Search

One of the priority areas of the UK healthcare system is urgent and emergency care, especially accident and emergency departments (A&E departments). Currently, there is much interest in studying the unintended consequences of the current UK healthcare performance system. Simulation modelling has been proved to be a useful tool for modelling different aspects of the healthcare systems, particularly those related to the performance of A&E departments. Most of the available literature on modelling A&E departments focus on supporting operational decision-making and planning in specific healthcare units to study particular problems such as staff scheduling, resource utilisation, and waiting time issues. That is, most simulation studies focus on analysing how different configurations of healthcare systems affect their performance. However, to our knowledge, few simulation studies focus on explaining how human behaviour affects the performance of the system, and very few have studied how, in turn, performance targets set for A&E departments affect human behaviour in healthcare systems. Some aspects of human behaviour have been incorporated within existing simulation models, though with limitations. In fact, most studies have aimed to study patients’ behaviour, and few have included some aspects of the behaviour of clinical staff. Here we consider how to model clinician behaviour in relation to the performance of A&E departments. This thesis presents an exploratory study of the use of agent-based modelling and simulation (ABMS) and discrete event simulation (DES) to demonstrate how to model clinician behaviour within an A&E department and how that behaviour is related to waiting time performance. Clinical behaviour, incorporated in the simulation models developed here, employs a framework called PECS that assumes that behaviour is influenced by Physical (P), Emotional (E), Cognitive (C) and Social (S) factors. A discussion of the advantages and limitations of the use of ABMS and DES to model such behaviour is included. The findings of this research demonstrate that ABMS is well suited to simulate human behaviour in an A&E department. However, it is not explicitly designed to model processes of complex operational and queue-based systems such as accident and emergency departments. In addition, this research work also demonstrates that DES is an adequate tool for modelling A&E’s processes and patient flows, that can, in fact, incorporate different aspects of human behaviour. Furthermore, the process of modelling human behaviour in DES is complex because, though most DES software allows the representation of reactive behaviour, they make it difficult to model other types of human behaviour The main contributions of this thesis are: 1) a comparison and evaluation of how suitable ABMS and DES are for modelling clinical behaviour, 2) an approach to model the relationship between human behaviour and waiting time performance, considering four aspects of human behaviour (physical, emotional, cognitive and social).

Aphids are phloem-feeding insects that cause severe yield losses on crops, including cereals such as barley. While most aphid species are limited to one or few host species, some are able to reproduce on many plants belonging to different families. Interestingly, aphid probing-behaviour can be observed on both host and non-host plants indicating that interactions take place at the molecular level and may impact host range. We found that the barley specialist Rhopalosiphum padi and the broad host range Myzus persicae showed differences in colonization, settlement and probing-behaviour on barley. Analyses of barley transcriptional responses revealed gene sets differentially regulated upon the different barley-aphid interactions, where M. persicae induced the most pronounced barley transcriptional response. Interestingly, we identified several genes strongly up-regulated upon interaction with M. persicae, and to a lesser extent upon R. padi interaction, including thionins and the Late Embryogenesis Abundant gene 14 (LEA14). Ectopic expression of two barley thionins in Nicotiana benthamiana reduced host susceptibility to M. persicae, potentially reflecting a role in defence against aphids. We have generated barley mutant lines, using CRISPR-Cas9 technology, to investigate its role in plant-aphid interactions. We characterized also the R. padi and M. persicae responses upon being exposed to different plant environments. We characterized the aphid probing and feeding in different host and poor-/non-host plants, revealing that plant resistance to aphids can be based in different plant cell layers. Aphids only showed limited transcriptional responses upon being moved from host plants to either a host-, poor-host/non-host plant, or to an artificial diet, and predicted aphid effector genes, essential for parasitism, were expressed regardless of the type of interaction. Focusing on aphid effectors, we characterized 4 putative orthologous effector pairs from R. padi and M. persicae with regards to their subcellular localization, expression, and contribution to plant susceptibility. We demonstrate that ectopic expression of two R. padi effectors in barley enhances plant susceptibility to R. padi but not M. persicae, highlighting the importance of these two effectors in barley colonization in an aphid species-specific manner.

Chromite ore is the raw material used in the manufacturing of ferrochromium, which is an important metallurgical product employed in the stainless-steel industry. Chromium-based chemicals have also a wide range of applications, including pigments industry, leather tanning processes and surface treatments. The production of chromium chemicals is based on the alkali roasting of chromite ore in oxidising atmosphere in order to extract chromium as water soluble alkali chromate (Na2CrO4, K2CrO4). The main drawback of this process is the inevitable generation of a hazardous processing waste containing highly toxic hexavalent chromium. This residue needs to be landfilled and presents a serious environmental concern due to the lethal effects of Cr6+ in flora and fauna. With the purpose of avoiding the formation of highly toxic Cr6+, a novel process for extraction of Cr2O3 based on the carbothermal reduction of chromite ore in the presence of alkali, is proposed. During the reductive alkali roasting (or alkali reduction) of chromite, iron is reduced to metallic form and chromium reacts with Na2O to form sodium chromite (NaCrO2). Reduced samples are subjected to wet magnetic separation obtaining a magnetic fraction rich in metallic iron and a non-magnetic fraction which contains the NaCrO2 formed. The non-magnetic fraction is further treated to extract a Cr2O3-rich product, which may be used as raw material for manufacturing of high grade Cr2O3. 85.6% Cr2O3 recovery was achieved after chromite reduction with Na2CO3 and activated charcoal (1050oC, 2.5 hours), followed by magnetic separation and leaching of the non-magnetic fraction with water and 0.5 M sulfuric acid. A final 83.6% Cr2O3-rich product was obtained. This process does not generate toxic waste in gas, liquid or solid form, as the formation of Cr6+ is completely avoided by maintaining chromium in (3+)-state at all stages of the process. The fundamentals of the different stages of the process were investigated, including the thermodynamics, kinetics and physico-chemistry of the reduction reaction as a function of the process parameters. Mass balance and energy balance, and the environmental aspects of the process were also studied based on the proposed flowsheet of the reductive alkali roasting process.

Short dysfunctional telomeres can result in chromosome fusions that drive genomic rearrangements and ultimately malignant progression. In Chronic Lymphocytic Leukaemia (CLL), telomere length (TL) is a powerful predictor of patient survival. The aim of this project is to understand the role that telomere dysfunction plays in driving the evolution of the CLL genome. Telomere fusions were detected in 71% of 276 CLL patients with short telomeres (TL < 3.81Kb). From 9 CLL patient samples with the highest fusion frequency (> 4.20 x 10-5/diploid genome), 914 telomere fusions were characterised using Illumina HiSeq paired-end sequencing. In addition to intra- and inter-chromosomal recombinations, telomere fusions with non-telomeric loci were detected, including the ancestral telomere at Chr2q13, mitochondrial DNA, and loci associated with copy number aberrations in CLL. Telomere fusions also incorporated genes expressed in CLL-B lymphocytes and other oncogenes, suggesting that active chromatin is more prone to damage and aberrant repair. These events were potentially mediated by A-NHEJ that requires microhomology. Translocations involving hTERT, proximal to the 5p telomere, have previously been detected in CLL and associated with telomerase upregulation. In this study, 5p telomere fusions were identified in 22.6% patient samples and 172 fusion events that involved 5p were characterised, which may explain mechanisms of telomerase reactivation in cancer. Surprisingly, 67% of the 9 patients presented bimodal TL distributions compared to the overall cohort (4% of 276), consistent with intra-tumour heterogeneity, which was confirmed for one patient. For this patient with indolent disease, chromosomal rearrangements were detected, in addition to a novel mutation in REV3L implicated in translesion synthesis that may negatively impact cancer cells fitness and be a potential therapeutic target. This study shows that telomere dysfunction in CLL initiates genome-wide instability providing a source for genetic variability that allows intra-tumour heterogeneity and tumour progression. However, therapeutically-exploiting this instability could prove beneficial for patient outcome.

The placenta's ability to sense the maternal environment may be necessary for adapting placental function to meet the needs of the growing fetus. The broader aim of this study was to identify mechanisms that could be involved in sensing which may act in addition to, or in conjunction with, established mechanisms such as the mTOR pathway. This was explored in two systems, a mouse model of maternal high-fat diet and metformin treatment and placentas from human cohorts. In the mouse model of maternal high-fat diet and metformin treatment, the two conditions were shown to have distinct effects on the placenta, indicating that they were acting via independent sensing pathways. RNA sequencing data demonstrated that maternal metformin treatment affected metabolic and transport pathways in the mouse placenta. To explore whether the effects of maternal metformin treatment on the placenta were direct, or mediated via effects on the mother, an in vitro model of metformin exposure was developed. Effects of metformin in vitro showed marked differences from those observed in vitro raining question about whether the effects observed in vitro were direct. Expression of the fat mass and obesity associated (FTO) gene was shown to be related to birth weight in placentas from the Southampton Women's Survey, but FTO expression was not altered in SGA babies compared to controls. To investigate whether FTO acted via regulation of microRNA, knock down experiments were performed followed by microRNA sequencing. Placental adaptation to the maternal environment is a complex process that is mediated by different sensing pathways in the placenta. Future studies need to distinguish between direct and indirect effects on the placenta and to focus on specific pathways via which signals may be mediated.

Having worked as a psychologist in both the UK and Lima, Peru, working with patients who present a variety of conditions ranging from a depression to severe cases of schizophrenia, I became concerned by the way in which patients reacted to their diagnoses and in particular by the negative response of patients diagnosed with Borderline Personality Disorder (BPD). I also perceived that the lack of a clear and accepted diagnosis caused significant confusion regarding the condition for patients, carers and professionals. This led me to question the value of the diagnoses in the process of understanding and helping people with emotional distress or psychological problems. This study is a response to my experience and the experience participants expressed through me.

The thesis examines the complex relationship between individual experiences of breast cancer and the wider social, political and discursive context in which they are located. It focuses on how Spanish women living with breast cancer define their own health priorities by exploring their experiences and their dissatisfactions, which appear to have been excluded from public and biomedical discourses. The data was collected in a provincial city in Western Spain and focused on the lived experiences of 32 women living and surviving breast cancer. Interviews were mainly conducted in the headquarters of the Spanish Association against Cancer of that region, but also at women's homes and in other public spaces. Based upon a framework of narratives of resistance, grounded in feminist theory, critical medical anthropology and sociology, an ethnographic approach allowed a focus on breast cancer patients and survivors as ‘experts' of their own health, addressing fundamental concerns in the production of knowledge. The thesis discusses the relationship between breast cancer and social inequality. It examines the dramatic ways that structures of power such as class, age, gender, and disability, intersect and “conspire” through a web of social beliefs, practices, norms and expectations to shape, and exacerbate, women's experiences of illness, in particular, of those women who need health care the most. The research also highlights the ways in which the experiential symptoms of breast cancer are portrayed and perceived in public and medical discourses in sexual terms or physiological terms, which ignores the wider social and embodied contexts of women's experiences. By answering the call made by feminist writers such as Wilkinson (2001) and Broom (2000) to listening to the narratives of resistance of these Spanish women, this study therefore offers both a particular cultural account of their collaboration with a range of institutions such as health professionals, charities, the family and the social care system, but also valuable lay experiences which are more generally relevant to wider healthcare practice and policy.

A key step in metastasis is the interaction and penetration of the vascular endothelium by cancer cells. Tight Junctions (TJ) are located between the cancer epithelial cells themselves functioning in an adhesive manner, and between the endothelial cells. They represent a critical barrier which the cancer cells must overcome in order to penetrate and initiate metastasis. The Claudin family are TJ proteins expressed in both endothelial and epithelial cells. They participate in the formation of tissue barriers between different tissue compartments by regulating the efflux of molecules through TJ complexes. This thesis examined the level of expression and distribution of Claudin-5 in human breast cancer tissues and analysed them against clinical parameters. The effect of knockdown and forced expression of Claudin-5 in the MDA-MB-231 aggressive breast cancer cell line and in the HECV human endothelial cell line was also examined. Results revealed that Claudin-5 is aberrantly expressed in human breast cancer and has a link to the clinical outcome of the patient. Patients who died from breast cancer had higher levels of Claudin-5 compared with patients who remained disease-free. Furthermore, patients whose tumours expressed high levels of Claudin-5 had shorter survival than those with low levels. Investigating in vitro the effect of altering levels of expression of Claudin-5 in MDA-MB-231and HECV cells revealed that the role of Claudin-5 was not primarily in keeping the cell barrier tight suggesting little function in the TJ of these cells, in fact a link was identified between Claudin-5 and cell motility. Furthermore, a possible link between Claudin-5 and N-WASP, and Claudin-5 and ROCK was demonstrated when interactions between these proteins were seen in both cell lines. Moreover, cell motility was assessed following treatment with N-WASP inhibitor, Arp2/3 inhibitor and ROCK inhibitor. Results show that the knockdown of Claudin-5 in HECV cells masked their response to N-WASP inhibitor, Arp2/3 inhibitor and ROCK inhibitor. A parallel response was observed in the knockdown of Claudin-5 in MDA-MB-231 after treatment with N-WASP inhibitor and Arp2/3 inhibitor however treatment with ROCK inhibitor did not reveal any differences in motility in this particular cell line. This study portrays a very new and interesting role for Claudin-5 in cell motility involving the N-WASP and ROCK signalling cascade indicating a possible role for Claudin-5 in the metastasis and progression of human breast cancer.

In the last decade London and Mexico City have suffered from perceived poor air quality due to increased concentrations of road transport emissions. Current data on mortality rates show that in 1991 a wintertime pollution episode in London contributed to 100-180 premature deaths; similarly, it is said that high levels of pollution in Mexico City during 1990 contributed to an estimated total number of 6,400 excess deaths. In addition, the number of health studies on morbidity in these two cities shows that air pollution has produced adverse effects on the health and well-being of their inhabitants. Under London and Mexico City's air quality situation local authorities play a crucial role for addressing and tackling this urban environmental problem. This thesis examines air quality management and diverse models of local government organisation. By adopting a comparative approach, the analysis focuses on how diverse local government structures operate in relation to air pollution control from the perspective of local and central authorities and other key agencies. The purpose of this research is to combine analysis of the impact of political and institutional changes for air quality management looking at two local case-studies: London and Mexico City. The main objective is to contribute to the understanding of local government studies as well as of air quality policy research. Theoretically, the research outlines the debates on reorganising local government by focusing on three perspectives which offer diverse explanations to urban environmental problems: orthodox public administration model, public choice theory, and the local governance approach. The main argument considers the need for both an upper-tier area-wide coordinating authority and lower-tier politically fragmented government units at the local level for improving air quality and thus in both urban centres.

This dissertation project examines the implementation of a critical reading intervention in a Mexican university, and the emergence of target critical reading processes in Mexican college-level EFL readers. It uses a Complexity Theory-inspired, qualitative methodology. Orienting the selection and design of materials is a deep view of culture that focuses on competing ideologies as a site of cultural production. Also orienting the pedagogical design is a goal to enable readers to infer aspects of a text's social and ideological context from deep examinations of its linguistic patterns and rhetorical strategies. The metalanguage and analytic procedures of Appraisal Theory (a subset of Systemic Functional Linguistics), Burkean rhetoric, and Toulmin analysis were used to design activities and discourse organizers aimed at promoting rhetorical inferences and ideological critique. Adapted versions of these concepts and analytic procedures were taught to students. The study focused on investigating the emergence of the target interpretive processes in the student population as well as identifying factors underlying observable student reading practices. Results from these analyses were used to inform the theorizations of learning and instruction underpinning the intervention. Findings show that previous, non-target genre and rhetorical knowledge strongly influenced some students' initial implausible interpretations of authorial attitude and audience. However, the intervention was successful in helping students to produce plausible interpretations. Genre and rhetorical knowledge thus emerged as important elements of the theorizations of learning needs and outcomes, which led to modifications in the underlying instructional theory. Students learned to use the metalanguage of Appraisal analysis and reported that it was helpful in improving comprehension. Unexpectedly, students reported the emergence of an awareness of the need to monitor their comprehension. They also showed and reported increased ability to build richer, more plausible representations of texts in general after doing Appraisal analysis. Some students also reported internalizing the learned analytic procedures and applying them to other genres. These results have implications for L1 and L2 reading pedagogy and contribute to understanding the processes involved in making rhetorical inferences and resisting ideology. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

A set of 16 aeroengine micromixing injectors were adapted from a lean direct injection of fuel concept to be operated on hydrogen, or hydrogen/natural gas blends. These come from a statistical design to study three of their main geometric factors (the air split, the fuel swirl and the air swirl), and were designed such that their effective areas were essentially the same. Collins Aerospace was in charge of the injector design and supply, targeting flows linked to a Solar Turbines industrial engine.UCICL, with the support of the Department of Energy contract DE-FE0032073, was in charge of this first screening testing at atmospheric conditions, and the next demonstration stage with a laboratory scale model combustion at higher pressures.A three-level Box-Behnken design was first employed to evaluate the lean blow-out limits of the test hardware, depending on the preheat temperature of the air flow, the air pressure drop across the airbox, and the fuel composition (in terms of the percentage of hydrogen in the hydrogen/natural gas blend). This resulted in some clear trends on the injector stability as a function of the combustion conditions, but also the injector geometry.The fuel composition was the main factor on the predicted model, being the combustion conditions with a higher hydrogen content those with a wider range of stability, because of hydrogen's higher reactivity and diffusivity. Lower pressure drops (and therefore lower air flow velocity) also enhanced the stability of the combustion, and so did lower preheat temperature levels. On the injector geometry factors, both low levels of air split and air swirl expanded the lower flammability limits, because of the reduction on the mixing with the fuel flow and therefore yielding into diffusive flames (which showed longer stability ranges, specially for hydrogen fuels).Once the stability was assessed, the so-called screening phase of the project was conducted. Again, a three-level Box-Behnken design was designed adding an extra factor to the previous three, this being the adiabatic flame temperature. Emissions and flame diagnostics were evaluated simultaneously, for the resulting testing matrix for each of the 16 injectors. The emissions data was recorded on a volumetric dry basis corrected to 15% oxygen, and then converted into a mass basis in ng/J, aligning with the most recently reported bias with the reported basis for hydrogen versus natural gas combustion.Regarding the flame structure characterization, the main focus of the current work, three different cameras were operated in parallel. A Nikon D90 was used to capture the visible spectrum of the flame, fixing its operating mode to manual with a 2.5 shutter speed and F4 aperture. An FB-N9-U Dynacolor camera, mounting a Sony CMOS sensor, was used to record the OH* chemiluminescence (in the UV spectrum), fixing its exposure time to 0.9999 seconds and electronic gain to 6 dB. Finally, a Phantom v7.1 was used to record the high-speed dynamics of the flame, with 200 frames per second as the main factor to consider.The study mainly focused on the responses extracted from the OH* chemiluminescence imaging. Because of its direct correlation with the rate of heat release, it is commonly used to characterize the flame front. These responses were, for the most part, the flame area and its average brightness, the heat release area and its center of gravity and leading edge. To assess the importance of the tested factors and their interactions, an analysis of variance was performed for each response, with significant indicators of p-values lower than 0.05. The obtained models were first evaluated against the variability of the responses, and then using the statistical parameters that the used software provided.The effect of the confinement ratio of the flame by the combustor quartz tube was also studied, since its dimensions were arbitrarily defined during the design of the setup. A reduction on its length, and next on its inner diameter, concluded that no significant change occurred on the flame structure because of it.Finally, the presented thesis concludes with the coupling of both the NOx emissions study and the imaging flame characterization. To do so, both the statistical software DesignExpert and a Random Forest machine learning algorithm were used. The latter performed significantly better than the forming, yielding into 80%-accurate predictions of the NOx emissions as a function of the injector geometry, the combustion conditions, and OH* chemiluminescence responses.This coupled study was also utilized to reaffirm the conclusions that the emissions study extracted: the injector configuration with lower nitrogen oxides emissions is such with higher levels of air split and air swirl, and lower levels of fuel swirl.

De forma intencional ou involuntária, o ser humano transporta espécies entre locais desde tempos imemoriais. No entanto, nos últimos 50 anos, o ritmo de introdução de espécies exóticas no meio natural acelerou de forma alarmante, tornando-se numa das principais causas de perda de biodiversidade. A globalização, juntamente com as alterações climáticas, a destruição de habitats, o aumento do trânsito de pessoas e o comércio, são hoje os principais responsáveis pela perda de biodiversidade a nível global, acarretando também graves prejuízos para a economia e a saúde humana.