Poly (D,L-Lactide) based microspheres for pulmonary delivery of proteins

Initial work focused on the preparation, optimisation and characterisation of poly (D,L-lactide) (PLA) microspheres with the aim of optimising their formulation based on minimizing the particle size into the range suitable for pulmonary delivery to alveoli. In order to produce dry powders and to enhance their long-term physico-chemical stability, microspheres were prepared as a dry powder via freeze-drying. Optimisation studies showed that using appropriate concentrations of polymer 3% (w/v) in organic phase and emulsifier 10% (w/v) in external aqueous phase, the double solvent evaporation method produced high protein loading microspheres (72 ± 0.5%) with an appropriate particle size for pulmonary drug delivery. Combined use of trehalose and leucine as cyroprotectants (6% and 1% respectively, w/v) produced freeze-dried powders with the best aerosolisation profile among those tested. Although the freeze-dried PLA microsphere powders were not particularly respirable in dry powder inhalation, nebulisation of the rehydrated powders using an ultrasonic nebuliser resulted in improved aerosilisation performance compared to the air-jet nebuliser. When tested in vitro using a macrophage cell line, the PLA microspheres system exhibited a low cytotoxicity and the microspheres induced phagocytic activity in macrophages. However, interestingly, the addition of an immunomodulator to the microsphere formulations (4%, w/w of polymer) reduced this phagocytic activity and macrophage activation compared to microspheres formulated using PLA alone. This suggested that the addition of trehalose dibehenate may not enhance the ability of these microspheres to be used as vaccine delivery systems.

Strategic planning as communicative process

This thesis looks at the construction of a strategic plan within a British university (Unico). After a change in leadership, the well-known strategic planning sequence was adopted to set directions according to Unico’s three Missions, followed by the development of respective goals and measures. The evolving strategic content coincided with the development of Unico’s strategic plan. I was able to follow Unico’s planning efforts over 10 months, from first planning meeting to completion of its strategic plan. The main data source provided non-participant observation (n = 25) and ten versions of Unico’s strategic plan. Additionally, seventy-six interviews were held with participants at various points. In order to examine the strategic plan’s construction, I reconceptualised strategic planning as a communicative process consisting of oral talk and written text. Through this interplay strategic planning activities come in to being. Such reconceptualisation provided a conceptual framework to study the in situ interactions without neglecting contextual characteristics embedding the communicative process. Strategic plans are currently seen as promoting inflexibility and reinforcing the institutional nature of formal strategic planning. Adopting dialogism, as advocated by Bakhtin and Ricoeur, this research provides novel insights into the dialogic of strategy talk and strategy text, such as a strategic plan. Findings illustrated that a strategic plan production cycle provided a meaning making platform for its participants. Through recurrently amending the plan, its content became increasingly specific while at the same time reflecting agreed terminology. This thesis offers an alternative view on strategic planning, elaborates on the strategy-as-practice perspective, focusing on the under-explored area of individuals’ interactions at the micro level, and elaborates on the dialogic of text and agency/conversation, distinguishing between talk and text.

A deficit in encoding the order of visual sequences in developmental dyslexia: a non -phonological deficit

The present thesis tested the hypothesis of Stanovich, Siegel, & Gottardo (1997) that surface dyslexia is the result of a milder phonological deficit than that seen in phonological dyslexia coupled with reduced reading experience. We found that a group of adults with surface dyslexia showed a phonological deficit that was commensurate with that shown by a group of adults with phonological dyslexia (matched for chronological age and verbal and non-verbal IQ) and normal reading experience. We also showed that surface dyslexia cannot be accounted for by a semantic impairment or a deficit in the verbal learning and recall of lexical-semantic information (such as meaningful words), as both dyslexic subgroups performed the same. This study has replicated the results of our published study that surface dyslexia is not the consequence of a mild retardation or reduced learning opportunities but a separate impairment linked to a deficit in written lexical learning, an ability needed to create novel lexical representations from a series of unrelated visual units, which is independent from the phonological deficit (Romani, Di Betta, Tsouknida & Olson, 2008). This thesis also provided evidence that a selective nonword reading deficit in developmental dyslexia persists beyond poor phonology. This was shown by finding a nonword reading deficit even in the presence of normal regularity effects in the dyslexics (when compared to both reading and spelling-age matched controls). A nonword reading deficit was also found in the surface dyslexics. Crucially, this deficit was as strong as in the phonological dyslexics despite better functioning of the sublexical route for the former. These results suggest that a nonword reading deficit cannot be solely explained by a phonological impairment. We, thus, suggested that nonword reading should also involve another ability relating to the processing of novel visual orthographic strings, which we called 'orthographic coding'. We then investigated the ability to process series of independent units within multi-element visual arrays and its relationship with reading and spelling problems. We identified a deficit in encoding the order of visual sequences (involving both linguistic and nonlinguistic information) which was significantly associated with word and nonword processing. More importantly, we revealed significant contributions to orthographic skills in both dyslexic and control individuals, even after age, performance IQ and phonological skills were controlled. These results suggest that spelling and reading do not only tap phonological skills but also order encoding skills.

Point-by-point inscription of first-order fiber Bragg grating for C-band applications

The influence of the fiber geometry on the point-by-point inscription of fiber Bragg gratings using a femtosecond laser is highlighted. Fiber Bragg gratings with high spectral quality and strong first-order Bragg resonances within the C-band are achieved by optimizing the inscription process. Large birefringence (1.2x10-4) and high degree of polarizationdependent index modulation are observed in these gratings. Potential applications of these gratings in resonators are further illustrated. © 2007 Optical Society of America.

Polycaprolactone fibres as a potential delivery system for collagen to support bone regeneration

Poly(e-caprolactone) (PCL) is biocompatible, non-immunogenic and non-toxic, and slowly degrades, allowing sufficient time for tissue regeneration. PCL has the potential for application in bone and cartilage repair as it may provide the essential structure required for bone regeneration, however, an ideal scaffold system is still undeveloped. PCL fibres were prepared using the gravity spinning technique, in which collagen was either incorporated into or coated onto the 'as-spun' fibres, in order to develop novel biodegradable polymer fibres which will effectively deliver collagen and support the attachment and proliferation of human osteoblast (HOB) cells for bone regeneration. The physical and mechanical characteristics and cell fibre interactions were analysed. The PCL fibres were found to be highly flexible and inclusion of collagen did not alter the mechanical properties of PCL fibres. Overall, HOB cells were shown to effectively adhere and proliferate on all fibre platforms tested, although proliferation rates were enhanced by surface coating PCL fibres with collagen compared to PCL fibres incorporating collagen and PCL-only fibres. These findings highlight the potential of using gravity spun PCL fibres as a delivery platform for extracellular matrix proteins, such as collagen, in order to enhance cell adherence and proliferation for tissue repair.

Effects of fourth-order fiber dispersion on ultrashort parabolic optical pulses in the normal dispersion regime

We propose a new method for the generation of both triangular-shaped optical pulses and flat-top, coherent supercontinuum spectra using the effect of fourth-order dispersion on parabolic pulses in a passive, normally dispersive highly nonlinear fiber. The pulse reshaping process is described qualitatively and is compared to numerical simulations.

Internal branding to influence employees' brand promise delivery:a case study in Thailand

Purpose – The purpose of this paper is to understand the internal branding process from the perspective of service providers in Thailand. It will reveal the key internal branding mechanisms and empirically assess the relationship between internal branding and employees' brand attitudes and performance. Design/methodology/approach – A case study representing the Thai hotel industry is adopted with mixed methodologies. In-depth interviews are first carried out with 30 customer-interface employees in six major hotels in Thailand. On a census basis, a quantitative survey with 699 respondents from five major hotels in Thailand follows. Findings – Internal branding coordinating marketing with human resource management has a statistically significant impact on attitudinal and behavioural aspects of employees in their delivery of the brand promise. As employees' brand commitment do not have a statistically significant relationship with employees' brand performance, it is not regarded as a mediator in the link between internal branding and employees' brand performance. Practical implications – A number of significant managerial implications are drawn from this study, for example using both internal communication and training to influence employees' brand-supporting attitudes and behaviours. Still, it should be noted that the effect of internal branding on employee behaviours could be dependent on the extent to which it influences their brand attitudes. Originality/value – The paper provides valuable insights, from the key internal audience's perspectives, into an internal branding process. It has empirically shown the relationship between internal branding and the behavioural outcome as well as the partial meditating effects of employees' brand identification, commitment and loyalty.

Exploring the influences of internal branding on employees' brand promise delivery

Internal branding is increasingly seen as a doctrine to ensure employees’ delivery of the brand promise by shaping employees’ brand attitudes and behaviours. However, few studies, if any, have been conducted to understand the internal branding process from the viewpoint of employees who are the end receivers. Therefore, this study aims at exploring employees’ perceptions toward the internal branding process. It identifies the relevant mechanisms and describes how internal branding affected service employees. The challenges of its success are uncovered and discussed. Finally, managerial implications and future research directions are provided.

Nanotechnology for the delivery of vaccines

Liposomes offer an ideal platform for the delivery of subunit vaccines, due to their versatility and flexibility, which allows for antigen as well as immunostimulatory lipids and TLR agonists to become associated with these bilayered vesicles. Liposomes have the ability to protect vaccine antigen, as well as enhance delivery to antigen presenting cells, whilst the importance of cationic surface charge for delivery of TB subunit vaccines and formation of an ‘antigen depot’ may play a key role in boosting cell-mediated immunity and Th1 immune responses. The rational design of vaccine adjuvants requires the thorough investigation into the physicochemical characteristics that dictate the function of a liposomal adjuvant. Within this thesis, physicochemical characteristics were investigated in order to show any effects on the biodistribution profiles and the ensuing immune responses of these formulations. Initially the role of liposome charge within the formulation was investigated and subsequently their efficacy as vaccine adjuvants in combination with their biodistribution was measured to allow the role of formulation in vaccine function to be considered. These results showed that cationic surface charge, in combination with high loading of H56 vaccine antigen through electrostatic binding, was crucial in the promotion of the ‘depot-effect’ at the injection site which increases the initiation of Th1 cell-mediated immune responses that are required to offer protection against tuberculosis. To further investigate this, different methods of liposome production were also investigated where antigen incorporation within the vesicles as well as surface adsorption were adopted. Using the dehydration-rehydration (DRV) method (where liposomes are freeze-dried in the presence of antigen to promote antigen encapsulation) and the double emulsion (DE) method, a range of liposomes entrapping antigen were formulated. Variation in the liposome preparation method can lead to antigen entrapment within the delivery system which has been shown to be greater for DRV-formulated liposomes compared to their DE-counterparts. This resulted in no significant effect on the vaccine biodistribution profile, as well as not significantly altering the efficacy of cationic liposomal adjuvants. To further enhance the efficacy of these systems, the addition of TLR agonists either at the vesicle surface as well as within the delivery system has been displayed through variation in the preparation method. Anionic liposomal adjuvants have been formulated, which displayed rapid drainage from the injection site to the draining lymph nodes and displayed a reduction in measured Th1 immune responses. However, variation in the preparation method can alter the immune response profile for anionic liposomal adjuvants with a bias in immune response to Th2 responses being noted. Through the use of high shear mixing and stepwise incorporation, the efficient loading of TLR agonist within liposomes has been shown. However, interestingly the conjugation between lipid and non-electrostatically bound TLR agonist, followed by insertion into the bilayer of DDA/TDB resulted in localised agonist retention at the injection site and further stimulation of the Th1 immune response at the SOI, spleen and draining lymphatics as well as enhanced antibody titres.

Amino acids as cryoprotectants for liposomal delivery systems

Liposomes provide an efficient delivery system for solubilisation and delivery of both small and macro molecules. However, they suffer from the disadvantage of instability when stored as aqueous dispersions. Cryoprotection of the liposomal systems provides an effective approach to overcome poor stability whilst maintaining formulation characteristics, although, the formulation of a freeze-dried product requires the consideration of not only the selection of an appropriate cryoprotectant, but also needs careful consideration of the processing parameters including pre-freezing conditions, primary and secondary drying protocols along with optimisation of cryoprotectant concentration. This current work investigates the application of amino acids as potential cryoprotectants for the stabilisation of liposomes, and results indicate that amino acids show biphasic nature of stabilisation with 4 mol of cryoprotectant per mole of the lipid exhibiting optimum cryoprotection. The investigations of process parameters showed that the pre-freezing temperatures below the glass transition of the amino acids followed by drying for over 6 h resulted in stable formulations. Studies investigating the efficiency of drug retention showed that the cryoprotection offered by lysine was similar to that shown by trehalose, suggesting that amino acids act as effective stabilisers. ESEM analysis was carried out to monitor morphology of the rehydrated liposomes. © 2007 Elsevier B.V. All rights reserved.

Team effectiveness: a test of in-put process-output

This research addressed the question: "Which factors predict the effectiveness of healthcare teams?" It was addressed by assessing the psychometric properties of a new measure of team functioning with the use of data collected from 797 team members in 61 healthcare teams. This new measure is the Aston Team Performance Inventory (ATPI) developed by West, Markiewicz and Dawson (2005) and based on the IPO model. The ATPI was pilot tested in order to examine the reliability of this measure in the Jordanian cultural context. A sample of five teams comprising 3-6 members each was randomly selected from the Jordan Red Crescent health centers in Amman. Factors that predict team effectiveness were explored in a Jordanian sample (comprising 1622 members in 277 teams with 255 leaders from healthcare teams in hospitals in Amman) using self-report and Leader Ratings measures adapted from work by West, Borrill et al (2000) to determine team effectiveness and innovation from the leaders' point of view. The results demonstrate the validity and reliability of the measures for use in healthcare settings. Team effort and skills and leader managing had the strongest association with team processes in terms of team objectives, reflexivity, participation, task focus, creativity and innovation. Team inputs in terms of task design, team effort and skills, and organizational support were associated with team effectiveness and innovation whereas team resources were associated only with team innovation. Team objectives had the strongest mediated and direct association with team effectiveness whereas task focus had the strongest mediated and direct association with team innovation. Finally, among leadership variables, leader managing had the strongest association with team effectiveness and innovation. The theoretical and practical implications of this thesis are that: team effectiveness and innovation are influenced by multiple factors that must all be taken into account. The key factors managers need to ensure are in place for effective teams are team effort and skills, organizational support and team objectives. To conclude, the application of these findings to healthcare teams in Jordan will help improve their team effectiveness, and thus the healthcare services that they provide.

Buried clay pot irrigation for efficient and controlled water delivery

This study presents water flow (WF) into soil from several pitchers buried in the soil up to their neck and filled with water,under natural atmospheric conditions for a period of two years. Variation in daily WF into soil indicated a direct correlation with moisture deficit (MD) in atmosphere. WF increases linearly with MD for non rainy days. WF without hydraulic head through all pots varied in the order air>soil>water. Base line flow in water with respect to air was < 5%. WF for pots with hydraulic head was also in the order air>soil>water, but with significant increase in WF. Hydraulic conductivity Ks was in the order air>soil>water.Ks in water was independent of MD, whereas for air and soil, Ks increased with MD. Thus total WF is partially under hydraulic head and partly due to pull effect through capillary pores on pot wall either due to MD in air or prevailing soil water tension in soil.

Strategic planning as communicative process

This paper examines the construction of a strategic plan as a communicative process. Drawing on Ricoeur’s concepts of decontextualization and recontextualization, we conceptualize strategic planning activities as being constituted through the iterative and recursive relationship of talk and text. Based on an in-depth case study, our findings show how multiple actors engage in a formal strategic planning process which is manifested in a written strategy document. This document is thus central in the iterative talk to text cycles. As individuals express their interpretations of the current strategic plan in talk, they are able to make amendments to the text, which then shape future textual versions of the plan. This cycle is repeated in a recursive process, in which the meanings attributed to talk and text increasingly converge within a final agreed plan. We develop our findings into a process model of the communication process that explains how texts become more authoritative over time and, in doing so, how they inscribe power relationships and social order within organizations. These findings contribute to the literature on strategic planning and on organization as a communication process.

Municipal benchmarking:organisational learning and network performance in the public sector

The main purpose of this dissertation is to assess the relation between municipal benchmarking and organisational learning with a specific emphasis on benchlearning and performance within municipalities and between groups of municipalities in the building and housing sector in the Netherlands. The first and main conclusion is that this relation exists, but that the relative success of different approaches to dimensions of change and organisational learning are a key explanatory factor for differences in the success of benchlearning. Seven other important conclusions could be derived from the empirical research. First, a combination of interpretative approaches at the group level with a mixture of hierarchical and network strategies, positively influences benchlearning. Second, interaction among professionals at the inter-organisational level strengthens benchlearning. Third, stimulating supporting factors can be seen as a more important strategy to strengthen benchlearning than pulling down barriers. Fourth, in order to facilitate benchlearning, intrinsic motivation and communication skills matter, and are supported by a high level of cooperation (i.e., team work), a flat organisational structure and interactions between individuals. Fifth, benchlearning is facilitated by a strategy that is based on a balanced use of episodic (emergent) and systemic (deliberate) forms of power. Sixth, high levels of benchlearning will be facilitated by an analyser or prospector strategic stance. Prospectors and analysers reach a different learning outcome than defenders and reactors. Whereas analysers and prospectors are willing to change policies when it is perceived as necessary, the strategic stances of defenders and reactors result in narrow process improvements (i.e., single-loop learning). Seventh, performance improvement is influenced by functional perceptions towards performance, and these perceptions ultimately influence the elements adopted. This research shows that efforts aimed at benchlearning and ultimately improved service delivery, should be directed to a multi-level and multi-dimensional approach addressing the context, content and process of dimensions of change and organisational learning.