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.

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.

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.

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.

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.

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.

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.

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.

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 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’.