Search

The thesis is concerned with understanding the creation and evolution of gender equality in selected novels of Jane Austen. The characters' lived experiences of home, anxiety due to the lived experience, defining and redefining home based on anxiety and their execution of gender roles is examined to understanding the process of creation of gender equality. A significant amount of research has been conducted on Austen's creation of home and its meaning to her protagonists as well as the characters' implementation of gender roles. Most of the studies focus on women from Austen's major novels with relatively lesser studies analysing the meaning of home for Austen's male protagonists or protagonists from her minor novels. Austen's portrayal of home has been analysed mostly from sexual or social perspectives. Sources of anxiety in the lived experience of home of Austen's protagonists have rarely been analysed in connection with the processes of defining home and interpreting gender roles. This research examines how coping with anxiety in the lived experience of home to define and/or redefine home and perception of gender roles creates gender equality between the protagonists in selected novels of Austen. A domestic lens is applied to analyse six characters from the major and minor mature works of Austen. The defense mechanisms of "isolation" and "undoing" defined in the Diagnostic and Statistical Manual of Mental Disorders by the American Psychological Association are used to investigate how the selected characters cope with anxiety arising from sources in the lived experience of home. The construct of Psychological Home by Sigmon, Whitcomb and Snyder is utilised to understand how the characters define home through associations with people, spaces and/or objects. The concepts of "doing gender" and "undoing gender" by Francine Deutsch are employed to study the characters' implementation of gender roles. Finally, Janet Shibley Hyde's Gender Similarities Hypothesis is applied to the selected texts to understand the creation and evolution of gender equality. The selected characters suffer from anxiety about losing their home which stems from tyrannical and/or indifferent treatment at the hands of family members, displacement and homelessness. The characters' anxiety and experiences influence the manner in which they define home as well as their understanding of gender roles. They employ defense mechanisms to cope with their anxiety until they learn to control it by creating psychological homes or havens through their fluid implementation of gender roles. The fluid interpretation of gender roles highlights similarities between the sexes and creates equality between them.

Premenstrual syndrome (PMS) is a distressing psychological and somatic disorder of unidentified aetiology occurring during the luteal phase of the menstrual cycle. This thesis includes systematic reviews of the published literature on the therapeutic effect of surgical and hormonal suppression of ovulation in the management of premenstrual disorders. Both approaches use the principle that elimination of ovulation removes premenstrual symptomatology along with its consequences. Oestrogen treatment eliminates ovulation, but the necessity for progestogen to prevent endometrial hyperplasia may limit its use. Whilst there are several published trials of the use of oestrogen to treat PMS, this is the first systematic review aiming to evaluate the effectiveness and safety of non-contraceptive oestrogen-containing preparations (oral, patch, implant and gel) in managing PMS. The use of oral contraceptives to treat PMS lies outside the scope of this review. Gonadotropin-releasing hormone (GnRH) agonists also suppress ovarian function and have been found to reduce premenstrual symptoms in virtually all studies. Hypo-oestrogenic side effects may limit their use in clinical practice. Ours is the first Cochrane systematic review of the therapeutic effectiveness of GnRH analogues (agonists and antagonists) in the management of PMS. The only existing systematic review on the topic can be considered outdated. Surgical approaches that eliminate menstruation or ovulation have been reported to treat PMS symptoms. Surgery is an important option for the management of patients with severe premenstrual disorders who have failed to respond to other treatments. However, it is uncertain whether these invasive procedures are justified by the symptomatic relief obtained. Ours is the first systematic review aiming to assess the outcomes and safety of surgical interventions in the management of PMS. To help future clinical trial design, an online survey was conducted collecting the experiences and preferences of women suffering from PMS regarding treatment options and their expectations about the need for and taking part in research studies.

Currently, the UK is challenged by two main factors in the built environment, first is the rising demand for new housing, and second, all new buildings are recommended to adhere the energy-efficient standards (like, the nearly Zero Energy Building [nZEB] and Net Zero [NZ]) to reduce the CO2 emissions in buildings. The primary aim of this research is to determine whether modern methods of construction (MMC), specifically using magnesium oxide (MgO) structural insulated panels (SIPs) in housing design, can meet the required thermal and energy efficiency. The research evaluates the carbon impact of using MgO SIPs in constructing new houses and is quantified through a detailed energy performance analysis. A real-world case study was chosen as the research methodology to compare real-world data with simulated building energy modelling conducted in the software DesignBuilder. A detached house in Heswall, Merseyside, UK, constructed from MgO SIPs in 2016, was selected as the case study for the research. The study involved collecting and monitoring 1) heating, HVAC, and domestic hot water etc., 2) temperature, and RH% data over 12 months to evaluate the energy performance under current and future weather scenarios based on the predicted acceleration of anthropogenic climate change for three test periods: 2030, 2050 and 2080. Based on real case study on site measurements were conducted, two validation procedures were conducted to validate the recorded thermal performance against the simulated results. First, during the holiday time when the building's appliances are switched off the hourly temperature calibrations were conducted by comparing the recorded indoor temperature with simulated results from DesignBuilder model by data loggers on hourly bases. Second, the energy performance for were simulated and recorded by energy loggers for 12 months and the results were compared with electricity consumption bill. Finally, to evaluate the comfort level of the SIP house, I used thermal models (including the Passivhaus summer comfort design, Schneider thermal comfort chart, and Climate Consultant) to compare the energy consumption with thermal comfort. A parametric study was conducted in DesignBuilder using measured weather files to improve the current building envelope to reduce energy consumption. Five parameters of the building envelope were evaluated. The study highlighted that potential energy reductions could be made in the window glazing type of the SIP house; The results indicated that the most effective areas of energy saving relate to the following main parametric variables: roof insulation enhancement of 60%, making the thickness of the SIP roof 277 mm, can reduce total energy consumption by 8%; exterior wall thermal enhancement can contribute a 6% of energy reduction; and window glazing type changes can contribute to the total energy reduction by 10%. Moreover, 10% reduction in the annual energy consumption could be achieved by modify the window glazing type using argon gas instead of air between the gaps in windowpanes. However, the other parameters slightly affected the overall energy reduction, indicating that the SIP fabric has excellent insulating properties that prevented heat loss and could therefore stabilise the interior temperature throughout the year with minimum energy required. Based on the weather and energy parameters used in the simulations and thermal comfort analysis, the SIP house used as a case study for the research demonstrated the potential for meeting most energy efficiency standards (such as nZEB, NZ and Passivhaus). Furthermore, the assessment results indicate that despise noticeable temperature increase in the three timelines of 2030,2050 and 2080 the SIPs house's fabric has the ability to withstand the effect of future climate change. In addition, long term monitoring of the energy used was calculated in the research by monitoring the energy used via the data loggers. Based on the annual energy consumption, the SIP house had a lower kWh/year consumption than similar households in the UK, and the energy consumption rate was further reduced by implementing the use of renewable energy on the roof. Finally, based on the results, the using MgO SIPs in the housing sector can support the creation of nZEB/NZ homes by 2050. It is recommended that MgO SIP homes are accompanied by renewable energy as a key factor in meeting nZEB/NZ standards.

Liquid crystals are unique materials exist between the solid phase and liquid phase, and in certain ranges of temperature they show different arrangements of the molecules. Depending on the amount of order in the material, there are many different types of liquid crystal states. The nematic liquid crystals are an example of a material that has no positional order but has local orientational order, this gives rise to textures (patterns in the material) that are attractive to study. Nematic liquid crystal is an example of a material that has orientational order and no long-range positional order, this gives rise to textures (patterns in the material) that are attractive to study. This thesis concerns liquid crystals in thin films and their configurations and stability. The aim of this thesis to to explore minimum energy configurations for thin liquid shells, coupled with surface energy and curvature effects. In particular we study a thin film of liquid crystal spanning two coaxial rings, where we use the energy derived in [66] for a thin nematic liquid crystal and study the nematic film within the Landau-de Gennes model which is described through the Q-tensor theory. This thesis consists of a study of two main problems. The first is the study of the equilibrium of open surfaces (with a boundary) and involves a careful derivation of natural boundary conditions associated with minimising a general surface energy. We prove a number of results about the equations and also derive a framework to study the stability of the solutions to the equilibrium by considering the incremental equations. We demonstrate this approach in some simple examples. The second main problem is a study of the equilibrium of a thin film of liquid crystal suspended between two coaxial rings. We use the results developed in the first part of the thesis to derive the equilibrium equations and boundary conditions and solve these equations numerically for a range of dimensionless parameters related to the thin film. We perform our numerical study using two different, but related, parameterisations of the order tensor. We specialise to consider axisymmetric solutions. Finally we study the stability of the isotropic distribution (state) on a fixed catenoidal geometry, we demonstrate the emergence of defects of charge -1/2 at the onset of nematic order. We study the nonlinear equations numerically using a nonlinear Jacobi iteration.

Language is an important symbol of status and class differentiation in Pakistan. Punjabi, the mother-tongue of majority of the people in Pakistan, is considered to have an association with the uneducated working class of the country. Extant research on attitudes towards Punjabi has revealed the neglected status of Punjabi in Pakistan (Akram and Yasmeen, 2011; Rahman, 2007 & 1999; Gilani, 2014; Nazir et. Al, 2013; Sani, 2014). Language shift concerns have been reported in the majority of the previous studies and ascribed to parents' negative disposition towards Punjabi (Shackle,1970; Baart, 2003; Zaidi, 2001; Mansoor, 1993 & 2004). However, the focus of research in Pakistan, to date, has been on identifying the attitudes of urban and educated Punjabi youth only (Abbas et al., 2019; Abbas and Iqbal, 2018; Shah and Anwar, 2015; Mansoor, 1993; Riaz, 2011; Kazim and Shah, 2015; Akram and Yasmeen, 2011 and Gilani, 2014). No previous study has investigated the linguistic attitudes of less-educated Punjabis in rural and informal settings where Punjabi is most commonly spoken. The extant literature on language attitude studies in Pakistan has also paid scant attention to the notion of implicit and explicit attitudes. The present study understands 'implicit' attitude as the result of directly expressed (rather than necessarily unconscious) attitude and investigates the directly and indirectly expressed language attitudes of less-educated Pakistani Punjabis towards Punjabi in rural and informal settings. The study also aims to explore the differences/similarities between directly expressed (explicit) and indirectly expressed (implicit) attitudes. Questionnaires are employed (as a direct method) to measure the explicit attitudes of the participants, and semi-structured interviews are employed (as an indirect method) to measure respondents' implicit attitudes. 106 participants took part in the language attitude survey. 102 respondents participated in the subjective vitality survey and 31 participants were interviewed for qualitative study. The findings show that participants' explicitly expressed (explicit) attitudes are more positively inclined towards Punjabi than their indirectly expressed (implicit) attitudes towards the language, which appear to be negative. The participants seem to acknowledge the fact that Punjabi is their mother-tongue and is part of their identity, but the data indicates a lack of intergenerational transmission of Punjabi. Punjabis are not teaching their language to their children which not only suggests their negative implicitly expressed attitudes towards Punjabi, but also signals a language shift from Punjabi to Urdu. Similarly, despite explicitly reporting that Punjabi is important for maintaining a high social status, participants seem to associate Punjabi with low social status, illiteracy and backwardness. These results, therefore, indicate that there is a divergence between the explicitly and implicitly expressed attitudes of the participants towards Punjabi. This investigation enables the researcher to obtain a clear understanding of participants' social perceptions, language preferences and the status, value and importance (i.e. the vitality) of Punjabi in Pakistan. The thesis makes a significant contribution to the study of language attitude and is methodologically innovative in distinguishing between explicitly and implicitly expressed attitude.

Malware has evolved from viruses attacking single victims to more sophisticated malware with disruptive purposes. For example, WannaCry ransomware attacks led to hundreds of disruption to NHS care in 2017. Although organizations might have invested in security technologies, their susceptibility to WannaCry hints that the problem goes beyond technology. Security Operations Centres (SOCs) are the first-line of defence in an organisation, providing 24/7 monitoring, detection, and response to security attacks. This thesis aims to explore the challenges in malware detection in Security Operation Centres (SOCs) providing recommendations for possible technological solutions. We first start by investigating the workflow SOC practitioners follow. Through semi-structured interviews, we recognise the analysts' role in the SOC and their interactions with the technological solutions for malware monitoring, detection, investigation and response. Our results highlight the overwhelming reliance on analysts throughout the SOC operations, which might benefit from automation. We elicit the analysts analytical thinking when making decisions, identifying the influential factors that might impact their decision making. Moreover, we investigate security practitioners' perspectives of the security monitoring tools deployed in SOCs and their perception of the high false-positive rates. By identifying the weaknesses and strengths in current SOC tools and challenges in deploying network-monitoring tools, we derive recommendations for future SOC tools development. Understanding the type of malware is an essential step in determining the best response. Sometimes getting access to the infected host is not possible and analysts refer to the network traffic for analysis. Hence, we propose a system that classifies network flow sequences to a malware family. The proposed system is privacy-preserving and effective in classifying a binary to a malware family based on its network traffic, not requiring access to the malware binary itself. Behavioural malware detection approaches are found to be the most reliable by analysts. We propose a behaviour-based malware detection system that improves over state-of-the-art by detecting new or unseen malware. The system uses behavioural high-level network features preserving the privacy of the monitored hosts. Using this system, malware's network activities are captured and modelled as a Markov Chain. Due to the modeling of general bot network behavior by the Markov Chains, the system can detect new malware that has not been seen before making it robust against malware evolution. The novelty of this research is to provide a systematic study on SOCs processes, people, and technology; providing researchers with an understanding of the challenges and opportunities within; bridging that knowledge gap and thereby setting a better foundation for future research in the field.

Alzheimer's disease (AD) is the most common type of dementia associated with a progressive decline in cognitive function, amyloid plaque deposition and neurofibrillary tangle formation. Oligomeric forms of the amyloid-beta peptide (A-beta-o) are considered the initiating trigger which cause synaptotoxicity leading to an impairment in memory. Although many preclinical animal models of AD exist, they often only mimic acute, short-term effects of A-beta-o. Their main limitation is their inadequate replication of the progressiveness of AD. This project aims to assess the usefulness of 2-dimensional and 3-dimensional amyloid-secreting cellular systems in the development of a novel preclinical in vivo model for AD research. Formulation of a biocompatible delivery system allows the sustained secretion of A-beta-o for use in developing rodent models of chronic, sporadic AD. Chinese hamster ovary (CHO) cells expressing the human amyloid precursor protein gene (named 7PA2 cells) and wild-type cells were cultured in standard 2D conditions and conditioned media (CM) was analysed using ELISA, dot blot and westerns. A-beta-o from 7PA2 cells were injected into the hippocampus of adult female rats. A novel object recognition (NOR) task and a Y-maze test were performed to assess cognitive deficits. Brains were collected and synaptic markers analysed using western analysis. 7PA2 cells consistently secreted A-beta 1-42 over time. Prefibrillar oligomeric A-beta (~48 kDa) was secreted into the CM. Rats injected with 7PA2 CM showed progressive deficits in NOR starting at Day 4, becoming significant at Day 7 and remaining persistent at Day 14. Deficits were observed in the Y-maze at Day 8. Synaptic dysregulation accompanied cognitive decline as seen in a reduction in post-synaptic marker PSD-95, increase in pre-synaptic marker SNAP-25 and a decrease in parvalbumin compared with controls. Cell encapsulation in alginate was optimised by altering fabrication parameters (flow rate, electrostatic potential and vibration frequency). In conclusion, bioengineered 3D cellular systems encapsulating A-beta-o-secreting cells in an alginate microbead were found to be successful in their potential to model chronic A-beta secretion. Future engraftment of microbeads in the rat brain will allow the assessment of chronic A-beta deposition on cognition and pathology to better model aspects of sporadic AD.

Background: Patients receiving haemodialysis (HD) experience substantial symptom burden. These symptoms are associated with reduced physical function, poor treatment tolerance and impaired health-related quality of life. These symptoms are complex and are often undetected by individuals or health care providers (HCPs). A number of symptoms, including fatigue and depression, are associated with poor patient health, increased risk of hospitalisation and mortality. Physical and emotional symptoms are often not diagnosed or treated; however, patients often use a variety of self-management strategies to meet the challenges of these symptoms. There is a lack of knowledge regarding symptom burden and the experiences of patients receiving HD and their caregivers, particularly in Saudi Arabia. Therefore, this study aimed to explore symptom burden, the factors predicting symptoms and the self-management strategies in patients undergoing HD. It also aimed to assess the level of burden in the caregivers of these patients, the relationship between patient and caregiver burden, and the factors that may influence the reported level of caregiver burden. Method: The study used a mixed-methods, sequential, explanatory design drawing on the three concepts (influencing factors, symptoms experience, and consequences) of the Theory of Unpleasant Symptoms (TOUS) to explore symptoms burden and identify its relationships with influencing factors and consequences. Phase 1 involved a cross-sectional study design, with a convenience sample of 141 patients, who were recruited in King Khaled hospital, Saudi Arabia. Thirty-two physical and psychological symptoms were measured using the Chronic Kidney Disease-Symptom Burden Index (CKD-SBI). Additionally, 61 caregivers completed the Arabic version of the Zarit Burden Interview (ZBI-22), where 0 indicated low caregiver burden and 88 indicated severe burden, to identify the level of burden in the caregivers of patients on maintenance HD. Phase 2 of the study was a qualitative descriptive design, involving semistructural interviews, with 13 eligible patients currently receiving HD. The selection of patients for interview was based on each patients’ total CKD-SBI score, with individuals recruited from the lowest, median and highest percentiles. Additionally, 9 caregivers of these patients were also recruited and interviewed. Results: The mean age of patients was 53 ± 17 years, while caregiver’s tended to be younger, with a mean age of 36 ± 13 years. 76 (54%) of patients were male and 65 (46%) were female. The majority of caregivers were female (n= 48, 79%) and 90% (n=55) of caregivers lived with the care recipient. Of the 32 measured symptoms, patients reported having a mean of 10 ± 5. The most prevalent symptoms reported were fatigue (72%), followed by itching (63%), bone pain (62%), and muscle cramps (61%). Being female, unmarried, and having one or more health conditions demonstrated a statistically significant association with increased symptom burden in patients receiving HD. The duration of dialysis and travel time to receive dialysis was not found to be associated with symptom burden. The mean total caregiver burden scores reported by caregivers was 22 ±14. Caregiver burden was positively associated with being older and female, but not with cohabiting with the patient. Cultural beliefs and religion had a significant impact on the levels of reported symptoms, as well as reported caregiver burden. The study also found a positive correlation between the total number of symptom (symptom prevalence), in patients receiving HD and caregiver burden. Three overarching themes were revealed from patient interviews, the holistic impact of symptom burden, factors influencing symptoms and symptom management. For caregivers of patients receiving HD, three themes were identified in caregiver interviews: positive caregiving experiences, factors influencing caregiver experience and negative caregiving experiences. Discussion: This is the first study which explores the experience of symptoms and the impact of symptoms on patients receiving HD in Saudi Arabia. The process of integration between the quantitative and qualitative phases of the study, demonstrated different levels of agreement and understanding of symptoms in patients undergoing HD and burden in caregivers. In conclusion, future research should consider symptom assessment, effective patient care and the promotion of appropriate symptom management in patients receiving HD. HCPs need to be aware of the interrelation between symptom, which increase symptom burden. A reduction in symptom burden in patients with HD and other chronic illnesses may be achieved if policy makers and clinical staff focus on groups of symptoms and target the main influencing symptom. Early recognition and determining the people at high-risk of experiencing greater symptom burden needs to be undertaken to avoid its impact on patients life and enable early management and referral.

When students embark on their higher education journey, it can be a challenging time for them as they learn to foster relationships with faculty and their fellow peers. It can also be a difficult time for them as they negotiate and learn to become accustomed to the expectations of the new academic community they are joining. Most existing research on student transition stems from North America, Australia and the United Kingdom but there is limited study on the United Arab Emirates. This study therefore aimed to address this gap in literature by exploring the Emirati student experience of academic transition during their first year. It was carried out as a case study using a mixed-method sequential exploratory design where qualitative data was collected from 20 semi-structured interviews while survey questions were used to collect quantitative data from 377 first-year Emirati students. Bridges transition theory was used as a framework to explain the overlapping phases of transition.

The overarching aim of this thesis is to investigate readers' perceptions of the understandability of three translations of the Qur'an. Despite a long debate among translation theorists as to whether translations should be word-for-word or sense-for-sense, it is generally recommended that translators stick closely to the letter of the original texts when translating sacred or canonical texts. However, the translated texts need to be understandable to the reader. Functional approaches (Reiss and Vermeer's (1984) skopos theory) highlight this aspect of translation. The present research study focuses on the extent to which translations of the Qur'an are perceived as understandable by different groups of readers (people from the UK, people from India and Jordan, Muslim, and non-Muslim). No previous study has identified exactly what makes the translated text understandable in an explicitly linguistic way. The thesis is original in focusing particularly on lexical selection and archaisms, and was conducted in two phases. In the first phase of this study, the three translations were compared and analysed. The comparison was based on the lexical stylistic choices made in the three translations of the Chapter of Joseph. In the second phase of this study, an essentially quantitative method was used. The study breaks new ground by taking a questionnaire approach, eliciting reactions from readers of the Qur'an and identifying the effects of different English lexical choices and archaisms on their understanding of the translations. The following key research questions articulate the main purpose of this study: RQ1. To what extent does the stylistic variation in different English translations of a word in an Arabic verse affect the perceived understandability of the word and/or the translated text of the Qur'an? RQ2. To what extent are archaic expressions, such as verily or behold preferred by different readers of English (people from the UK, people from India and Jordan, Muslim, and non-Muslim) in the translations of the Qur'an? RQ3. Which of the different lexical styles - e.g. archaic, formal, literary, old-fashioned - associated with particular words contributes to a more positive perception of the understandability of the translated texts of the Qur'an? RQ4. Are there differences in the perception of understandability across the four groups; people from the UK, India and Jordan, Muslims, and non-Muslims? The main contributions to knowledge of this study are firstly, by adopting a reader-response questionnaire approach as a main method in translation studies to investigate the understandability of translated texts from a linguistic perspective; secondly this study contributes to knowledge by highlighting the skopos, i.e. the purpose of religious translations from the perspective of skopos theory. That is to say that religious translated texts need to be perceived as understandable by the target readers. The findings of this study revealed that different stylistic choices of words have different effects on the way translated texts are perceived as understandable, and low-frequency words were perceived as less understandable than high-frequency words by the participants. It was also found out that the perceived understandability of low frequency words, words from different lexical styles, and archaic terms differs among different readers (people from the UK, people from India and Jordan, Muslim) and also that these different groups have different stylistic preferences. Based on the study, reader-response theory and skopos theory can put forward a new perspective for religious translation, and provide a modern account around the language of religious translations. They can also inform the choice of words which contribute to a positive perception of understandability. These choices can be used as a reference for future religious translations (see section 5.3 and chapter 6).

Recurrent airway infection and its complications are the leading cause of death in Cystic Fibrosis (CF) but remain poorly understood. Molecular microbiology demonstrates that the CF airways are more polymicrobial than previously thought. The role of the microbiota in disease prognosis is unclear. There have been few longitudinal studies of the airway microbiota in children, partly because sampling the lower airways is difficult as many children cannot expectorate. Part one of this thesis determined whether upper airway samples could act as surrogates for the lower airway microbiota in children. Cough swabs [CS], throat swabs [TS] and lower airway samples (bronchoalveolar lavage and bronchial brushings) were collected for 16S rRNA gene sequencing. There was good correlation between TS and the lower airways at a community but not an individual level; TS distinguished disease differences, suggesting that they could be used in longitudinal studies of the airway microbiota in children. CS sequenced poorly, thus precluding their use for molecular microbiology. The longitudinal study had two arms; infants with CF diagnosed on newborn screening (NBS), in whom molecular microbiology revealed a small increase in diversity of the airway microbiota until 2 years of age; Streptococcus spp. and Haemophilus spp. were the most common organisms and showed an inverse relationship in their relative abundances over time. The second compared older children with CF with Primary Ciliary Dyskinesia (PCD), which shares a similar pathology to CF but rarely the same rate of disease progression. This revealed similar trends to those seen in NBS in the relative abundance of Streptococcus spp. and Haemophilus spp. in PCD but not in CF. This suggests that early changes in CF mirror those seen in later childhood in PCD and a switch occurs in CF during childhood from a milder to a more pathological community composition.

Rgg is a group of transcriptional regulators found in Gram positive bacteria, and they play diverse roles including in metabolism and virulence in a range of bacteria. However, their roles in the important human pathogen Streptococcus pneumoniae are not known in detail. To assess the functional importance of Rgg homologs in S. pneumoniae, targeted mutation was used for the deletion of two rgg genes, SPD_0999 and SPD_1518 (rgg0999 and rgg1518). In vitro analysis showed that under microaerobic conditions, the mutants were attenuated on mannose and galactose compared to the wild type, whereas their growth profiles were similar to that of wild type in BHI (Brain Heart Infusion) and CDM (Chemically Defined Medium) containing glucose. In vivo analysis of Rgg mutants showed that both SPD_0999 and SPD_1518 are required for pneumococcal virulence. All mice infected intranasaly with either Rgg mutant survived significantly longer and had less bacteria in their blood compared to the wild type. Moreover, microarray analysis using cultures grown on galactose and mannose showed that the largest number of differentially expressed genes in rgg mutant strains was seen on galactose, especially those encoding for essential physiological functions and virulence related genes such as the capsular locus. Electrophoretic mobility shift assay, and transcriptional lacZ-fusions are the most appropriate techniques used for investigating the regulating role of genes in transcriptional regulation. In this study, the results show that Rgg1518 has a direct ability to control the transcription of capsule locus genes (SPD_0315-SPD_0328) and the data also show that the protein Rgg1518 acts as an activator for capsule locus genes in presence of galactose. Therefore, so far the available results show that Rggs encoded by SPD_0999 or SPD_1518 play a major role in pneumococcal virulence.

Low fertility is a major cause of lost productivity in the cattle industry. In addition, cattle provide a convenient model to study ovarian physiology in monovular species including humans. Our previous microarray studies in the bovine ovary showed the upregulation of two clusters, miR-212-132 and miR-183-96-182, in luteal relative to follicular tissues. The studies in this thesis were aimed at establishing the functional involvement of these miRNAs during the follicle-luteal transition using a bovine model as well as human tissues. The aim of the first study was to characterise the expression of miR-132 and miR-96 within luteal tissue using ISH and FACS. The expression of miR-132 was detected in most luteal compartments while miR-96 was not detectable using ISH. Further examination using FACS showed that miR-212-132 expression remained unchanged in sorted endothelia (CD144+) and steroidogenic (CD144-Nile Red (NR) +) cell fractions. In contrast, expression of miR-183 and miR-96 was significantly increased in CD144+ compared to CD144-NR+ fractions. To elucidate potential roles of these miRNAs in the CL, I used existing online databases to identify putative miRNA targets. I identified 3042 predicted bovine gene targets of these miRNAs as well as 174 miRNA targets that had been experimentally validated in human, mouse and/or rat. I also identified putatively targeted signalling pathways primarily involved in cell survival, proliferation and differentiation. For further investigation, I narrowed my list of targets to FOXO1 and ADCY6, the expression of which was naturally down- regulated during luteinisation. The second study used an in vitro model of bovine granulosa cell luteinisation. Levels of miR-183-96-182 and miR-212-132 increased significantly (P < 0.05) during the first 4 days of luteinisation in vitro. The function of miR-132 and miR-96 during luteinisation in vitro was studied. Transfection of bovine granulosa cells with specific miRNA inhibitors or mimics of miR-132 and miR-96 led, respectively, to abolished expression and a significant increase in the levels of these miRNAs (P < 0.01) within 4 days. These changes in miRNA levels did not have any effect on transcript levels of the predicted mRNA targets, FOXO1 and ADCY6, during luteinisation. However, progesterone production by luteinising granulosa cells decreased (P < 0.05) on day 2 after transfection with miR-132 inhibitor. The results demonstrated that putative miRNA target genes remained unchanged during in vitro luteinisation which was not consistent with in vivo results. The third study aimed to elucidate the effect of miRNA inhibition in bovine luteal cells in culture. The loss of miR-132 led to an increase (P < 0.05) in FOXO1 transcript but not protein levels. In contrast, inhibition of miR-96 increased protein but not transcript levels of FOXO1. Moreover, miR-96 inhibition induced an increase in the caspase 3/7 response of luteal cells to serum deprivation indicating an anti-apoptotic effect of this miRNA on these cells. In the fourth study, I investigated the role of miR-132 and miR-96 in human luteinised granulosa cells obtained from IVF patients. The levels of FOXO1 protein were significantly increased following depletion of miR-132 and miR-96, whereas caspase3/7 increased in response to miR-96 inhibition, regardless of whether cells had been serum deprived or not. Similarly, using Annexin V and Trypan blue staining an increase in numbers of apoptotic cells was observed in response to miR- 96 inhibition. In addition, reduction of FOXO1 with the siRNA inhibited the apoptotic effect of miR-96 inhibition. Interestingly, inhibition of pooled miR-132 and miR-96 reduced progesterone secretion. However, this effect was prevented by transfecting cells with FOXO1 siRNA. These results suggest that the effects of these miRNAs on cell survival and progesterone production are mediated through targeting FOXO1. In summary, my results identify miR-96 and miR-132 as potentially critical factors in ensuring luteal cell survival and steroidogenesis in both cattle and human.

We consider two cases of solid skeleton of porous materials: fixed skeleton saturated with fluid in motion and deformed skeleton. In the first case, we study a problem involving the onset of thermosolutal convection in a fluid saturated porous media when the solute concentration is subject to a chemical reaction in which the solubility of the dissolved mineral is a function of temperature, particularly the effect of a reaction rate on the stability of the systems. We consider the Darcy model, the Brinkman model, and the Darcy model with anisotropic permeability and thermal diffusivity. Moreover, in all models the systems are subjected to heat on the lower boundary and salt on the upper or lower boundary. In chapter 2 we show that the solutions to the Darcy and the Brinkman thermosolutal convection depend continuously on the reaction term when the chemical equilibrium is a linear function in temperature by establishing a priori bounds. While in chapter 3 we show continuous dependence of the solution to the Brinkman thermosolutal convection on reaction using a priori bounds for the solution when the chemical equilibrium function is an arbitrary function of temperature. In chapter 4 we investigate the effect of the reaction terms on the onset of stability in a Darcy type porous medium using the energy method. We use the D^2 Chebyshev Tau technique to solve the associated system of equations and the corresponding boundary conditions. We obtain the energy stability boundaries for different values of the reaction terms and compare them with the linear instability boundaries obtained by Pritchard & Richardson(2007). We find that the two boundaries do not coincide when there is reaction and a region of potential sub-critical instability occur. In chapter 5 we use the energy method to obtain the non-linear stability boundaries for thermosolutal convection porous medium of a Brinkman type with reaction. We implement the compound matrix technique to solve the associated system of equations with the corresponding boundary conditions. We compare the non-linear stability boundaries for different values of the reaction terms and the Brinkman coefficient with the relevant linear instability boundaries obtained by Wang & Tan(2009). Our investigation shows that a region of potential sub-critical instability may appear as we increase the reaction rate. We study the effect of the mechanical anisotropy parameter and the thermal anisotropy parameter on the stability of a Darcy reactive thermosolutal porous medium in chapter 6 using the energy method. Particularly, we restrict consideration to horizontal isotropy in mechanical and thermal properties of the porous skeleton. We find that the anisotropic permeability has opposite effect to that of the thermal anisotropy parameter on the stability on the system. In the second case, deformed solid skeleton, we study wave motion in elastic materials of double porosity structure. In chapter 7 we derive the amplitude and describe the behaviour of a one-dimensional acceleration wave based on an internal strain energy function. The overall situation is complicated as a wave moves in a three-dimensional body, therefore in chapter 8 we investigate the propagation of an acceleration wave in three-dimensional fully non-linear model.

Background: Prostate cancer is the most common cancer in men in the UK and the sixth-fastest increasing cancer in males. Within England survival rates are improving, however, these are comparatively poorer than other countries. Currently, information available on outcomes of care is scant and there is an urgent need for techniques to improve healthcare systems and processes. Aims: To provide prostate cancer pathway analysis, by applying concepts of process mining and visualisation and comparing the performance metrics against the standard pathway laid out by national guidelines. Methods: A systematic review was conducted to see how process mining has been used in healthcare. Appropriate datasets for prostate cancer were identified within Imperial College Healthcare NHS Trust London. A process model was constructed by linking and transforming cohort data from six distinct database sources. The cohort dataset was filtered to include patients who had a PSA from 2010-2015, and validated by comparing the medical patient records against a Case-note audit. Process mining techniques were applied to the data to analyse performance and conformance of the prostate cancer pathway metrics to national guideline metrics. These techniques were evaluated with stakeholders to ascertain its impact on user experience. Results: Case note audit revealed 90% match against patients found in medical records. Application of process mining techniques showed massive heterogeneity as compared to the homogenous path laid out by national guidelines. This also gave insight into bottlenecks and deviations in the pathway. Evaluation with stakeholders showed that the visualisation and technology was well accepted, high quality and recommended to be used in healthcare decision making. Conclusion: Process mining is a promising technique used to give insight into complex and flexible healthcare processes. It can map the patient journey at a local level and audit it against explicit standards of good clinical practice, which will enable us to intervene at the individual and system level to improve care.

This thesis aimed to explore the health literacy needs of South Asians, in particular reference to diabetes management. This thesis consists of two studies: 1) a survey that examines health literacy levels and 2) study two Photovoice that explore cultural perspective in daily management of diabetes and health literacy needs. In study 1 (N=350), completed a face to face survey using standardised health literacy and diabetes measures. Findings indicated the majority of participants have limited functional health literacy (61%). Findings also suggest that people with certain characteristics, such as old age, females, low socioeconomic status, and people with limited or no formal education, are at a higher risk of inadequate health literacy. In the study 2, eleven of the participants from study 1 were recruited for Photovoice project and thematic analysis of participant’s accounts and images indicated three main themes. 1)Illustration of self-management of diabetes in day-to day life, relating to personal lifestyle, capacities and skills to manage different aspects of diabetes in their daily life; 2)NHS access and utility, concerning the use of health care services in the management of diabetes. 3) Quality of life, connected with the impact of diabetes on quality of life. It has been demonstrated from study two that, despite the limited functional health literacy, participants are able to manage their diabetes and use social support in their families, the distributed resources and health literacy skills of their family members to overcome their personal limited functional capacities. The consideration of health literacy within a particular community’s cultural perspective can have the potential to maximise the assets of that community. In increasing such a level of awareness and contributing towards the evidence of health literacy as an asset approach, made it possible to use the distributed resources of the social networks and can be one strategy to improve health literacy that can reduce the health disparities in the ethnic communities.

This thesis analyses physical and soft violence in Margaret Drabble’s novels: The Radiant Way (1987), The Gate of Ivory (1991), The Red Queen: A Transcultural Tragicomedy (2004) and The Pure Gold Baby (2013) and the works of four Iraqi contemporary novelists: Hadiya Husayn’s Ma ba‘d al-hubb (2003), or Beyond Love (2012), Ahmad Sa‘dawi's Frankenstein in Baghdad (2013), Lutfiya al-Dulaymi’s Saturn Ladies: A Tale of People and a City (2009) and Aliya Mamduh’s al-mahbubat (2003) or The Loved Ones (2006). The novels are paired thematically to explore the similarities and differences in the texts, and explore how writers from different countries and traditions engage with history and view their societies in terms of historical change and the development of their respective nations. Comparing Drabble to these different novels demonstrates how much they have in common as far as the theme of violence is concerned. The thesis demonstrates how the writers explore the effects of women's submission to and rebellion against violence and their depiction of how women suffer explicit and implicit violence in male-dominated societies in secrecy. The work argues that physical and soft violence are interwoven and interconnected. So, where there is physical violence, there is nearly always soft violence and, though to a lesser extent, vice versa. Thus, soft violence can cause just as much damage, psychologically or literally, as hard violence. This work is important because it is the first attempt at comparing Margaret Drabble to key contemporary Iraqi authors, especially when two of the novels under study are still extant in Arabic only. In addition, comparative cross-cultural studies of modern English and Arabic ficton are currently rare, so this study hopes to stimulate for further studies in this field in the future.

Food waste, a global concern for several years, has gained attention from Human-Computer Interaction (HCI) research that aims to promote more sustainable lifestyles. Many researchers believe that domestic food waste is influenced by consumer behaviors that are promoted during everyday practices. The research described in this thesis starts with an investigation into the factors that influence consumer decision-making in ways that leads to food waste. The investigation was conducted using a combination of structured interviews, automatic collection of images from participants’ fridges, and Wizard-of-Oz interventions. The four causal variables of VBN theory are used throughout the thesis to structure and analyze data. These four variables are attitudinal factors, personal capabilities, contextual forces and habits or routines. The most significant of these factors, leading to the greatest amount of domestic food waste, is lack of awareness of fridge contents. This is addressed by building an effective context-aware persuasive technology. In an initial experiment, the design and implementation of a first prototype is proposed to investigate the impact of the context-aware persuasive technology system on behavior change and decision-making process. The findings indicated that availability of information about fridge contents was not in itself sufficient to persuade users to develop new habits or routines, and that contextual forces such as a busy lifestyle meant that users did not in fact enhance their personal capabilities by accessing the information about fridge contents, and that their old habits remained entrenched. These findings informed the design of an improved second prototype, called ‘EyeFridge’. This prototype has the novel functionality of pushing information over to users through notifications and reminders. A Wizard-of-Oz investigation allowed the effectiveness of these interventions to be studied without the need to build a fully functional intelligent fridge. The findings indicate that notifications and reminders overcame contextual forces and enhanced participants’ personal capabilities (by adding to their knowledge of fridge contents) so that they developed new habits or routines. Therefore, changed consumer behavior and influenced decision-making process related to food practices.

This thesis consists of a portfolio of 10 compositions accompanied by a written commentary with audio and video recordings of my works. These compositions span a wide variety of instrumentations from large orchestral works to solo instrumental works, of both Western and Eastern traditions, as well as vocal and live art installation pieces. Throughout the commentary I explore the continuum of how Eastern traditional idioms and Western art music play a role in the creation of my musical language. This includes an overview of the history of bi-cultural integration and an exploration of the motivations for integrating musics, both in my own work and that of other composers. I explore particular parameters within my works, focusing on the spectrums between composition and improvisation, the concepts of translation and transcription and collaborative practice with Western classical and musicians of Eastern traditional music. Additionally, I examine how my application of Eastern musical parameters and techniques are filtered through four of my other interests and influences: namely, my development of a gestural and timbral language which stems from an engagement with my approach to pitch and harmony.

The correct identification of body-fluid samples such as blood, semen and saliva is an integral part of the forensic analysis, which determines the course of downstream genetic analysis. Body-fluid samples are routinely found to be affected by local environmental insults such as UV radiation, high temperatures and humidity, compromising the quality of the samples and the DNA profiles generated. This problem can be exacerbated when the environmental conditions are harsh. It is widely understood that environmental insults affect the efficacy of presumptive and confirmatory tests and can have a direct impact on the quality and quantity of amplifiable DNA present. However, little published data exists detailing the empirical effects of environmental insults on presumptive and confirmatory tests. Some studies have assessed the persistence of DNA in biological samples, but none of the published research was based in environments that are routinely exposed to extremely high temperature and UV irradiation. To understand the impact of the environment data were collected from the Police Forensic DNA Unit in Ras Al Khaimah, in the United Arab Emirates. Analysis of forensic samples received from the year 2012 to 2014 identified items containing body-fluids to constitute over 95% of the total casework samples. The success rate of obtaining STR genetic profiles from these body-fluid samples was assessed: over 80% of blood samples generated full STR profiles, whereas 71.8% of semen and 46% of saliva samples resulted in full STR profiles. This was comparable to data published in the literature and illustrated the potential impact of environmental insult on body fluids, especially saliva. However, data were not available to investigate why particular samples had failed and so the effect of the environment in leading to failed profiles could only be inferred. In order to get a better understanding of the impact of the environment a series of experiments have been undertaken to empirically investigate the effect of the local environment on biological fluids commonly found at crime scenes, i.e. blood, semen and saliva. Samples were deposited on cotton, glass, and metal and exposed to the environment in direct sunlight. They were then collected over a period of 51 days in the summer of 2014 at intervals of 48 to 72 hours. Each collected sample was subjected to presumptive and confirmatory tests and DNA was extracted and assessed. The four presumptive tests were: the Kastle-Mayer and Hemastix® (Bayer Diagnostics) for blood, the Phosphatesmo KM® (Macherey-Nagel) for semen and Phadebas® Tablet Test (Megal LifeSciences) for saliva. Whereas the four confirmatory tests were: the Hexagon® OBTI test (Gesellschaft fur Biochemica und Diagnostic) and the RSID™-Blood (Independent Forensics) for blood, the RSID™-Semen and the RSID™-Saliva. Before undertaking the main experiment the DNA extraction methods available were assessed so that the most appropriate method could be used. The methods used were: Chelex-100, Phenol/chlorophorm, QIAamp® DNA Investigator Kit (Qiagen), InnuPREP® forensic extraction kit (Analytikjina), the EZ1® system using the investigator card (Qiagen), the AutoMate Express™ System using the PrepFiler™ Express kit (Applied Biosystems), the Maxwell® 16 Forensic instrument with the DNA IQ™ chemistry (Promega) and the InnuPure® C16 using the innuPREP forensic DNA kit-IPC16 (Analytikjina). One-way analysis of variance (ANOVA) showed significant differences in DNA yields when comparisons of eight extraction methods were conducted on body-fluid samples (p=2.0e-16 for blood, p=5.98e-16 for semen and p=2.82e-10 for saliva samples). Pair-wise analysis using the Tukey's (HSD) test in addition to Box-plot graphical representations identified the AutoMate Express™ System and the Chelex-100 method as giving significantly higher DNA yields. However, DNA quality was compromised when extracting blood samples using the Chelex-100 (mean IPC= 39 Ct). Based on these data Chelex-100 was chosen as the optimum method, when also taking cost into consideration. To investigate the effects of the environment on the biological fluids, the sensitivity of four presumptive and four confirmatory tests were evaluated. Presumptive tests for blood and saliva were shown to be more sensitive in identifying their respective body-fluids than their counterpart confirmatory tests. However, this was not true for semen where the confirmatory RSID™-Semen test was shown to be twice as sensitive as the presumptive Phosphatesmo KM® test. In addition, all the screening tests were able to identify their respective body-fluids even when the DNA amounts present were less than recommended for STR analysis, i.e. 1 ng. Following environmental insult ANOVA analysis on the outcome of the presumptive and confirmatory tests showed that material types did not play a significant role in the identification of environmentally insulted body-fluid samples (all p-values were above 0.05). However, significant differences were observed between the presumptive and confirmatory groups for blood samples placed on either metal or cloth (p=0.004 and p=0.002 respectively), with presumptive tests detecting blood after longer period of exposure than confirmatory tests. Semen samples on cloth also showed significant differences between the presumptive and confirmatory tests conducted (p=0.008), in this case the confirmatory tests detected semen for a longer period of environmental insult. DNA persistence varied widely between different sample types. Saliva was the most susceptible to degradation, with no DNA detected after nine days. On the other hand, full STR profiles were obtained from blood samples on cloth after 51 days of exposure (2201.5 ADD) whereas partial profiles were observed from blood recovered from metal after 18 days (724.5 ADD) and glass after 30 days (1250.25 ADD). Allelic drop-outs began to appear in semen samples after 9 days (338.5 ADD) on all substrates. Comparisons of DNA quantification results between three different DNA quantification methods, Quantifiler® Human (Applied Biosystems), Quantililer® Trio (Applied Biosystems) and Quantus™ Fluorometer (Promega) showed no significant differences when applying the techniques to environmentally insulted body-fluid samples (all p-values were above 0.05). However, some differences were observed when using the Quantus™ where DNA quantities were either too high or too low such as blood on cloth (p=0.0567) and saliva on metal (P= 0.001). Environmental insults were observed to have diverse effects on both presumptive and confirmatory tests, as well as to DNA quantities available for down-stream DNA analysis. The level of these effects was more profound in the DNA quantity and quality than body-fluids presumptive and confirmatory tests, where the tests for body fluids were positive, but no DNA profile could be generated. However, an improved knowledge of the behavior of the different tests can help with the appropriate selection of screening tests, extraction techniques and accurate quantification methods will improve the recovery of valuable information which will ultimately lead to better success rate in the process of STR genetic profiling in our Forensic Unit.

The purpose of the thesis is to investigate the quality of higher education (HE) in the business colleges of the Sultanate of Oman. The need for this investigation is rooted in the necessity to upgrade the level of knowledge and skills among the graduates so that they can provide better opportunities for the prosperity of the Omani economy. The thesis takes stakeholder perspective on the quality of HE. Initially, the thesis addresses and analyses the role and impact of stakeholders and culture on the quality of HE based on a comprehensive literature review. The overall idea about the quality of HE has been integrated in a comprehensive conceptual framework to study the role and impact of stakeholders and culture. Qualitative and quantitative studies have been integrated and applied using a mixed method of research to provide an insightful understanding of the issues related to the quality of HE in Oman. To clarify the contextual specifics a chapter on Oman is presented.

This thesis investigates how identity styles operate in a non-Western cultural context. Through four papers, it both tests and extends some of the theoretical assertions made by the social constructivist approach of identity styles (Berzonsky, 2011), which proposes that people construct both ‘who they think they are' and ‘the reality in which they live', through informational, normative or diffuse-avoidant identity orientations. Although the relationship among identity styles and well-being is well established in Western literature, there is a serious dearth of similar research in non-Western cultures such as Pakistan. Western theories tend to assume the universal generalisability of identity styles and their relationship with well-being. The primary aim of this research is to test the validity of this assumption in the cultural context of Pakistan. Paper 1 systematically examines the factorial structure of the Identity Styles Inventory (ISI-5) in a Pakistani sample. In confirmatory factor analysis, normative orientation items perform relatively poorly, leading to a possibility that the conception of normative orientation is not as universal as previously assumed. Paper 2 shows that well-being is predicted positively by information orientation and negatively by diffuse-avoidant orientation in the Pakistani sample. Normative orientation remained as non-significant predictor of well-being. Identity commitment and satisfaction of identity motives partially mediate these links. Paper 3 explores the indigenous processes of identity formation through qualitative semi-structured interviews. Normative orientation is found to operate at a much more complex level than assumed previously. Participants described many different ways of being normative, making this a less automatic, mindless and effortless process in Pakistani culture than assumed previously based on Western research models. Paper 4 focuses on the construction and psychometric testing of new measures of normative orientation suitable for use with the samples from Pakistan. Together, these studies illustrate the value of using indigenous perspectives to enrich Western-based understandings of identity formation.

The dramatic increase in oropharyngeal squamous cell carcinomas (OPSCC) over the past few decades is attributable to oncogenic types of human papillomaviruses (HPV). The presence of HPV in OPSCC has important clinical significance since patients with HPV-positive OPSCC tumours have improved response to conventional therapeutic agents such as radiation and cisplatin compared to those with HPV-negative tumours. The overall aim of this study was to investigate potential mechanisms of improved therapeutic response of HPV-positive OPSCC. Following confirmation of HPV status in a panel of five HPV-positive and two HPV-negative head and neck cancer cell lines, an in vitro model of relative sensitivity to conventional therapeutic agents was established. All HPV-positive cells were more sensitive to radiation and cisplatin compared to HPV-negative cells. Stabilisation of functional p53 tumour suppressor protein was observed following treatment of HPV-positive cells to radiation and cisplatin. Attenuation of p53 in HPV-positive cells increased resistance to these agents indicating sensitivity of these cells to conventional therapeutic agents in vitro is p53- dependent. Furthermore, abrogation of the HPV oncogene E6 also caused stabilisation of p53 and slightly sensitised cells to radiation and cisplatin. The functional role of E6 was further explored by expressing this protein in p53 mutant HPV-negative cells. Interestingly, expression of E6 increased sensitivity of HPV-negative cellsto radiation and slightly to cisplatin. This study went on evaluate the response of the aforementioned panel of cells to targeted and novel therapeutic agents. By contrast to conventional therapeutic agents, HPV-positive cells were more resistant to cetuximab (an inhibitor of the Epidermal Growth Factor Receptor, EGFR) and Tumour Necrosis Factor-related Apoptosis-Inducing Ligand (TRAIL). Expression of EGFR protein in HPV-negative cell lines was consistently high whereas there was variable protein expression in HPV-positive cells; response to cetuximab corresponded to the EGFR protein levels in the latter. An inverse correlation between HPV status EGFR protein expression was also present in formalinfixed paraffin embedded OPSCC tissue samples, but EGFR protein levels did not provide additional prognostic value beyond HPV status in the study cohort. The current study provides an in vitro model of relative sensitivity in HPVpositive OPSCC and possible supportive mechanisms to explain this observation. This study also raises the possibility that HPV-positive OPSCC may be relatively resistant to EGFR-targeted and TRAIL therapies.

Introduction: Eating disorders were previously regarded as a Western culture-bound syndrome affecting only young Western women. However they have been described in the UK and in across the world. Research has highlighted the prevalence of disordered eating among South Asian females. However little is known about the process of how this comes about, and little qualitative research has been conducted in this area. This research aimed to understand the issues relating to the development and maintenance of eating disorders among South Asian females and their help seeking behavior, as well as the barriers to accessing treatment. Methods: Three main studies were carried out; two systematic reviews, a review of prevalence (study 1), a qualitative review (study 2) and a qualitative study (study 3). For study 1, the review was planned and reported with reference to MOOSE guidelines (Stroup et al 2000) for systematic reviews of observational studies. For study 2, the quality of the studies was appraised in accordance with Critical Appraisal Skills Programme Criteria (CASP 2013), qualitative research check list. For both reviews, a systematic literature search was conducted across four data basis, Psychinfo, Medline, CINAL and EMBASE. All articles were screened against inclusion/exclusion criteria. The data extracted from the selected studies was tabulated in a way that demonstrated the methodological robustness and cultural quality of each study was also reported. For the qualitative study (study 3), semi-structured interviews were carried out with three groups of participants, ten South Asian females with eating disorders, seven parents and siblings and eighteen health care professionals. Results: For study 1, thirteen studies were initially selected. Overall, these studies reported higher prevalence of Bulimia among Asian females in the UK compared to Caucasian females. Studies conducted in Pakistan and India reported a lower prevalence rate of diagnosable eating disorders than reported in Western countries. In study 2, three studies were selected. They identified important themes; cultural conflict and controlling families. In study 3, two overarching themes were identified with corresponding sub-themes; development and maintenance of eating disorders in the context of family and cultural conflict; barriers and facilitators to accessing treatment. Conclusions: Reviewed prevalence study findings highlighted a need to consider the adaptation of measuring tools, as eating disorders may present differently in different cultures, and diagnostic criteria based on Western norms may not always be appropriate. There was a lack of qualitative studies and those available were of poor quality. The main aetiology and maintenance of Eating Disorders reported by South Asian females were focused on conflict with family and culture. Seeking treatment was difficult for these women due to stigma, shame, issues of confidentiality and lack of training and understanding in cultural competence among health care professionals.

Amphotericin B (AmB) is the gold standard treatment of systemic fungal infections. It is the secondary treatment of leishmaniasis with 97% cure rate with no reported resistance. However, the only dosage form of AmB in the market is parenteral formulations as intermittent iv infusion. Sodium deoxycholate (Fungizone) was the first conventional formulation followed by several new lipid formulations since 1990 (Ablecet, Amphocil and Ambisone). These formulations were proved to be very effective, less toxic and require shorter course of therapy compared to Fungizone®. Unfortunately, all these parenteral formulations suffer from the inconvenience of intravenous (iv) administration, required hospitalization, more importantly, induce a number of side effects, and are very expensive. Therefore, the need for oral formulations of AmB is a crucial concern. During the last four decades there have been several published efforts representing different strategies in formulating oral delivery system of AmB with reduced toxicity. None of these formulations has been introduced into the market yet. In this study a novel stealth nanotechnology formulations containing AmB have been developed for an oral administration in order to improve its solubility, bioavailability an with lower toxicity. The selection of the copolymer used PEGylated poly-lactic- co- glycolic acid (PLGA-PEG) was based on the hypothesis that FDA has approved each individual component of the copolymers for oral and parenteral administrations of poorly soluble drugs. The development of these oral formulations of AmB went through several optimization steps, including method of preparation, polymer selection, stirring rate, cosolvency, pH, particle size reduction, stabilizers, surfactants, absorption enhancer, and HPLC assay for in vitro analysis. Novel oral biodegradable stealth polymeric nanoparticles have been successfully fabricated using the commercially available PLGA-PEG copolymer for AmB by emulsion diffusion method. In vitro characterizations of the lyophilized formulations showed that iv main particles size (MPS) of AmB loaded to NPs ranged from 23.8 ±4.8 to 1068± 489.8 nm. An increased stirring rate favored AmB NPs with smaller MPS. There was a significant reduction in MPS (P < 0.05) and significant increment in the drug content (P < 0.05) and the amount of drug released (P < 0.05), when AmB-NPs were prepared using the diblock copolymer PLGA–PEG with 15% PEG compared to other copolymers investigated. The addition of three emulsifying agents poly vinyl pyrrolidone (PVP), Vitamin E (TPGS) and pluronic F-68 to AmB formulations led to significant reduction in particle size and increase in drug entrapment efficiency (DEE) compared to addition of PVP alone. Fourier transform infrared spectroscopy demonstrated a successful loading of AmB to stealth PLGA– PEG copolymers. PLGA–PEG copolymer entrapment efficiency of AmB was increased up to 56.7%, with 92.7% drug yield. The physicochemical characterization done by SEM and TEM images indicate spherical particle in nanometer size in isolated and agglomerated state. The FTIR changes obtained from different AmB-NPs formulations suggesting some sort of interaction between the drug and the polymer. A simple, fast, accurate and reliable HPLC method for the in vitro investigations (drug content and drug release from the NPs) of AmB has been developed. Intra-day and inter-day variability were ≤ 6.2% with excellent linearity(R2=0.9982) and reproducibility. All tested formulations have shown slow initial release with 20% to 54% released within 24 h in phosphate buffer containing 2% sodium deoxycholate. The release rates of AmB from these formulations were best fit to the Korsmeyer–Peppas model. Therefore, a diffusion release model is the best to characterize the in vitro release of AmB from these formulations. A new selective, sensitive and precise LC MS/MS method was developed to measure AmB concentrations via electrospray ionization source with positive ionization mode. The precision and accuracy of the developed LC MS/MS method in the concentration range of 100–4000 ng/ml show no significant difference among inter- and-intra-day analysis (p > 0.05). Linearity was observed over the investigated range with correlation coefficient, R2> 0.9943 (n = 6/day). The assay was able to detect all the drug v concentrations for pharmacokinetics and bioavailability estimation after oral dosing of AmB loaded to PLGA-PEG compared to its parenteral administration in rats. AmB solutions or NPs were kept in refrigerator during the study. After PO administration AmB loaded to PLGA-PEG (C6), AmB was rapidly absorbed, distributed, and then slowly eliminated. The effect of glycyrrhizic acid (GA) as a natural absorption enhancer added during formulation or before administration was investigated. The addition of GA significantly (P<0.05) increased AmB AUC and Cmax (2 - 3 folds). There was no significant change (P=0.09) in adding GA during formulation or before administration. A tremendous improvement of AmB oral absorption in rats by > 790 % than Fungizoneis observed after GA Addition. AmB formulations have been screened for toxicity using several in vitro assays; hemolysis, antifungal activity and analysis of the cell viability by 3-(4,5dimethylthiazoly)-2,5-diphenyl-tetrazolium bromide(MTT) assay. Fungizone was used as the reference standard. AmB loaded to PLGA-PEG of the selected formulations showed a significant reduction (P< 0.05) in the in vitro hemolytic activity as compared to Fungizone. On cellular level, AmB loaded to PLGA-PEG showed a potent activity against the in vitroC. albicans with a parallel decrease in the cytotoxicity against in the in vitro tested cell lines. Additionally, no pathological abnormalities were observed in rats given iv administration of AmB protocol except after Fungizone administration. The in vivo nephrotoxicity and histopathological evaluation of AmB were performed in both rats' kidneys and liver using forty eight rats divided into eight groups after single and multiple iv administrations of 1mg/kg of the selected formulations or Fungizonefor a week. AmB induced nephrotoxicity was also estimated in these rats by measuring blood urea nitrogen and plasma creatinine (biomedical parameters). A significant (P<0.05) nephrotoxicity was observed after Fungizone® administration compared to all AmB loaded to PLGA-PEG formulations. The histopathological study of the isolated kidney tissues confirmed this finding. Furthermore, the incidence of the liver toxicity due to the selected AmB loaded PLGA-PEG formulations has been reduced significantly as investigated through in vivo analysis (histopathological and biochemical tests) in comparison with Fungizone. vi In conclusion, a successful novel AmB oral formulation with improved efficacy and bioavailability and with less toxicity to the kidney and the liver was developed. Further investigations are needed in the near future for this formulation to be in the market as an oral delivery system of AmB.