Now showing items 21-40 of 1443

    • Towards A Practice Theory of Goal-setting: Assessing the theoretical goal-setting of The Leprosy Mission in Nigeria

      Kellehear, Allan; McIntosh, Bryan; McNamara, Barbara; Ogbeiwi, Osahon J.I. (University of BradfordFaculty of Health Studies, 2019)
      Goal-setting is indispensable for effective healthcare management. Yet, literature evidence suggests many organisations worldwide do not know how to formulate ‘SMART’ goals. Evidence of how existing theories work in practice is scarce, and the practices in low-income countries are unknown. Therefore, this research explored how leprosy project goals were formulated to describe the theoretical practice framework of The Leprosy Mission Nigeria (TLMN). Using a case-study design, ten managers were interviewed individually concerning their goal-setting knowledge, experience and perspective; and documented goals of six projects were reviewed. A five-step constructionist thematic data analysis generated eleven theoretical frameworks from the concepts of the emergent core themes of ‘stakeholders’, ‘strategies’ and ‘statements.’ Further theorisation reduced them to one general framework. This revealed TLMN’s goal-setting practice as a four-stage centre-led, top-down, beneficiary-focused and problem-based process. The stages were national preparation, baseline needs-survey, centralised goal formulation and nationalised planning. The outcome was the formulation of assigned, ‘non SMART’ objective statements, which are then used for planning projects. Other theoretical models constructed included a Goal Effects Cycle, ‘SMARTA’ goal attributes and hierarchical criteria for differentiating goal-types. A theory developed from TLMN goal-setting postulates that: ‘Assigned non SMART goal formulation directly results from centralised goal-setting practice and is the predictor of unrealistic project planning.’ Therefore, I propose that goal statements will be ‘SMARTA’ and plans, more realistic and relevant if goal setting is done collaboratively by all stakeholders at all stages of the process. Also, ‘Change-Beneficiary-Indicator-Target-Timeframe’ and ‘Change- Beneficiary-Location-Timeframe’ frameworks are recommended as templates for writing SMART objectives and aims respectively.
    • Investigating the expression and function of aldehyde dehydrogenases in prostate cancer. Probing the expression and function of ALDHs using chemical probes, drugs and siRNA

      Pors, Klaus; Maitland, N.J.; Phillips, Roger M.; Sadiq, Maria (University of BradfordFaculty of Life Sciences, 2017)
      Castration-resistant prostate cancer (CRPC) remains an aggressive incurable disease in men mainly due to treatment resistance. Current treatments do not effectively eradicate cancer stem cells (CSCs), which play a pivotal role in tumour maintenance, progression and drug resistance. Aldehyde dehydrogenases (ALDHs) have been used in some tumour types as CSC markers. Their high expression and high functional activity found in CSCs is also associated with drug resistance. Emerging evidence suggests deregulation of certain ALDH isoforms have implications in cancer. The role of ALDHs in prostate cancer as potential biomarkers and therapeutic targets has not been fully explored yet. Accordingly, this study investigated the expression, regulation and function of selected ALDH isoforms in prostate cancer. This study showed that ALDH1A3, ALDH1B1, ALDH2 and ALDH7A1 are highly expressed in primary prostate cancer cells (n=9) compared to benign (n=9) prostate cells. The expression of ALDH1A3 was high in the stem cells (SCs) (n=3) as well as the more differentiated counterparts (n=16). Treatment of both benign and malignant primary prostate cancer cells with all-trans retinoic acid (atRA) also resulted in increased expression of ALDH1A3 and ALDH3A1, supporting a feedback loop between atRA and ALDHs. Furthermore, SerBob, Bob and LNCaP cells were sensitive to treatment with epigenetic drugs and led to significantly higher expression of ALDH1A2, ALDH3A1 and ALDH7A1 respectively. Importantly, siRNA suppression of ALDH1A3 and ALDH7A1 led to reduced SC properties of primary prostate cultures including reduced cell viability, migration and colony formation, and increased differentiation of transit amplifying (TA) cells to committed basal (CB) cells. Novel ALDH-affinic probes showed reduced cell viability of primary prostate epithelial cultures as a single agent and also when used in combination with docetaxel. The results indicate the potential of using ALDH-affinic compounds as single agents for therapeutic intervention or in combination with docetaxel to sensitise resistant cells to this anticancer drug. The data in this thesis provides novel findings, which supports ALDH1A2, -1A3 and -7A1 as potential biomarkers and/or therapeutic targets for drug intervention. Although, a study analysing a larger number of samples is necessary to fully understand ALDH isoform expression in CSC, TA and CB cells it is envisaged that an ALDH-targeted therapy have potential in future treatment strategies for prostate cancer.
    • Engineering of Amorphous Active Pharmaceutical Ingredients by Sonoprecipitation and Spray Drying Pre-and Post-Processing Pharmaceutical Characterisation. Pre- and Post-Processing Physicochemical and Micromeritic Characterisation of Active Pharmaceutical Ingredients

      Paluch, Krzysztof J.; Paradkar, Anant R.; Abdalmaula, Hanan A.S. (University of BradfordSchool of Pharmacy and Medical Sciences. Faculty of Life Sciences, 2019)
      Amorphous active pharmaceutical ingredients remain in the research focus as an avenue to achieve a better solubility of drugs. Several processing techniques are applied to produce amorphous materials. Main two approaches applied to production of amorphous phases are comminution of crystalline materials in order to break down molecular long-range order of their crystal lattices and amorphous phase precipitation from solutions. This thesis is focused on processing challenges in preparation of amorphous API phases from solutions by spray drying and evaporative antisolvent sonoprecipitation. Budesonide (BUD) and simvastatin (SMV) were used as model poorly soluble APIs. Amorphous phases of relatively low-glass transition (Tg) APIs are physically unstable and crystallise upon storage and/or processing conditions. To tackle this issue, for the first time in this work a selection of polyvinylpyrrolidone vinyl acetate (PVP-VA) co-polymers has been applied to investigate impact of sonoprecipitation processing parameters and a composition of PVP-VA on physicochemical and micromeritic properties of BUD/PVP-VA nanoparticulate composites. Studies confirmed that in solid-state BUD is miscible with PVP-VA polymers. Application of factorial design revealed that processing parameters: polymer type, surfactant concentrations, time and amplitude of sonication impact the entrapment efficiency, drug loading, polydispersity and particle size properties of produced nanoparticles. The largest fraction of polymer to drug in produced nanoparticles has been achieved with PVP VA E-535. As it is known that polymer content in formulation of APIs may slow down its dissolution, novel approach to processing and dissolution enhancement of amorphous composites of SMV produced by spray drying has been applied. Introduction of easily crystallising inorganic salt- sodium chloride into spray drying feed rendered SMV-polyvinyl pyrrolidone (PVP) amorphous microparticles loaded with nanocrystalline NaCl. Addition of NaCl successfully facilitated generation of discrete microparticles post spray drying with low-Tg polymers, which otherwise were not processable as binary mixtures. In addition, NaCl content aided tabletability and dissolution of amorphous API composites with more viscous and high-Tg PVP polymers. Studies confirmed that application of factorial design facilitates robust design of production process of amorphous nanocomposites by sonoprecipitation as well as that introduction of soluble nanocrystalline phase into amorphous binary solid dispersion by spray drying aids its processing and dissolution.
    • A Study On Employee’s Intention To Adopt Green Practices At The Workplace In The Context Of The Hotel Industry

      Trivedi, Rohitkumar; Wang, Chengang; Fukukawa, Kyoko; Shahron, Syairah A.B. (University of BradfordFaculty of Management, Law and Social Sciences, 2019)
      This study aims to examine the effect of organisational commitment and employee’s pro-environmental behaviour at home on their intention to adopt green practices at the workplace in the context of hotel industry, by taking the theory of planned behaviour as a conceptual framework. Hotel employees play a critical role that affects customers' experiences, which then affects the overall hotel performance. However, the mechanism that affects their behavioural intention has yet to be investigated properly. Thus, a survey was conducted to collect the data from employees working in green and non-green hotels in Malaysia. Overall, there were 407 responses received, which represented a response rate of 55.75 percent. Then, a set of hypotheses was tested using the structural equation modelling. The empirical results indicate that organisational commitments have a positive effect on the attitude for engaging in a green behaviour and subjective norm, which in turn influenced employees’ intention to adopt green practices at work. Meanwhile, employees’ pro environmental behaviour at home has an indirect impact on employee’s intention to adopt green practices in the workplace through their attitude for engaging in a green behaviour, subjective norms, and perceived behavioural control. The findings lead to a theoretical contribution by incorporating another theory into the theory of planned behaviour, which is the social bond theory through organisational commitment and spill-over effect through pro environmental behaviour at home. Subsequently, a practical recommendation from this research is attainable to policy makers and hotel providers in order for them to understand and increase employees’ willingness to adopt green practices at the workplace.
    • Evaluating the ‘Success’ of The British Intervention in Sierra Leone 20 Years On: Implications for Sierra Leone, The UK, and Interventions Globally

      Harris, David; Scott, Lucy A. (University of BradfordFaculty of Management, Law and Social Sciences, 2022)
      Over the last two decades the frequency of humanitarian interventions in Africa, delivered by a wide range of actors, has increased. The British military intervention in the Sierra Leonean civil war in the early 2000s is often cited as an example of successful intervention and solidified Security Sector Reform (SSR) as a key component of state-building and development. Yet in-depth analysis of the long-term legacies of this ‘successful’ intervention are sparse and there remains a notable dearth in research exploring the British involvement from the perspectives of those directly involved or affected. This qualitative research provides a novel outlook by exploring micro-level experiences, thus addressing this lacuna through examining the legacies within Sierra Leone and in British foreign policy from an experiential perspective. The Responsibility to Protect (R2P) is used as a framework in order to draw out implications for global intervention practice, as arguably R2P must also be accompanied by a responsibility to fully understand the legacy of this social phenomenon. A themed analysis of original data explores the link between official narratives and the perspectives of those on the ground, often exposing a disconnect and identifying important nuances within the interpretation of the success of the British intervention. Through a critical analysis of these experiences significant questions are raised regarding the dynamics between intervening forces and the affected population; perceptions of legitimacy; accountability; and the implications for R2P more broadly.
    • Managing Workforce Diversity in Canada: An Empirical Study of the Factors Affecting the Adoption and Success of Diversity Strategies in Canadian Organisations

      Cornelius, Nelarine; Wallace, James; Haq, Rana (University of BradfordFaculty of Management, Law and Social Sciences, 2019)
      Equality, diversity and inclusion (EDI) in the workplace continues to be a dominant universal issue. Through its Employment Equity Act (EEA), Canada has acted as an exemplar in influencing equality legislation in other countries. The Canadian government’s thirtieth EEA annual report to Parliament presents a very positive picture of equality in employment for the four designated groups, DG: (women, Aboriginal peoples, persons with disabilities, and visible minorities) in the four industry sectors (Banking, Communication, Transportation, Other) federally regulated under the EEA’s legislated employment equity programme (LEEP). However, this claim of success is challenged in this study as specious in showing uniform take-up using aggregated LEEP data. A theoretical model is developed between variables representing external pressures, at the macro national level, internal pressures, at the meso-organisational level, and their hypothesized relationships with reactive and proactive EDI focused programmes pursued by LEEP organisations. This model is empirically validated by applying partial least squares structural equation path modelling to data collected from 440 LEEP organisations. Findings reveal that all four DGs are substantially under represented, relative to their labour market availability (LMA), in the majority of individual LEEP organisations, despite over three decades following EEA implementation. DG-LMA representation was also found to differ by industry sector. The main contribution to knowledge of this study is the introduction of a validated predictive EDI model developed and empirically validated for the four designated groups in the context of Canada. Applications of this generic model to other countries for benchmarking and comparative studies could contribute to EDI theory, practice and policy, internationally.
    • A smart sound fingerprinting system for monitoring elderly people living alone

      Kara-Zaitri, Chakib; El Hassan, Salem (University of BradfordFaculty of Engineering and Informatics, 2021)
      There is a sharp increase in the number of old people living alone throughout the world. More often than not, such people require continuous and immediate care and attention in their everyday lives, hence the need for round the clock monitoring, albeit in a respectful, dignified and non-intrusive way. For example, continuous care is required when they become frail and less active, and immediate attention is required when they fall or remain in the same position for a long time. To this extent, various monitoring technologies have been developed, yet there are major improvements still to be realised. Current technologies include indoor positioning systems (IPSs) and health monitoring systems. The former relies on defined configurations of various sensors to capture a person's position within a given space in real-time. The functionality of the sensors varies depending on receiving appropriate data using WiFi, radio frequency identification (RFIO), ultrawide band (UWB), dead reckoning (OR), infrared indoor (IR), Bluetooth (BLE), acoustic signal, visible light detection, and sound signal monitoring. The systems use various algorithms to capture proximity, location detection, time of arrival, time difference of arrival angle, and received signal strength data. Health monitoring technologies capture important health data using accelerometers and gyroscope sensors. In some studies, audio fingerprinting has been used to detect indoor environment sound variation and have largely been based on recognising TV sound and songs. This has been achieved using various staging methods, including pre-processing, framing, windowing, time/frequency domain feature extraction, and post-processing. Time/frequency domain feature extraction tools used include Fourier Transforms (FTs}, Modified Discrete Cosine Transform (MDCT}, Principal Component Analysis (PCA), Mel-Frequency Cepstrum Coefficients (MFCCs), Constant Q Transform (CQT}, Local Energy centroid (LEC), and Wavelet transform. Artificial intelligence (Al) and probabilistic algorithms have also been used in IPSs to classify and predict different activities, with interesting applications in healthcare monitoring. Several tools have been applied in IPSs and audio fingerprinting. They include Radial Basis Kernel (RBF), Support Vector Machine (SVM), Decision Trees (DTs), Hidden Markov Models (HMMs), Na'ive Bayes (NB), Gaussian Mixture Modelling (GMM), Clustering algorithms, Artificial Neural Networks (ANNs), and Deep Learning (DL). Despite all these attempts, there is still a major gap for a completely non-intrusive system capable of monitoring what an elderly person living alone is doing, where and for how long, and providing a quick traffic-like risk score prompting, therefore immediate action or otherwise. In this thesis, a cost-effective and completely non-intrusive indoor positioning and activity-monitoring system for elderly people living alone has been developed, tested and validated in a typical residential living space. The proposed system works based on five phases: (1)Set-up phase that defines the typical activities of daily living (TADLs). (2)Configuration phase that optimises the implementation of the required sensors in exemplar flat No.1. (3)Learning phase whereby sounds and position data of the TADLs are collected and stored in a fingerprint reference data set. (4)Listening phase whereby real-time data is collected and compared against the reference data set to provide information as to what a person is doing, when, and for how long. (5)Alert phase whereby a health frailty score varying between O unwell to 10 healthy is generated in real-time. Two typical but different residential flats (referred to here are Flats No.1 and 2) are used in the study. The system is implemented in the bathroom, living room, and bedroom of flat No.1, which includes various floor types (carpet, tiles, laminate) to distinguish between various sounds generated upon walking on such floors. The data captured during the Learning Phase yields the reference data set and includes position and sound fingerprints. The latter is generated from tests of recording a specific TADL, thus providing time and frequency-based extracted features, frequency peak magnitude (FPM), Zero Crossing Rate (ZCR), and Root Mean Square Error (RMSE). The former is generated from distance measurement. The sampling rate of the recorded sound is 44.1kHz. Fast Fourier Transform (FFT) is applied on 0.1 seconds intervals of the recorded sound with minimisation of the spectral leakage using the Hamming window. The frequency peaks are detected from the spectrogram matrices to get the most appropriate FPM between the reference and sample data. The position detection of the monitored person is based on the distance between that captured from the learning and listening phases of the system in real-time. A typical furnished one-bedroom flat (flat No.2) is used to validate the system. The topologies and floorings of flats No.1 and No.2 are different. The validation is applied based on "happy" and "unusual" but typical behaviours. Happy ones include typical TADLs of a healthy elderly person living alone with a risk metric higher than 8. Unusual one's mimic acute or chronic activities (or lack thereof), for example, falling and remaining on the floor, or staying in bed for long periods, i.e., scenarios when an elderly person may be in a compromised situation which is detected by a sudden drop of the risk metric (lower than 4) in real-time. Machine learning classification algorithms are used to identify the location, activity, and time interval in real-time, with a promising early performance of 94% in detecting the right activity and the right room at the right time.
    • Digital Education Resource Mining for Decision Support

      Not named; AL Fanah, Muna M.S. (University of BradfordFaculty of Engineering and Informatics. Department of Computer Science, 2021)
      Nowadays education becomes a competitive and challenging domain, both na­tionally and internationally in terms of quality, visibility, experience of aca­demic delivery affecting institutions, applicants, regulatory bodies. Currently data becomes more available for the general and public use, and plays also an increasingly significant role in decision support for education topics. For example, world university rankings (WUR) such as Quacquarelli Symonds (QS), Central World University Rankings (CWUR), Times Higher Education (Times) and national university rankings (e.g. the Guardian newspaper Best UK Universities and the Complete University Guide league tables) have published their data for many years now and are increasingly used in such decision making processes by institutions and general public.
    • Towards The Total Synthesis Of Withanolide E And Physachenolide C

      Afarinkia, Kamyar; Vinader, Victoria; Pors, Klaus; Anees, Muhammad (University of BradfordInstitute of Cancer Therapeutics. School of Pharmacy and Medical Sciences. Faculty of Life Sciences, 2020)
      Withanolides are a class of ergostane natural products found in plants of family Solanaceae. Plants of this family are used in traditional medicine in Asia and South America. Recently, a series of 17β-hydroxy withanolides were identified from high-throughput screens as inhibitors of androgen-induced changes in gene expression of prostate cancer cells. Therefore, these compounds may have important applications as new therapies against prostate cancer. We have devised a synthetic route to members of this family and their analogues which allows stereoselective introduction of C14, C17 and C20 hydroxyl groups in separate steps. This will allow preparation of differentially hydroxylated analogues so as to identify which contributes to the potency and thus gain a better understanding of the SAR of this class of bioactive molecules. As part of this we have shown that the stereochemical outcome of the epoxidation of Δ 14-15 cholestanes with m-CPBA is controlled by the steric bulk of a C17 substituent. When the C17 is in the β configuration, the epoxide is formed on the α face, whereas if the C17 is trigonal (flat) or the substituent is in the α configuration, the epoxide is formed on the β face. The presence of a hydroxyl substituent at C20 does not influence the stereochemical outcome of the epoxidation. We have successfully introduced aldehyde functionality to the lateral side chain 14 hydroxyl compound. This aldehyde compound is a key intermediate from which many of the withanolides can be made. We have also investigated the introduction of a hydroxyl at the C18 as an entry into the physachenolides. Finally, we have carried out an assessment of the potency of the synthesised compounds against hormone-insensitive prostate cancer cell line, PC-3.
    • Shia Political Islam in Iran. A political and economic approach

      Shahi, Afshin; Batonyi, Gabor; Mehrabinejad, Hossein (University of BradfordFaculty of Management. Law & Social Sciences, 2019)
      Although Islamism could be traced back to the seventh century when prophet Mohamad died and conflict between Shia and Sunni started, the recent growth of Islamism and emerging of new phenomena such as establishing Muslim Brotherhood in Egypt in 1920s, Iranian Islamic revolution in 1979, and some other Islamists groups like Hezbollah, and Al-Qaida highlighted the importance of Islamism. Moreover, forming the new Islamists in Syria, Iraq, and Yemen after the Arab uprising in 2010 which intensified the conflict between Shia and Sunni increased the concerns over increase in sectarianism in the Middle East. Considering the significance of Shia groups in recent movements, it is important to have a deep and comprehensive understanding of the nature and function of Shia Political Islam. Despite internal and external concerns, Shia Political Islam has emerged and continued to have control over power in Iran for more than four decades. The post-revolutionary Islamic government has been able to keep its power through reviving the Shia Movement since the 1979 Islamic revolution. Therefore, this thesis asks ‘how has Shia political Islam managed to survive in Iran over the past four decades? The answer to this question relies specifically on understanding the nature of Shia ideology and how the Shia control entities’ access to petrodollars. The study aims to clarify the concept of Shiism and explain the mechanism of the survival and continuation of the Shia movement in Iran through the lens of Social Movement Theory. This thesis argues that the essential mobilisers of the Shia Movement like the IRGC, the Basij and mosques have succeeded in sustaining the survival of the Shia Political Islam. The durability of this political approach lies in actively reviving the origins of the Shia movement, utilising Shia values, religious symbols and holy events such as Ashura, and financially rewarding the Movement with petrodollars. The mobilisers, especially the IRGC, use these values as a steering fuel to run the Shia Movement and suppress any security threat to its survival. For instance, after the 2009 presidential elections, the Green Movement was a serious security threat to the Islamic Republic and the political approach Shia political Islam. However, the IRGC and the Basij employed Shia symbols to mobilise their social base in a counter-movement in 2019 to overcome the threat of the Green Movement. The thesis concludes that if the Shia mobiliser organisations keep supporting the Shia Movement by utilising Shia values, religious symbols, and available economic resources such as petrodollars, Shia political Islam will stay resilient and survive.
    • Adaptive and Robust Multi-Gigabit Techniques Based MmWave Massive MU-MIMO Beamforming For 5G Wireless and Mobile Communications Systems. A Road Map for Simple and Robust Beamforming Scheme and Algorithms Based Wideband MmWave Massive MU-MIMO for 5G Wireless and Mobile Communications Systems

      Abd-Alhameed, Raed A.; Alabdullah, Ali AbdulMohsin S. (University of BradfordFaculty of Engineering and Informatics, 2021)
      Over recent years, the research and studies have focused on innovative solutions in various aspects and phases related to the high demands on data rate and energy for fifth-generation and beyond (B5G). This thesis aims to improve the energy efficiency, error rates, low-resolution ADCs/DACs, antenna array structures and sum-rate performances of a single cell downlink broadband millimetre-wave (mmWave) systems with orthogonal frequency division multiplexing (OFDM) modulation and deploying multi-user massive multiple inputs multiple outputs (MU mMIMO) by applying robust beamforming techniques and detection algorithms that support multiple streams per user (UE) in various environments and scenarios to achieve low complexity system design with reliable performance and significant improvement in users perceived quality of service (QoS). The performance of the four 5G candidate mmWave frequencies, 28 GHz, 39 GHz, 60 GHz, and 73 GHz, are investigated for indoor/outdoor propagation scenarios, including path loss models and multipath delay spread values. Results are compared to confirm that the received power and delay spread is decreased with increasing frequency. The results were also validated with the measurement findings for 60 GHz. Then several proposed design models of beamforming are studied and implemented modified algorithms of Hybrid Beamforming (HBF) approaches in indoor/outdoor scenarios over large scale fading wideband mmWave /Raleigh channels. Firstly, three beamforming based diagonalize the Equivalent Virtual Channel Matrix (EVCM) schemes with the optimal linear combining methods are presented to overcoming the self-interference problems in Quasi-Orthogonal-Space Time Block Code (QO-STBC) systems over narrowband mmWave Single-User mMIMO (SU mMIMO). The evaluated results show that the proposed beamforming based- Single Value Decomposition (SVD) outperforms the conventional beamforming and standard QO-STBC techniques in terms of BER and spectrum efficiency. Next, the proposed HBF algorithm approaches with the fully/ partially connected structures are developed and applied for sum-rate and symbol error rate (SER) performance maximization MU mMIMO-OFDM system, including HBF based on block diagonalization (BD) method Constraint/Unconstraint RF Power, Codebook, Kalman schemes. In addition, the modified near optimal linear HBF-Zero Forcing (HBF-ZF) and HBF-Minimum Mean Square Error (HBF MMSE) schemes, considering both fully-connected and partially-connected structures. Finally, Simulation results using MATLAB platform, demonstrate that the proposed HBF based codebook and most likely HBF based-unconstraint RF power algorithms achieve significant performance gains in terms SER and sum-rate efficiency as well as show high immunity against the deformities and disturbances in the system compared with other HBF algorithm schemes.
    • Optimizing Remote Sensing Methodology for Burial Mounds in the United States and United Kingdom

      Gaffney, Christopher F.; Batt, Catherine M.; Corkum II, Alexander C. (University of BradfordFaculty of Life Sciences. School of Archaeological and Forensic Sciences, 2019)
      Within the archaeological record ‘mounds’ are often ubiquitous. They are common in many ancient cultures, and they vary in size, construction techniques and use. This research is focused upon optimizing the use of remote sensing for the non-invasive study of mounds both in the United States and the United Kingdom. This thesis presents three representative earthen mound sites and proposes a comprehensive and modular survey methodology to guide the planning and execution of a mound survey tailored to the unique requirements presented by the cultural resource at a particular location. In doing so, the research has provided optimized approaches to high resolution three-dimensional topographic models using a variety of digital methods. These models have been shown to accurately capture the variability of the modern ground surface, which is of vital importance to the management of the mounds. Furthermore, these models have proved vital for integrating geophysical methods into the holistic workspace, thereby providing a better archaeological understanding of the below ground remains. Every mound surveyed presented different challenges, and therefore had to be approached in a slightly different way. However, the general methodology was highly effective for both characterizing below-ground archaeological and natural anomalies, and for assessing the state of preservation of all mounds surveyed. As a result, a flowchart has been generated for non-invasive assessment of mounds in general. If followed, this will allow the production of a “snapshot” of the mound or mound group at a fixed point in time with the resolution necessary to produce useful and insightful interpretation. While this research focuses on the application of geophysical and topographic survey in the United Kingdom and United States to a mound or mound group, this methodology and the associated outcomes can be valuable more globally not only for archaeology, but also heritage management.
    • Interactions between human industry and woodland ecology in the South Pennines

      Thompson, Gill B.; Gaffney, Christopher F.; Lewis, Hywel (University of BradfordFaculty of Life Sciences. School of Archaeological and Forensic Sciences, 2019)
      This research project used many disciplines to examine the impacts of industrialisation on the wooded landscape of the South Pennines. The woodlands of this upland region are characterised by their small size and steep topography. Nevertheless, they exhibit a rich archaeology of management from the medieval period onwards. Field survey of case study sites was combined with charcoal analysis from excavated burning platforms, palynology of soil cores, tree ring analysis and ecological survey. This was set within a historical context, particularly focusing on the regional industries of iron, leather and textiles, in order to understand the economic motivations for changes in woodland management. The woodlands examined showed a diverse range of histories. Some had a strong correlation with models of changing woodland management culture of neighbouring regions, particularly the evolution of systematic oak-dominated coppice in response to industrial demands. Woodland management in the South Pennines was more sensitive to industries which created dispersed demand from many actors than to bulk demand from centralised industries and responded to the changing economics of the fossil fuel era. The dominance of freehold tenure also contributed to many woodlands being managed in an unsystematic manner and the survival of private wood pasture alongside timber harvesting.
    • Analysis and pattern mapping of organic interfaces by means of seismic geophysical technologies to investigate archaeological palaeolandscapes beneath the Southern North Sea

      Gaffney, Vincent L.; Fitch, Simon; Fraser, Andrew I. (University of BradfordDepartment of Archaeological & Forensic Sciences. School of Life Sciences, 2021)
      Investigating the archaeology of submerged landscapes beneath many metres of sea and buried under modern sands requires an understanding of the terrestrial surface as it may have been prior to the inundation. To do this, environmental evidence is required from contextualised in-situ locations and the best material evidence for preservation of archaeology, organic remains, dating proxies, pollen, diatoms, microfossils, coleoptera etc. is peat. This research supports the search for peat in submarine environments by interpreting seismic surveys of the sub-sea floor and analysing reflective signals for distinctive organic responses. By means of sedimental analysis and ground observation, the research sets out to differentiate between organic signals, to allow for the identification and location of shallow peat beds within features of a palaeolandscape. Using these results should provide an opportunity to target such peat beds in an archaeologically focused coring programme. The research also examines ways in which organic responses may be mapped over larger areas in order to integrate the results into a wider scale landscape model identifying potential peatland, marsh, valley fen and lowland areas. Finally, the research introduces an artificial intelligence neural networking technology for the identification of organic interfaces in seismic surveys, examining three different ways in which this could be accomplished using specialist computer tools and software.
    • Evaluation of the Effect of Critical Process and Formulation Parameters on the Attributes of Nanoparticles Produced by Microfluidics. Design of Experiments Approach for Optimisation of Process and Formulation Parameters Affecting the Fabrication of Nanocrystals of Poorly Water-Soluble Drug Using Anti-solvent Precipitation in Microfluidic

      Assi, Khaled H.; Isreb, Mohammad; Obeed, Muthana M. (University of BradfordSchool of Pharmacy and Medical Sciences, 2021)
      Advanced drug delivery systems have shown immense success through nanotechnology which overcomes the challenges posed by large sized particles such as poor solubility, bioavailability, absorption, and target-specific delivery. This study focuses on nano sizing by application of microreactor technology and nanoparticles to obtain polymeric particulate with a selection of model drugs for inhalation drug delivery routes. The development of nanoparticles of two challenging compounds in terms of solubility and permeability, namely Ibuprofen (IBU) and Salmeterol (SAL), was conducted using a continuous, controlled, and scalable system offered by microfluidic reactor with the incorporation of anti-solvent approach. The research explores the potential of this technology to enhance absorption rate and hence bioavailability of IBU via oral route, and SAL via inhalation. IBU, an anti-inflammatory drug, is classified as BCS Class II drug with low solubility and high permeability. SAL is a selective long acting β2-agonist which is co-dispensed along with a short-acting β2-agonist for quick relief of acute bronchoconstriction due to its long onset of action. This lack of the ‘kick’ effect in SAL can be attributed to its relatively higher lipophilicity which causes a delay in the diffusion to the β2 receptors on the smooth muscles. It is therefore feasible to assume that increasing the dissolution and/or diffusion rate of SAL in the interstitial fluids would reduce the delay between administration and the onset of action of this drug which would be beneficial to patients. Process and formulation parameters were investigated to optimize the production and stability of nano particles of both drugs using Y shaped microfluidic reactors. IBU results show that the smaller the angle between the two inlets were the smaller the particle size achieved. Moreover, the particle size increased with increasing the concentration of IBU solution. The effect of the polymer mixture ratio (PVP/HPMC) on the initial particle size was not clear though. The smallest particle size (113 nm) was achieved using 10° Y shaped chip with IBU concentration of 1 mg/mL and a polymer mixture of 0.3% w/v PVP and 0.5% w/v HPMC. Using a polymer mixture of 0.5% w/v of each polymer though yielded a better PDI (140nm and PDI of 0.5). Same observations were noted when the syringe pumps were replaced with a non-pulsatile pressure pump. Particle size though dropped significantly to 33nm. Stability data showed that all systems were practically stable regardless of the process or formulation parameters. In addition, a considerable 2.5 fold increase in dissolution rate was observed in the first 20 minutes when compared to the raw material. The optimized parameters were applied to SAL to produce nanocrystals with best result (59 nm) were obtained using 50µg/mL Salmeterol with microfluidics inlet angle 10° with non-pulse syringe pump. The stabilizing mixture was PVP 0.8% w/v and Tween 80 at a concentration of 0.02%. This approach offered a basis for the generation of nano sized SAL particles with higher fine particle fraction and better deposition in NGI than currently marketed formulations, thus providing a more efficient drug dose delivery and lung deposition.
    • Synthesis and Characterisation of Dual CCR7/CXCR4 Antagonists

      Not named; Izidro, Mario C. (University of BradfordInstitute of Cancer Therapeutics. Faculty of Life Sciences, 2019)
      Metastasis is a major cause of death in cancer patients but currently there are no drugs available for its treatment. Hence there is an urgent clinical need for identifying and developing anti-metastatic drugs. The activation of CC chemokine receptor 7 (CCR7) and C-X-C chemokine receptor type 4 (CXCR4) plays an important role in lymph node metastasis in a variety of cancers. Indeed, in patients with tumours which are positive for CCR7 and/or CXCR4 expression, prognosis and survival are poorer than those whose tumours are negative for these receptors. CCR7 and/or CXCR4 activation, in addition to being involved in inducing invasive phenotypes in cancer cells, promotes tumour cell growth and survival. Our group has previously identified a series of sulfonamides as CCR7 antagonists. This project aims to extend on those studies and to develop a dual CCR7 and CXCR4 antagonist to reduce metastasis in cancer. Novel potent biaryl sulfonamide CCR7 antagonists were synthesised and assessed by calcium flux assay. Several potential dual CCR7 and CXCR4 biaryl sulfonamide antagonists have been synthesised, these are hybrid compounds incorporating features from CCR7 antagonists of this project, and from known sulfonamide CXCR4 antagonists. The most potent of such compound was able to inhibit CCR7 activation in calcium flux assay (95% inhibition at 1 µM), however, the relative potency of these compounds as CXCR4 antagonists was low. Molecular docking was used to investigate the binding mode of the synthesised compounds in CCR7 and CXCR4. The generated docking poses were able to rationalise some of the calcium flux assay results.
    • Targeting the formyl peptide receptor 1 for treatment of glioblastoma

      Afarinkia, Kamyar; Shnyder, Steven D.; Ahmet, Djevdet S. (University of BradfordFaculty of Life Sciences, 2021)
      Background and Aims Gliomas account for over half of all primary brain tumours and have a very poor prognosis, with a median survival of less than two years. There is an urgent and unmet clinical need to develop new therapies against glioma. Recent reports have indicated the overexpression of FPR1 in gliomas particularly in high grade gliomas. The aim of this project was to identify and synthesise small molecule FPR1 antagonists, and to demonstrate a proof of principle in preclinical in vitro and in vivo models that small molecule FPR1 antagonism can retard expansion of glioma. Methods A number of small molecule FPR1 antagonists were identified by in silico design, or from the literature and then were prepared using chemical synthesis. FPR1 antagonists were evaluated in vitro for their ability to abrogate FPR1-induced cellular responses in a range of models including calcium mobilisation, cell migration, and invasion. The efficacy of FPR1 antagonist ICT12035 in vivo was assessed in a U-87 MG subcutaneous xenograft model. Results Virtual high throughput screening using a homology model of FPR1 led to the identification of two small molecule FPR1 antagonists. At the same time chemical synthesis of two other antagonists, ICT5100 and ICT12035 as well as their analogues were carried out. The FPR1 antagonists were assessed in calcium flux assay which gave an insight into their structure-activity relationship. Further investigation of both ICT5100 and ICT12035 demonstrated that both small molecule FPR1 antagonists were effective at abrogating FPR1-induced calcium mobilisation, migration, and invasion in U- 87 MG in vitro models in a dose-dependent manner. ICT12035 is a particularly selective and potent inhibitor of FPR1 with an IC50 of 37.7 nM in calcium flux assay. Additionally, it was shown that the FPR1 antagonist ICT12035 was able to arrest the growth rate of U-87 MG xenografted tumours in mice. Conclusion The results demonstrate that targeting FPR1 by a small molecule antagonist such as ICT12035, could provide a potential new therapy for the treatment of glioblastoma.
    • The significance of ECOWAS Norms and Mechanisms in Conflict Prevention and Security-Building in West Africa since 2000

      Greene, owen J.; Pankhurst, Donna T.; Onyekwere, Ignatius E. (University of BradfordPeace Studies and International Development. Faculty of Management Law and Social Sciences, 2020)
      This thesis examines the roles and significance of ECOWAS (Economic Community of West Africa States) in conflict prevention, crisis response and security-building processes in West Africa, particularly since 2000. The importance of developing regional institutions and capacities for peace and security-building in Sub-Saharan Africa has been widely recognised since at least the mid-1990s. Not only has the African Union developed important peace and security building aims and roles, but so too have several of the sub-regional organisations in Africa, including ECOWAS in West Africa. In the late 1990s, ECOWAS Member States achieved a number of noteworthy sub-regional agreements on ECOWAS norms and mechanisms for conflict prevention, crisis response, and peace and security –building in West Africa. These agreements and mechanisms have subsequently been further developed since 2000, in a dynamic process that was informed by experience with efforts to respond to a range of crises and conflicts in the region. This thesis critically examines this process, focussing particularly on the extent to which, and how, ECOWAS norms, institutions and mechanism have continued not only to develop but also to be influential in practice. Our research demonstrates that the ECOWAS agreements and norms established by 2000 have continued subsequently to be dynamically developed and used by ECOWAS member states and West African networks, in close interaction with several international partners. It argues that these norms and mechanisms have played significant roles in influencing actual policies, practices and missions. They have therefore proved to be more than shallow symbolic or paper agreements, despite the political fragility and divisions of the region and most of its states. We argue that this cannot be adequately understood using single explanatory frameworks, such as Nigeria’s hegemonic influence or instrumental influence of external Actors such as UN, EU or USA, as has often been suggested. Adequate explanations need to combine these factors with others, including relatively consistent investment in regional norms and institutions by coalitions of some West African states (including Ghana, Senegal and Nigeria) together with civil society and parliamentary networks. Our research then examines in detail the extent to which, and how, ECOWAS norms and mechanisms on conflict prevention, crisis response and security sector reform were significant and influential in ECOWAS’ responses to the crises and conflicts in Cote D’Ivoire, Mali and to a lesser extent in Gambia since 2003; and also how these crises were in turn influential in the further development of ECOWAS norms in these areas. We demonstrate numerous weaknesses in the implementation and effectiveness in these norms; and limitations in their diffusion and influence. However, we argue that such weaknesses and limitations are typical of regional peace and security norms everywhere, including much more stable and developed regions. Equally significant is that substantial coalitions exist between ECOWAS member states and stakeholders. Despite obvious tensions, ECOWAS, AU, UN and other countries such as France continue to work to address inherent tensions and develop mutually beneficial collaborations that enhance effective conflict prevention in the sub-region. The study draws on the knowledge created within this this thesis to propose a framework for conflict intervention.
    • What is the Role of a Pharmacist in a Parkinson’s Disease Interdisciplinary Team?

      Morgan, Julie D.; Breen, Liz; Powell, Catherine; Dhap, Jaswinder L. (University of BradfordFaculty of Life Sciences, 2021)
      The care of people with Parkinson’s disease (PD) involves input from different healthcare professionals (HCPs). A literature search identified that the HCPs involved in PD multidisciplinary (MDT) clinics, including interdisciplinary team (IDT), varied both in the number and type of HCPs. None of the studies identified involved pharmacists. Pharmacists have shown benefits when working in MDTs for other long-term conditions (LTCs); however, their role in PD MDTs was identified as a gap in the literature. The aim of the study was to determine the role of pharmacists in a PD IDT. Patients attended a PD IDT clinic comprising PD nurse, physiotherapist, occupational therapist and pharmacist. A mixed methods convergent design was used to collect both qualitative and quantitative data. Qualitative focus group and interview data were analysed using The Framework Method. Quantitative data analysis involved counts of HCP interventions. Pharmacists can support PD IDTs as they have in other LTC MDTs by conducting holistic medication reviews. Three new roles were identified for pharmacists in PD IDTs as: 1) independent prescribing, 2) supporting HCPS in their roles by supporting staff knowledge, and 3) leading the PD IDT clinics. Quantitative data showed the pharmacist made a medication review intervention for all patients. HCPs and patients identified the roles and value of involving pharmacists in PD IDTs. The PD IDT clinics offer a holistic approach to patient care and a greater opportunity for patients to be involved. The findings identified a ‘review-shared care template’ for PD IDTs and recommends development of a ‘pharmacist’s PD competency framework’.
    • The Significance of the Depositional Microenvironment in the Decomposition of Dismembered Body Parts

      Wilson, Andrew S.; Fletcher, Jon; Janaway, Robert C.; Franicevic, Branka (University of BradfordSchool of Archaeology and Forensic. Faculty of Life Sciences, 2018)
      A scarcity of experimental studies covering the decomposition of dismembered body parts has created a gap in knowledge of the effect of dismemberment on the estimation of post-mortem interval (PMI) and their post-mortem history in a forensic context. The aim of this study was to record the decay of detached body parts in some depositional settings where they are likely to be disposed of: burial, wrapping and freezing. A series of controlled laboratory experiments was carried out using Sus scrofa body parts and pork belly, to understand how ambient temperature, soil moisture, and wrapping and freezing of body parts affected their decomposition. Rates of decay were subject to a higher temperature and soil moisture level in a burial microenvironment, with metabolic microbial activity confirming the results. Temperature was a predominant factor in the decay rates of wrapped body parts, with a raised ambient temperature causing even higher temperature in the wrapped microenvironment, resulting in accelerated decay rates. Freezing decelerated the decomposition of body parts, retarding microbial growth and activity and causing differential decomposition between body parts. Freezing demonstrated morphological changes in body parts specific to this microenvironment. Predominantly Gram-negative bacteria that may be associated with body microflora were involved in decomposition in all three microenvironments. Taphonomic, chemical and microbiological analyses carried out in this study have a potential for forensic application in the examination of dismembered remains that have been deposited in freezing and indoor settings. Further experiments are necessary to understand buried decomposition patterns in field conditions.