged through the ‘Arab Spring’ not only threatened the existence of post-Islamism within Turkey, but the existence of the ‘Turkish Model’ itself. The AKP then moved towards a fortifying pattern of authority to shield both themselves and the Republic from emergent threats
  • Impact of combined microprocessor control of the prosthetic knee and ankle on gait termination in unilateral trans-femoral amputees. Limb mechanical work performed on centre of mass to terminate gait on a declined surface using linx prosthetic device

    Buckley, John G.; Abdulhasan, Zahraa M. (University of BradfordDivision of Biomedical Engineering, School of Engineering, 2018)
    The major objective of this thesis was to investigate how the use of a recently developed microprocessor-controlled limb system altered the negative mechanical work done by the intact and prosthetic limb when trans-femoral amputees terminated gait. Participants terminated gait on a level surface from their self-selected walking speed and on declined surface from slow and customary speeds, using limb system prosthesis with microprocessor active or inactive. Limb negative work, determined as the integral of the negative mechanical (external) limb power during the braking phase, was compared across surface, speed and microprocessor conditions. Halting gait was achieved predominantly from negative work done by the trailing/intact. Trailing versus leading limb mechanical work imbalance was similar to how able body individuals halted gait. Importantly, the negative limb work performed on the prosthetic side when terminating gait on declined surface was increased when the microprocessor was active for both slow and customary speeds (no difference on level surface) but no change on intact limb. This indicates the limb system’s ‘ramp-descent mode’ effectively/dynamically altered the hydraulic resistances at the respective joints with evidence indicating changes at the ankle were the key factor for increasing the prosthetic limb negative work contribution. Findings suggest that trans-femoral amputees became more assured using their prosthetic limb to arrest body centre of mass velocity when the limb system’s microprocessor was active. More generally findings suggest, trans-femoral amputees should obtain clinically significant biomechanical benefits from using a limb system prosthesis for locomotion involving adapting to their everyday walking where adaptations to an endlessly changing environment are required.
  • The Role of Intangible Human Factors in Business Success in South Asian Ethnic Minority Small Businesses

    Harding, Nancy H.; Williams, Jannine; Cornelius, Nelarine; Wallace, James; Haq, Muhibul (University of BradfordFaculty of Management and Law, 2016)
    Extant scholarship has paid considerable attention to exploring the impact of people-dependent intangible resources on business success but in large organisations only. Research about the role of these resources in small businesses, in general, and in ethnic minority small businesses, in particular, is scarce. The current study attempts to narrow this gap. Since it is impossible to study all the ethnic minority small businesses, this study uses a case study strategy that focuses on South Asian ethnic minority small businesses that deal in fashion. The study adopts a qualitative research methodology, it uses the semi-structured in-depth interview method to collect data, and it espouses an inductive thematic technique for coding/analysis of the data. Five overarching themes emerged from the interview data. These are: business success; compassionate customer service; relationships; knowledge, experience, training and education; and ethnic culture and the wider economic and political environment. Discussion of these themes leads to the formation of the culture-induced entrepreneurship model. According to this model, the continued success of these businesses is driven by the ethnic culture, while the existence of these businesses helps to maintain the culture in return. However, overdependence on the coethnic base might risk the future success of these businesses. This thesis concludes by highlighting its theoretical contributions to the culturalist view and the mixed embeddedness model of ethnic minority entrepreneurship and small business literature. The implications of this study for researchers, practitioners, and policy-makers, as well as its limitations and the possible future research paths, are also discussed.
  • The role of photoreceptors in human skin physiology; potential targets for light-based wound healing treatments. Identification of opsins and cryptochromes and the effect of photobiomodulation on human skin and in cultured primary epidermal keratinocytes and dermal fibroblasts

    Thornton, M. Julie; Botchkarev, Vladimir A.; Castellano-Pellicena, Irene (University of BradfordCentre for Skin Sciences, Faculty of Life Sciences, 2017)
    The positive effect of photobiomodulation in wound healing has previously been reported, however there is a considerable lack of knowledge regarding the molecular mechanisms involved, and no consensus on light parameters. Cytochrome c oxidase (CCO) is established as the main photoreceptor in cells, but light also induces nitric oxide (NO), production of reactive oxygen species (ROS) and activation of ion channels. Emerging new molecular targets include the GPCRs opsins (OPNs) and the circadian clock transcription factors, cryptochromes (CRYs). Localisation of OPN1-SW, OPN3, OPN5, CRY1 and CRY2 was seen in female facial and abdominal human skin. Furthermore, expression of these photoreceptors was retained in primary epidermal keratinocytes and dermal fibroblasts in culture; both cell types expressed OPN1-SW, OPN3, CRY1 and CRY2, at the mRNA and protein level. OPN2 was only expressed in cultured dermal fibroblasts, while in line with in situ expression, OPN5 was only expressed in cultured keratinocytes. The photoreceptor-expressing cultured epidermal keratinocytes demonstrated a dose- and wavelength- dependent response in both metabolic activity and cell migration in a scratch-wound assay. Specifically, low dose (2 J/cm2) blue light (447 nm) increased metabolic activity, but it did not impact keratinocyte migration. In contrast, high dose (30 J/cm2) blue light had no effect on metabolism, but inhibited migration of epidermal keratinocytes. Red light (655 nm) at 30 J/cm2 stimulated metabolic activity but did not modulate migration, while a higher dose of 60 J/cm2 had no effect on keratinocyte metabolic activity. In order to study OPN3 and CRY1 function, they were silenced in keratinocytes using siRNA; additionally 8 μM KL001 was used to stabilize CRY1. KL001 inhibited migration, and induced KRT1 and KRT10, an effect which was abrogated by knockdown of OPN3. Interestingly, knockdown of OPN3 upregulated CRY1 expression, while KL001 upregulated OPN3 expression, indicating a regulation by OPN3 of the molecular epidermal clock. Low levels of blue light increased early differentiation of epidermal keratinocytes, which was mediated by OPN3 and circadian clock mechanisms. However, low levels of blue light decreased keratinocyte DNA synthesis, which was mediated by circadian clock independently of OPN3. Translation of parameters ex vivo showed increasing re-epithelialisation and induction of OPN3 and CRY1 expression following exposure to 2 J/cm2 of blue light; however high doses of blue light inhibited re-epithelialisation. Red light, also increased re-epithelialisation, but had no effect on OPN3 or CRY1 expression. In conclusion, photoreceptors are expressed in human skin and they mediate DNA synthesis, migration and differentiation of epidermal keratinocytes. Furthermore, low dose of blue light interacts with OPN3 to induce epidermal differentiation, through the regulation of the circadian clock. A better understanding of the molecular mechanisms behind the photobiomodulation response in vitro will help to develop light based therapies for human wound healing. Interestingly, selected light parameters translated to human ex vivo skin showed a beneficial effect of low doses of blue (2 J/cm2) and red (30 J/cm2) light in re-epithelialisation.
  • Functional Investigation of Dual αvβ3 and αllbβ3 Integrin Inhibition in Haematological and Solid Tumour Models

    Sheldrake, Helen M.; Patterson, Laurence H.; Elsharif, Amal A.M. (University of BradfordInstitute of Cancer Therapeutics, Faculty of Life Sciences, 2018)
    Invasion and metastasis of cancer is the leading cause of increased mortality. In addition, haematological malignancies (leukaemia and lymphoma) are a significant cause of morbidity and mortality in both children and adults. Therefore, new treatments which will inhibit cancer progression are required. Integrin adhesion receptors, particularly the RGD-binding integrin subfamily comprising αvβ3, αvβ5, αvβ6, αvβ8, αllbβ3, α5β1, α8β1 and αvβ1 are related to progress and spread of cancer and poor prognosis. Because of the importance of integrin biology in the regulation of cancer dissemination, the integrin receptors are being utilised as targets to regulate cancer progression. The goal of this study was to develop a dual αvβ3/ αIIbβ3 expressing model for testing integrin antagonists. Expression of αv, αIIb, and β3 integrin subunits was characterised using immunofluorescence and flow cytometry in a panel of cell lines. After characterising the expression of αv, αIIb and β3 integrin subunits in inducible and natural expression models (K562 and MCF-7 cells respectively), functional tests for cellular adhesion, detachment and migration were determined. Phorbol 12-myristate 13-acetate (PMA)-treated K562 cells showed increased adhesion on fibrinogen compared to untreated cells. Adhesion of cancer cells (K562 ± PMA and MCF-7) to fibrinogen was inhibited and detachment was induced by the known β3 antagonists, cRGDfV and GR104453. Migration of cancer cells (K562 without PMA and MCF-7) was inhibited by combination of the known β3 antagonists. A panel of 12 novel small molecules developed in the ICT was investigated for cytotoxicity and activity in the validated function assays. ICT9055 was the most potent antagonist in inhibition of cell adhesion, migration, and inducing cell detachment. The data presented in this thesis had selected models and assays for evaluating small molecule integrin antagonists and identified ICT9055 as a promising molecule to develop for further preclinical evaluation.
  • Molecular interactions in pharmaceutical preformulation and supramolecular complexes. Structural properties governing drug-plasma protein binding and investigation of amino acids co-crystals

    Paradkar, Anant R.; Liu, Xiangli; Kamble, Sharad R. (University of BradfordSchool of Biomedical Sciences and Pharmacy, Faculty of Life Sciences, 2018)
    The study of pharmaceutical preformulation includes the evaluation of pharmacokinetic, pharmacodynamic and physicochemical properties of the drug molecules that aid the formulation. However, it has a limited role in determining drug dosage optimisation in the formulation. The study of drug-Plasma Protein Binding (PPB), and the lipophilicity, solubility, and ionic behaviours of the desired drug molecules addresses the gap and enhances our undertraining related to the behaviour of the drug molecules in the body. The High-Performance Liquid Chromatography (HPLC) technique was used in the current study to assess drug-PPB interaction. Using Michael Abraham’s ‘Linear Free Energy Relationship’ (LFER) method, two major plasma proteins namely, Human Serum Albumin as HSA and α-1-Acid Glycoprotein as AGP, were used and the structural properties governing drug-plasma protein binding was determined. This is the first time that the effect of ionised species on PPB has been quantitatively evaluated. In addition, the molecular interactions also play a key role in the supramolecular complexes of co-crystals. The project also evaluated the co-crystallisation process and its effect on physicochemical properties of the drug. In the current study, amino acids (AAs) have been observed to be a prominent source of coformers. The AAs showed co-crystals formation with carboxylic acids, nonsteroidal anti-inflammatory drug (NSAID) and citric acid which overcome the hygroscopicity problems and improved the physical stability issues during storage. This study has also identified a new formulation which is helpful for improvement in the stability of effervescent tablets at various relative humidity (RH) conditions which will reduce the manufacturing cost associated with the production of effervescent tablets.
  • Punching shear of concrete flat slabs reinforced with fibre reinforced polymer bars

    Ashour, Ashraf F.; Lam, Dennis; Sheehan, Therese; Al Ajami, Abdulhamid (University of BradfordFaculty of Engineering and Informatics, 2018)
    Fibre reinforcement polymers (FRP) are non-corrodible materials used instead of conventional steel and have been approved to be an effective way to overcome corrosion problems. FRP, in most cases, can have a higher tensile strength, but a lower tensile modulus of elasticity compared to that of conventional steel bars. This study aimed to examine flat slab specimens reinforced with glass fibre reinforced polymer (GFRP) and steel bar materials for punching shear behaviour. Six full-scale two-way slab specimens were constructed and tested under concentric load up to failure. One of the main objectives is to study the effect of reinforcement spacing with the same reinforcement ratio on the punching shear strength. In addition, two other parameters were considered, namely, slab depth, and compressive strength of concrete. The punching shear provisions of two code of practises CSA S806 (Canadian Standards 2012) and JSCE (JSCE et al. 1997) reasonably predicted the load capacity of GFRP reinforced concrete flat slab, whereas, ACI 440 (ACI Committee 440 2015) showed very conservative load capacity prediction. On the other hand, a dynamic explicit solver in nonlinear finite element (FE) modelling is used to analyse a connection of column to concrete flat slabs reinforced with GFRP bars in terms of ultimate punching load. All FE modelling was performed in 3D with the appropriate adoption of element size and mesh. The numerical and experimental results were compared in order to evaluate the developed FE, aiming to predict the behaviour of punching shear in the concrete flat slab. In addition, a parametric study was created to explore the behaviour of GFRP reinforced concrete flat slab with three parameters, namely, concrete strength, shear load perimeter to effective depth ratio, and, flexural reinforcement ratio. It was concluded that the developed models could accurately capture the behaviour of GFRP reinforced concrete flat slabs subjected to a concentrated load. Artificial Neural Networks (ANN) is used in this research to predict punching shear strength, and the results were shown to match more closely with the experimental results. A parametric study was performed to investigate the effects of five parameters on punching shear capacity of GFRP reinforced concrete flat slab. The parametric investigation revealed that the effective depth has the most substantial impact on the load carrying capacity of the punching shear followed by reinforcement ratio, column perimeter, the compressive strength of the concrete, and, the elastic modulus of the reinforcement.
  • Hybrid Modelling and Optimisation of Oil Well Drillstrings

    Bryant, David; Li, Jian-Ping; Rahmanian, Nejat; Alkaragoolee, Mohammed Y.A. (University of BradfordFaculty of Engineering and Informatics, 2018)
    The failure of oil well drillstrings due to torsional and longitudinal stresses caused by stick-slip phenomena during the drilling operation causes great expense to industry. Due to the complicated and harsh drilling environment, modelling of the drillstring becomes an essential requirement in studies. Currently, this is achieved by modelling the drillstring as a torsional lumped model (which ignores the length of the drillstring) for real-time measurement and control. In this thesis, a distributed-lumped model including the effects of drillstring length was developed to represent the drillstring, and was used to simulate stick-slip vibration. The model was developed with increasing levels of detail and the resultant models were validated against typical measured signals from the published literature. The stick-slip model describes the friction model that exists between the cutting tool and the rock. Based on theoretical analysis and mathematical formulation an efficient and adaptable model was created which was then used in the application of a method of species conserving genetic algorithm (SCGA) to optimise the drilling parameters. In conclusion, it was shown that the distributed-lumped model showed improved detail in predicting the transient response and demonstrated the importance of including the drillstring length. Predicting the response of different parameters along the drillstring is now possible and this showed the significant effect of modelling the drillcollar. The model was shown to better represent real system and was therefore far more suited to use with real time measurements.
  • A Mixed Methods Study Investigating the Community Pharmacist’s Role in Palliative Care

    Morgan, Julie; Blenkinsopp, Alison; Miller, Elizabeth J. (University of BradfordSchool of Pharmacy and Medical Sciences, Faculty of Life Sciences, 2017)
    There is little research investigating factors that facilitate or inhibit timely access to palliative care medicines from community pharmacies. Though palliative care is recognised within the UK government’s strategy and community pharmacists are considered to have a role it is uncertain to what extent this aim is incorporated into local practice. This thesis uses mixed methods to investigate the time taken to access palliative care medication from five community pharmacies in one area of England. The effect of prescription errors, stock availability and other factors is examined. Furthermore, semi-structured interviews with five community pharmacists and eleven other healthcare professionals explore medication access and the community pharmacist’s role in palliative care using the Framework method. Stock availability led to delays with one in five customers going to more than one pharmacy to get urgently required palliative care medications. Legal prescription errors were more common on computer generated prescriptions but did not lead to delays. Three subthemes were identified in accessing palliative care medicines: environment and resources; communication and collaboration; skills and knowledge. The community pharmacist’s role in palliative care was limited due to reluctance from other healthcare professionals to share information, poor access to patient records and lack of integration into the primary healthcare team. This study highlights implications for professionals, commissioners and providers to improve services for those trying to access palliative medication. Community pharmacies remain a largely untapped resource for supporting patients, relatives and carers towards the end of life in both cancer and other advanced life-limiting diseases.
  • The Role of Polycomb Repressive Complex 2 in Epidermal Homeostasis and Hair Growth

    Botchkareva, Natalia V.; Mardaryev, Andrei N.; Asamaowei, Inemo E. (University of BradfordFaculty of Life Sciences, 2017)
    Polycomb repressive complex 2 (PRC2) catalyses the methylation of ‘Lys-27’ of histone H3, leading to transcriptional repression of target genes through its catalytic subunit Enhancer of zeste homolog 1/2 (EZH1/2). PRC2 functions as a critical regulator of stem cells in mouse embryonic and adult tissues. However, the role of PRC2 in human skin remains largely unknown. This study investigated the role of PRC2 in human epidermal homeostasis and hair growth. The expression of EZH2 was elevated in differentiating suprabasal layers of the human epidermis. Consistently, EZH1/2 expression and enzymatic activity was upregulated in differentiating primary human keratinocytes (NHEKs) in vitro. Inhibition of EZH2 and Embryonic ectoderm development (EED) in NHEKs stimulated the expression of differentiation-associated genes, therefore leading to their premature differentiation; while inhibition of EZH1/2 reduced cell proliferation and promoted apoptosis. Silencing of EZH2 in NHEKs induced complex changes in gene expression programmes, including the upregulation of terminal differentiation genes, such as Filaggrin. EZH2 expression was downregulated in aged keratinocytes accompanied with upregulation of senescence-associated genes, p16INK4A and p19INK4D, suggesting EZH2 involvement in epidermal aging. In human anagen hair follicle (HF), EZH2 was detected in stem and progenitor cells; and hair matrix keratinocytes. Silencing EZH2 in HFs accelerated anagen-catagen transition and retarded hair growth accompanied by decreased proliferation and increased apoptosis. Silencing EZH2 in outer root sheath keratinocytes resulted in upregulation of p14ARF and K15, suggesting EZH2 involvement in regulating proliferation and stem cell activity. Thus, this study demonstrates that PRC2-mediated repression is crucial for epidermal homeostasis and hair growth. Modulating the activities of PRC2 in skin might offer a new therapeutic approach for disorders of epidermal differentiation and hair growth.
  • An examination into the quality of regional trade institutions: The economic community of West African states (ECOWAS); a historical, theoretical and modelling perspective

    Jackson, Karen; Potts, David J.; Bah, Essa (University of BradfordDivision of Economics, Faculty of Social Science, 2017)
    This thesis examines the determinants of institutional quality and the process of convergence in the ECOWAS in order to inform policy about the region’s deep integration scheme. The first part of the thesis examines the historical changes that took place in the development of common institutions in West Africa in the pre-independence era. The findings demonstrated that the region exhibited some common institutions, including common currencies, standardised trade rules and protection of trade routes which facilitated regional and international trade. A single administration system helped in the effective implementation of the common institutions. Therefore, historical changes after independence led to the loss of some facets of these common institutions in West Africa. The second part examined determinants of institutional quality and the process of convergence using econometric analysis. The findings demonstrated that the process of convergence could be accelerated if WAMZ and WAEMU work together as one monetary zone under ECOWAS. Moreover, the findings also demonstrated that the level of development, state capacity, FDI, regional trade, history and regional trade partners institutional quality contain useful information in explaining the quality of institutions today. Therefore, ECOWAS’s deep integration goal would require improving some of these factors in order to facilitate the process of developing common institutions and improve their quality. In the long term, a single administration system akin to the colonial era and the Empires of Western Sudan would be desirable. This will require political commitment to do so. ECOWAS members should have the confidence that deep integration is feasible given that it existed in the region in the past.
  • The Impact of Oil Revenue on the Iranian Economy

    Jalilian, Hossein; Morvaridi, Behrooz; Olfati, Ronak (University of BradfordFaculty of Social Sciences, 2018)
    This study aims to identify the effects of oil income on economic growth in Iran over the period 1955-2014. The empirical literature indicates that countries with natural resources are growing more slowly than their counterparts. However, the results from this literature are far from conclusive, particularly in regard to the role played by oil-rich countries. Needless to say, this role depends on other factors as well, including the political situation in the country, the quality of institutions, and the efficacy of the financial system. Some empirical research has found that natural resources, particularly oil, can have a positive impact on the output of a country. although natural resources are not a factor of production in growth theories, studies have used different growth frameworks in order to discover whether having natural resources is a blessing or a curse. In line with recent studies, this work uses an augmented neoclassical growth model to develop a theoretical framework where oil enters the long-term output of the country through saving and investment. Overall, the results suggests that oil income has a positive impact on the level of output per capita in Iran. The findings of the econometric results are in line with the historical analysis of the study. Since different methods and proxies were used, a total of eight models were estimated. Interestingly, when PRIVY is used as an index of financial development, the result of the study changes and oil no longer has a significant impact on the economy. However, this can be translated to an inefficient allocation of credit to the private sector.

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