Bradford Scholars is the University of Bradford online research archive. Access is free to anyone interested in research being conducted at Bradford. In the repository you will find a range of materials from journal articles and conference papers to research reports and theses.
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Does Cyberspace outdate Jurisdictional Defamation Laws?Cyberspace produces friction when the law is implemented by domestic courts using 'state-laws'. These laws are based on a ‘physical presence’ of an individual within the territory. It elevates conflicts relating to cyberspace jurisdiction. This research examines private international law complications associated with cyberspace. The paradigm of libel that takes place within the domain of social media is used to evaluate the utility of traditional laws. This research is conducted using ‘black-letter’ methodology, keeping in mind the changes constituted by the Defamation Act 2013. It pinpoints that the instantaneous nature of social media communication demands an unambiguous exercise of 'personal-jurisdiction', beyond the doctrine of territoriality. An innovation to the code of Civil Procedure is recommended to revise the process of service for non-EU defendants. The permission to serve a writ via social networks (or to the relevant Embassy of the defendant’s domicile state), can accelerate the traditional judicial process. This thesis can be utilised as a roadmap by libel victims for preliminary information. It contributes to the knowledge by discovering that the thresholds under Section 1 and Section 9 of the Defamation Act 2013 overlap with the conventional ‘forum-conveniens’ tests. This crossover is causing legal uncertainty in the application of existing rules to the digital libel proceedings. Section 1 and Section 9 thresholds do not fulfil the purpose of eliminating ‘libel-tourism’ and maintaining a balance between speech freedom and reputation rights. They raised the bar for potential victims and restricted their rights to justice. It is proposed that the traditional ‘conveniens test’ must be used for social media libel victims to produce legal certainty in cyberspace defamation.
Exploring the Impact of Business Intelligence (BI) Use on Organisational Power Dynamics: A National Health Service (NHS) Case StudyThe public sector, particularly healthcare organisations are under ever increasing pressure to do more with less. This coupled with the need to keep up to the constant technological changes and ever increasing abundance of information has led to many public sector organisations adopting Business Intelligence (BI) in order to leverage business value and improve decision-making. However, many organisations such as the National Health Service (NHS) continue to fail in their Information Technology (IT) related initiatives. While the rise of BI and its growing influence in organisations has attracted much academic attention, this has largely been from architectural, design and technological perspectives, whilst little is known about how BI is used by various organisational actors to reach decisions, nor much is understood regarding its resulting impact on organisational power dynamics. Thus, there remains an under researched area of discussion in the literature from the perspective of BI users. While studies report how BI can impact organisational effectiveness, facilitate data driven decision making and supposedly overcome intuitive decision making, the extent to which BI impacts and alters power dynamics between organisational actors across the organisation has received little attention. Accordingly, this research adopts a qualitative case study approach to explore power resulting from BI use within a large NHS trust by conducting 30 semi-structured interviews consisting of operational managers and BI analysts. Through taking a human-centric approach, this research uncovers how BI is altering power dynamics between organisational actors, whereby BI analysts are becoming increasingly influential as a result of their analytical skills. It was found that operational managers are becoming more reliant upon data analysts, resulting in the analysts having more and more influence. However, this research finds it is only when the analysts supplement their technical skill-set with their institutional knowledge, that they have the ability to influence and enact power within the organisational settings. The research also offers insights into the contestations and conflicts which arise from the use of BI, between operational managers and analysts as well as between in-house analysts, based in the operation setting and the centralised analysts, operating across the entire trust. Accordingly, this research empirically validates a BI Power Enactment Framework and proposes the BI Power Matrix, which may assist policy makers in identifying determining key factors which are contributory to the success or failure of technological initiatives.
Evaluation of the critical parameters and polymeric coat performance in compressed multiparticulate systemsCompression of coated pellets is a practical alternative to capsule filling. The current practice is to add cushioning agents to minimize the stress on the coated pellets. Cushioning agents however add bulkiness and reduce the overall drug loading capacity. In this study, we investigated the performance of compressed coated pellets with no cushioning agent to evaluate the feasibility of predicting the coat behaviour using thermo-mechanical and rheological analysis techniques. Different coating formulations were made of ethyl cellulose (EC) as a coating polymer and two different kinds of additives were incorporated into the polymeric coating solution. Triethyl Citrate (TEC) and Polyethylene glycol 400(PEG400) were used as plasticizers at different levels to the coating formulations (10%, 20%, 30%). Thermal, mechanical and rheological measurements of the coating film formulations were achieved to investigate the effect of plasticizers. Thermal gravimetric analysis results (TGA) showed higher residual moisture content in films plasticised with PEG 400 compared to their TEC counterparts. Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA) and Parallel Plate Shear Rheometer (PPSR) were used to study the influence of the level and type of plasticisers incorporated in coating film formulation on the performance of the coating film. In this study, both DSC and DMA were used to investigate the Tg for each film coating formulation in order to evaluate the effect of the additives. In general DMA results for the Tg value of the films were always higher by 10-20% than those measured by the DSC. Furthermore, clamp size and the frequency of the oscillation have an influence on the evaluation of Tg. Complex viscosity for different coating film formulations revealed that the shear hinning gradient changes with temperature and plasticiser type and concentration. The value of complex viscosity from DMA and PPSR exhibits power law behaviour. The rheological moduli were indirectly affected by the level of plasticiser. There was a discrepancy between the complex viscosity results obtained from both DMA and PPSR at similar temperature but they follow the same trend. The non plasticized polymer showed a 10 time higher complex viscosity values when measured by DMA over that measured by PPSR. The difference was smaller in plasticized films but it was not consistent. Therefore a consistent coefficient to correlate the DMA and PPSR couldn’t be accurately determined Coated pellets were compressed and key process parameters were evaluated. The obtained results revealed that the coating thickness has a significant effect on the release profile of the final products. It was found that by increasing the coating film thickness, the percentage released decreased. Also the compression force has lower influence on the drug release profile, while the dwell time has very low effect on the percentage release from the final products. Optimum release profile was obtained at a coating level of 5.5% w/w and a compression force of 4700N In conclusion, the elasticity of the plasticised EC films in this study meant that the internal stress is not dissipated during compression and the dwell time range that was used in this experiment. Increasing the thickness therefore was necessary to enhance the strength of the film and avoid cracking. The mechanical and rheological profiling was helpful therefore to understand the behaviour of the coated pellets and predict the film properties at various steps of the process of coating and compression (i.e., various shear rate regimes). Experimental design approach to studying the key process and formulation parameters helped identify the optimum values for the process.
Impact of material attributes & process parameters on critical quality attributes of the amorphous solid dispersion products obtained using hot melt extrusionThe feasibility of hot melt extrusion (HME) was explored for development of amorphous solid dispersion systems. Controlled release formulations were developed using a cellulose based derivative, AffinisolTMHPMC 100cP and 4M grades. BCS class II drugs ibuprofen and posaconazole were selected due to their difference in glass transition temperature and lipophilicity. This study focused on investigation of the impact the material attributes and process parameters on the critical quality attributes in preparation of amorphous solid dispersions using hot melt extrusion. The critical quality attributes were sub divided into three main attributes of material, process and product. Rheology of ibuprofen-Affinisol 100cP from melt phase to extrudate phase was tracked. A partial factorial design was carried out to investigate the critical parameters affecting HME. For optimisation of 40%IBU-Affinisol 100cP blends, a feed rate of 0.6kg/hr, screw speed of 500rpm and screw configuration with two mixing elements were found to be optimum for single phase extrudates. ATR-FTIR spectroscopy was found to be an indirect technique of choice in predicting the maximum ibuprofen drug load within extrudates. Prediction was based on the prepared extrudates without charging them to stability conditions. An alternative strategy of incorporation of di-carboxylic acids to increase the dissolution of posaconazole-Affinisol 4M blends was investigated. Succinic acid and L- malic acid incorporation was found to increase the dissolution of posaconazole. Although, the extrudates crystallised out quicker than the naïve posaconazole-Affinisol 4M, but free posaconazole formed eutectic and co-crystal with succinic and L-malic acid within extrudates. This lead to an increase in dissolution of the extrudates compared to day 0.
Evaluation of telomerase activity and telomerase inhibitors in Head and Neck cancerCancer is a major cause of morbidity and mortality with increasing incidence worldwide. Early detection of cancers and better treatments would improve the outcome for patients. The overall 5-year survival rates of head and neck squamous cell carcinoma have not improved in the past several decades due to diagnosis at advanced stages and recurrent disease. Early detection and improved chemotherapy drugs are two key areas that are required to help to improve the prognosis for this disease. This thesis focuses on the enzyme telomerase which is known to contribute to one of the hallmarks of cancer (immortality). Elevated telomerase activity has been observed in the majority of cancer cells but not in most normal human cells so there is an opportunity to use telomerase as a biomarker for disease. This first part of this study assessed telomerase activity in saliva and tissues of head and neck squamous cell cancer patients. The Telomerase PCR-ELISA kit was used to assess telomerase activity in the saliva of patients with confirmed oral carcinomas and its expression was analysed in paraffin embedded tissue using immunohistochemistry (IHC). Whilst telomerase was detected in cell lines, no telomerase activity was detected in saliva samples from patients but was detectable in IHC specimens. The second part of the study focused on the pharmacological evaluation of a series of small molecule G–quadruplex DNA binding agents as potential telomerase inhibitors. A total of 19 telomerase inhibitors were identified but of these, only 4 were specific inhibitors of telomerase. These compounds also caused toxicity to cell lines following a 2 hour drug exposure at doses that also inhibit telomerase activity. Further studies are required to explore these compounds further. In conclusion, the results of this study have demonstrated that detection of telomerase activity I the saliva of patients with oral cancers is unlikely to be useful in terms of detecting oral cancers before symptoms of the disease are clinically manifest. A series of novel and specific inhibitors of telomerase have been identified and further studies are required to develop these compounds further.