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Non-small cell lung cancer (NSCLC) affects 80-85% of lung cancer patients. Tyrosine kinase inhibitors (TKIs) are targeted therapies that bind to NSCLC cells with specific mutations and inhibit their growth. However, responses to these therapies generally fail due to the emergence of drug resistance and the onset of adverse events which can include; interstitial lung disease (ILD), edema, hypothyroidism, nausea and diarrhoea. Mathematical models can increase our understanding of the biological mechanisms that determine whether a tumour is likely to respond or become resistant to treatment. When combined with experimental studies, such models can provide mechanistic insight into factors which influence the evolution to resistance and how specific drugs act. They can also aid experimental design and generate testable hypotheses concerning, for example, optimal dose regimens, scheduling protocols and combination therapies. In this thesis, we develop mathematical models of tumour growth and treatment response, and use them to determine tumour-specific factors that influence drug resistance. Further, by combining the models with preclinical data, we infer the biological properties of different NSCLC cell lines and characterise their responses to different TKIs. In the first part of the thesis, we develop a mathematical model that describes the dynamics of four cell populations that differ in their levels of resistance to two TKIs. The model accounts for mutations, competition for resources and cellular interactions and is formulated as a system of time-dependent, ordinary differential equations. We use the model to show how tumour responses to TKI combinations depend on the rates at which the tumour cells mutate and proliferate. We then reformulate the model to account for stochastic effects that encapsulate the random nature of mutation events that occur with low probabilities. We find considerable variation in the predictions generated by the deterministic and stochastic modelling frameworks, highlighting the need for careful consideration of the modelling approach when predicting drug resistance and treatment response. The second part of the thesis focuses on integrating mathematical models with experimental data in order to uncover the mechanisms driving NSCLC cells' responses to TKI treatment. We develop a suite of increasingly complex models that describe in vitro cell growth data. We use parameter estimation, information criteria/goodness-of-fit metrics and parameter identifiability analysis to investigate the identifiability of the model parameters given the preclinical data and to guide model selection. We extend the selected model to describe the response of NSCLC cells to TKI treatment. While this model is structurally identifiable, the existence of practically non-identifiable model parameters given the in vitro treatment data leads to uncertainty in the predictions of hidden variables. We use synthetic data to evaluate how experimental design (i.e. what variables are measured) affects certainty in parameter estimates and to generate hypotheses about the likely mechanisms of action of TKIs on NSCLC cells. To summarise, in this thesis, we develop a series of mathematical models that increase our understanding of the biological mechanisms that drive the evolution to resistant tumours and determine tumour response to treatment. Our results highlight the benefit of theoretical approaches for distinguishing the growth dynamics of different NSCLC cell lines, providing mechanistic insight into the effects of different drugs on different cell lines and suggesting strategies for improving experimental design.

Diffusion-weighted magnetic resonance imaging (DWI) is a key neuroimaging technique. Multi b-value DWI is composed of an unknown number of exponential components which represent water movement in various compartments, notably tissue and blood vessels. The bi-exponential model, Intravoxel Incoherent Motion (IVIM), is commonly used to fit the perfusion component but does not take account of the multi-component nature of the data. In this work, a new fitting method, the Auto-Regressive Discrete Acquisition Points Transformation (ADAPT) was developed and evaluated on simulated, phantom, volunteer and clinical DWI data. ADAPT is based on the auto-regressive moving average model, making no prior assumptions about the data. ADAPT demonstrated that it could correctly identify the number of components within the diffusion signal. The ADAPT coefficients demonstrated a significant correlation with IVIM parameters and a significantly stronger correlation with cerebral blood volume derived from dynamic susceptibility contrast MRI. A reformulation of the ADAPT method allowed the IVIM parameters to be mathematically derived from the diffusion signal and demonstrated lower bias and more accuracy than currently implemented fitting methods, which are inherently biased. ADAPT provides a novel method for non-invasive determination of diffusion and perfusion biomarkers from complex tissues.

Initiated in 2014, A level curriculum reform in England was driven by the government's desire to restore academic rigour, help bridge the school-academy divide and better prepare school leavers for the world of work, university and life in society. Reform provided the opportunity to revise A level textbooks and revive their position in the resource ecology of the classroom. Previous research on geography textbooks focuses on textbook perception and use, curriculum coverage and the representation of place. Yet, there is remarkably little research with the author, rather than textbook, as the central concern. My research fills this gap. Textbook authors are an important source of data. Drawing on communities of practice and their own accumulated knowledge and expertise, authors select, organise and transform knowledge created in the parent discipline (its methods, prevailing paradigm and knowledge) and society into a format that is appropriate for use at A level. As the discipline of geography is broad and multi-paradigmatic and the process of recontextualisation is complex, my research focuses on understanding the decisions authors make about place selection and knowledge. Place was selected as it is the most central of geographical concepts and a new core unit for the revised A level subject content. This idiographic case study research elicits the views of nine authors, with data generated using questionnaires, semistructured interviews and Q-sort. The latter is currently an under-used methodology in geography education research. By exploring themes developed through reflexive thematic analysis, findings suggest that authors draw on human, social and decisional capital developed through immersion in teaching, assessment and pedagogy. Furthermore, reflective practice is seen to play a key role in the recontextualisation of knowledge, helping authors to utilise opportunities and deal with constraints experienced during the writing process.

NF-κB is a key transcription factor involved in the regulation of inflammation. The transcriptional activity of NF-κB is regulated by a number of post-translational modifications, including phosphorylation. Phosphorylation of NF-κB subunits may regulate transcription in a gene selective manner. The NF-κB p50 subunit is an important dual regulator of inflammatory responses, which can either promote or repress gene expression depending on the formation of heterodimer or homodimer complexes, respectively. Although p50 is a critical regulator of the immune system, phosphorylation of this subunit is largely understudied. In this thesis, the role of phosphorylation of NF-κB p50 on serine 80 (S80) in regulating transcriptional responses is investigated, using two human NFKB1S80A knock-in cell lines generated by CRISPR/Cas9 genome editing techniques. Transcriptomic analyses reveal a critical role for S80 in selectively regulating the expression of a subset of NF-κB target genes in response to TNFα and LPS, including pro-inflammatory chemokines and cytokines. DNA binding analyses demonstrate that S80 regulates the binding of p50 to NF-κB binding sites in a sequence-specific manner. Specifically, phosphorylation of S80 reduces the affinity of p50 for κB sites that have an adenine at the -1 position. These data indicate that p50 S80 phosphorylation predominantly regulates transcription through the p50:p65 heterodimer, where S80 phosphorylation acts in trans to limit the NF-κB mediated transcription of pro-inflammatory genes. This advances our understanding of the regulation of transcriptional programmes by the NF-ĸB p50 subunit.

Persecutory delusions are common and are associated with poor physical and mental health, wellbeing and quality of life. Anxiety has been implicated in the formation and maintenance of paranoia and is therefore a target for treatment, adopting an interventionist-causal approach. A brief cognitive behavioural therapy for psychosis (CBTp) module targeting anxiety processes, the Street Smart intervention, has produced promising results (Freeman et al., 2013). The current study delivered this intervention in a group format and assessed the feasibility and acceptability of the intervention and RCT protocol. Eighteen people with persecutory delusions were randomised to the six session group intervention or treatment as usual using a 2:1 ratio. Feasibility of the group intervention was confirmed by positive participant feedback although attendance rates were slightly lower than the specified feasibility criterion. The RCT protocol was feasible in terms of recruitment, consent and attrition rates and the assessment procedures were acceptable. The rate of eligibility was slightly lower than the specified criterion. Estimates of variance were reported to inform future studies. The feasibility RCT suggests the Street Smart group is acceptable and provides a useful interpersonal therapeutic function although suggestions regarding improved recruitment strategy should be implemented if the development and evaluation process is to progress to the next stage.

Background and Objectives: It has been suggested that reassurance seeking may play an important role in the development and maintenance of common mental health problems such as OCD and depression. We first considered the extent of reassurance seeking in depression and OCD relative to a healthy comparison group and secondly tested the hypothesis that reassurance seeking is primarily motivated by threat in those suffering from OCD and by interpersonal concerns in those suffering from depression. Methods: The frequency and intensity of reassurance seeking and the motivation for seeking reassurance was measured using the reassurance seeking questionnaire in 28 people with OCD, 18 people with depression and 29 healthy controls. Results: The OCD group sought reassurance more and at a higher intensity than both the depression group and healthy controls. For the OCD group, reassurance seeking was found to be linked to threat concern motivation. The depression group were not motivated by threat or interpersonal concerns. Conclusions: For people suffering from OCD, reassurance is motivated by threat concern. For the depression group the motivation to seek reassurance is less clear but interpersonal concern may not be a distinct motivational factor. Key words: Reassurance seeking, Obsessive-Compulsive Disorder, depression, reassurance seeking questionnaire, threat motivation, interpersonal motivation.

Cardiovascular toxicity is defined as a severe and potentially fatal adverse reaction to certain drugs. It is one of the leading causes of attrition in drug development. Cardiovascular toxicity research has primarily focused on the role of cardiomyocytes in functional and structural cardiovascular toxicity. However, there is a growing awareness that non-myocyte cells may contribute to cardiovascular toxicity. The heart is a highly vascularised organ. Endothelial cells from the heart were compared between rat and human, as well as between different vascular beds with the use of human cardiac microvascular endothelial cells (HCMECs) and human dermal microvascular endothelial cells (HDMECs). This data demonstrated ligand induced activation of EGFR-1 in HCMEC indicating the presence of functional EGFR1. Analysis of mRNA expression of EGFR1-4 revealed higher expression of both EGFR1 and EGFR2 in HCMEC compared with HDMEC. The role of EGFR-2 (Her2) in drug-induced cardiovascular toxicity was analysed with use of Herceptin® and doxorubicin treatment. Herceptin® and doxorubicin are known to induce cardiovascular toxicity in the clinic. The effect of these drugs on the endothelial tight junction barrier was tested, revealing that Herceptin® and doxorubicin are able to induce barrier perturbment and decreased barrier function in HCMEC. Herceptin® treatment had no effect on the tight junction barrier function in HDMECs. Previous work in the group has identified a role for extracellular-signal-regulated kinase 5 (ERK5) in regulation of endothelial cell survival. The role of ERK5 in endothelial tight junction regulation was investigated using small molecule inhibitors, siRNA transient gene silencing and adenoviral–mediated overexpression of ERK5 to reveal that ERK5 plays an important role in tight junction regulation and endothelial barrier function. Statins are clinically used to lower plasma LDL-cholesterol levels in patients via inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase). Simvastatin activated ERK5 in endothelial cells via a pathway requiring MEKK3 and MEK5 leading to increased tight junction formation and increased barrier function, providing a possible mechanism for the pleiotropic effects of statins on endothelial cells. Analysis of the effects of a range of anti-cancer drugs with known cardiovascular toxicity liability revealed these drugs could disrupt tight junctions and decrease barrier function. Pre-incubation with simvastatin protected the endothelial cells from drug induced perturbment of endothelial tight junction formation and the associated decrease in barrier function. The data shows the importance of drug-induced endothelial injury in cardiovascular toxicity and highlights potential for therapeutically targeting vasculature to protect against drug-induced vascular injury.

The association of violence with sex work has been widely documented within research and policy. This thesis provides a critique and development of such perspectives. Framed from a qualitative approach, it extends current research which has offered limited insight into the realities of how violence is experienced and responded to by sex workers and agencies involved in the provision of support to sex workers. In this way, the research develops beyond a presumption and narrow understanding of violence/harm in sex work to consider how sex workers and service providers experience, define, and thus construct their responses to harm. Findings from the data indicate variation amongst participants in their responses to harm associated with sex work, with experiences of violence or supporting violence and relationships and interactions between sex workers and service providers being important factors in how these responses are constructed. Both sex workers and service providers, however, recognised and understood associations of sex work with violence and victimisation, and related attempts to encourage individuals to cease or limit involvement in sex work, although this may not apply or be appropriate to all experiences of sex work and sex workers. The thesis contends that in order to gain an informed understanding of, and develop responses to, harm associated with sex work, it is important to consider the diversity of existing experiences of sex work. This should include alternative understandings and experiences of harm that are not limited to, or focused on, violence within sex work, as informed by the experiences of different sex workers. In doing so, there is the potential to better understand and accommodate a range of sex workers’ experiences, needs and interests in ways that do not impact on sex workers’ safety, or contribute to continued stigmatisation or exclusion, where some sex workers do not identify with a view of their work as harmful, or wish to exit sex work. Consequently this could aid the provision and development of services that respect and offer support where required, for different experiences of sex work amongst sex workers.

Pervasive Refusal Syndrome was introduced to the child and adolescent psychiatric literature by Lask, Britten, Kroll, Magagna and Tranter in 1991. It is not a formal diagnosis classified within the DSM-V (APA, 2013) or ICD-10 (WHO, 1994). However, it is employed clinically as a descriptive label to denote a specific constellation of symptoms. It is understood to be characterised by a profound and pervasive refusal across different domains: eating, drinking, speech, mobilisation, and personal care (Lask et al., 1991). It is reported to be accompanied with an active rejection of help, social withdrawal and school refusal (Lask et al., 1991; Thompson & Nunn, 1997). A literature review highlighted that perspectives on PRS are predominantly based on expert professional opinion; the experiences and perspectives of children and their families are underrepresented. This exploratory study aimed to address this gap in the literature by examining how parents made sense of their child being given a diagnosis of PRS and what it was like to experience their child being unwell. Furthermore it aimed to explore how parents experienced and negotiated the treatment process. Semi-structured interviews were conducted with eight participants. The data generated from the interviews was analysed using Interpretative Phenomenological Analysis. Three superordinate themes were identified and represented: parents’ perspectives and experiences of PRS and its treatment; parents’ experiences of and relationships with professionals; and the personal “journey” that parents experienced. The findings suggested that parents’ experiences and meaning making processes were delineated by stages, which reflected the trajectory of their child’s difficulties. It seemed each stage brought new experiences, understandings and challenges. This study has provided a novel contribution to the literature and has offered new insights into the diagnosis from the perspective of a parent. The implications for clinical practice and recommendations for future research are outlined.

This study focused on experiences of healthcare consultations for lesbian, gay and bisexual (LGB) people, particularly their disclosure of sexual orientation. LGB people are more at risk of certain healthcare conditions than heterosexual people; disclosing sexual orientation allows healthcare professionals to consider the most appropriate approach to treat the concerns of LGB people. Previous literature suggests that lesbians use techniques to assess the safety of a healthcare environment before choosing to disclose their sexual orientation (Hitchcock & Wilson,1992). No previous study to the author’s knowledge has explored British LGB people’s experiences of healthcare consultations. Six students between the ages of 18 and 25 from the University of Leeds were interviewed using semi-structured interviews. These were analysed using interpretative phenomenological analysis (IPA). Individual analyses are presented followed by a group analysis detailing master themes occurring across participants. These are: somewhere safe to be free, discomfort defining sexual orientation, searching for acceptance and anticipation and fear of punishment. A process of participants’ approach to healthcare consultations and disclosure of sexual orientation is presented. A combination of participants’ search for acceptance of self and anticipation and fear of punishment seemed to shape their expectations of professionals and how they approached consultations. The interactions between professionals and participants then appeared to influence the participants’ perception of the consultations and their approach future consultations. Clinical implications of this study include: increased training for healthcare professionals around lesbian, gay and bisexual issues, so that they are better able to pick up cues from LGB patients, making it easier for them to disclose sexual orientation if they so choose. By providing the conditions for LGB people to disclose, healthcare professionals are helping to ensure that their LGB patients receive the most appropriate healthcare.

Limitations in current model systems for researching bone repair have hampered the development of alternative clinical therapies. This thesis aimed to develop and validate an ex vivo rat mandible model, to investigate specific molecular and cellular processes involved in bone repair. Maintenance of cell and tissue architecture and viability was shown within mandible slices cultured for up to 21 days, both intact and fractured. Autoradiographic studies showed that resident cells were actively synthesising and secreting proteins, and cells of the osteoblast lineage were shown to survive throughout the culture period. The model was responsive to exogenously added growth factors TGF-p1 and BMP-2, with increased cellular migration / proliferation and expression of bone matrix proteins observed. A second model system, an in vitro bone slab cell culture system, demonstrated that endogenous growth factors could be released from the matrix of bone by chemicals such as EDTA, calcium hydroxide, and sodium hydroxide. Different growth factor release kinetics were observed with each treatment, and released growth factors were capable of actively influencing the behaviour of osteogenic cells. Pre-treatment of mandible slices with these chemical treatments yielded similar results, with an observed increase in cell number, proliferation, and bone matrix protein expression. The ex vivo mandible model developed within this study may represent an ideal system for investigating specific processes of bone repair, as well as a promising alternative to in vivo testing of novel clinical therapeutics.

To ignore the strategies and structures through which stories are told, this thesis contends, is to neglect a vital dimension of their politics. Narratology provides productive analytical tools to illuminate the complex and varied mechanics of narrative form, yet it also bears the traces of its structuralist origins. Its value is therefore contingent upon its continuing reformulation as an expansive, pluralist and contextualized critical discipline. Participating in this expansion, this thesis evidences the pertinence and vitality of some narratological models and the limitations of others. It opens up alternative critical possibilities by drawing upon insights within contemporary critical theory, from poststructuralist philosophy to transcultural feminism to sociolinguistics. Above all, my interventions proceed from close readings of innovative fiction by women writers hitherto all but unrepresented in, and therefore potentially subversive of, existing models: Nicole Brossard, Daphne Marlatt, Hiromi Goto, Ali Smith, Jackie Kay, Erna Brodber, Dionne Brand, Aritha van Herk. The first chapter formulates an in-between critical space where feminist and postmodernist theories of narrative intersect. It re-examines metafiction through the lens of auto(bio)graphical practice and feminist poststructuralist theories of self, and introduces the notions of folds and echoes to describe specific structural innovations. Chapter Two examines unconventional uses of second-person address and reconsiders existing narratological approaches in their light, focusing on the `push and pull of narrative' that the `you' form enacts. Chapter Three addresses the insufficient attention paid to multiply narrated novels, theorizing them as `narrative communities' and introducing terms to describe different internal relations between narrators, relations that can often be read as determinedly 'democratic'. The final chapter contests the hegemony of temporal models of narrativity by formulating a 'spatial poetics' that accounts both for how spatial structures can be agents of narrative change and for the complexity of textual constructions of space, which frequently exceed static definitions of 'setting'. Running throughout is a reconception of narrative as located not with the figure of the narrator, but in relations of intersubjectivity. The narratological criticism formulated here works towards a situated ethics of reading responsive to the politics of writing: it is engaged, relational, and ever in process.

This work details the properties of a copolymer system comprising the ethylenedioxythiophene (EDOT) and bithiophene (BT) monomers. By applying a number of characterisation techniques to various aspects of the copolymer system an insight into its behaviour during redox cycling has been gained. If a copolymer is grown from a feed solution containing two different monomers, the mole fraction of monomers in the resulting copolymer will be determined by the composition of the feed solution and the relative reactivities of the two monomers. Only a small range of feed solutions yield copolymers containing substantial amounts of both components, except for pairs of monomers having very similar reactivities X-ray Photoelectron Spectroscopy (XPS) was introduced as a technique to determine the mole fraction of monomers within a copolymer film and compared with the mole fraction of the feed solution.

Naturally occurring CD4+CD25+ regulatory T cells are thought to play an essential role in the maintenance of immunological self-tolerance by actively suppressing auto reactive T lymphocytes. Exploitation of these cells could provide novel and effective therapies for the treatment of various clinical diseases, including autoimmune diseases and cancer. However the biology surrounding these cells is complex and there are many unresolved issues, including a lack of specific markers for these cells and an incomplete understanding of the mechanism of action of these cells. The initial experiments described in this thesis attempted to identify cell surface markers that were specific to the human CD4+CD25+ regulatory T cell population. Functional assays were conducted in parallel in an attempt to identify cell surface molecules and cytokines that might be responsible for the cell-mediated suppression. The lack of identification of a specific molecule responsible for the suppressor phenotype highlights the complexity of this cell population. As these studies progressed, a new marker of CD4+CD25+ regulatory T cells was reported called FOXP3. Subsequent experiments described in these studies focussed on investigating the effects of overexpressing human FOXP3 in human T cells. A novel cotransfection system was devised whereby the gene encoding FOXP3 was cotransfected with DNA encoding a specific receptor involved in T-cell activation (chimeric receptor). The data generated showed that overexpression of FOXP3 in resting human CD4+ and CD8+ T cells resulted in a significant inhibition of subsequent T cell activation. Splice variant forms of the FOXP3 protein were also investigated and were shown to possess potent repressor activity.

Unresolved complex mixtures (UCMs) of aromatic hydrocarbons have been found in a wide range of environmental matrices at high concentrations. However, limited consideration has been given to the potential detrimental effects of the accumulation of these compounds in the marine environment. In particular, there is a need to evaluate these compounds in the light of recent evidence that points to the long term effects of oil in the marine environment. The overall aim of this work was therefore to investigate unresolved complex mixtures of aromatic hydrocarbons in the marine environment with particular emphasis on assessment of toxicity, aqueous solubility and photodegradation behaviour. A previously established link between the reduced Scope for Growth (SFG) of mussels with the concentration of 2-3 ringed aromatic hydrocarbons in mussels from petroleum impacted sites was found also to correlate well with concentrations of aromatic hydrocarbon UCMs in mussel tissues found at the same sites. This suggests that aromatic hydrocarbon UCMs or components within may be responsible for the observed effects. To determine whether an aromatic hydrocarbon UCM was capable of eliciting a toxic response in mussels, a monoaromatic UCM was isolated from a Gullfaks (North Sea) produced crude oil. At the highest nominal aqueous concentration tested, mussel feeding rate was reduced by -40 % in the 24 hour exposure period, during which the mussels accumulated a body burden similar to the body burden of monoaromatic UCM hydrocarbons in wild mussel populations, previously shown to exhibit reduced SFG. Recent studies of hydrocarbon UCM composition using chemical degradation methods have led to the proposition of alkylcyclohexyltetralins as 'average' structures for some monoaromatic UCM hydrocarbons. The aromatic hydrocarbon 7-cyclohexyl-lmethyltetralin was synthesised herein in good yield and purity. This compound reduced mussel feeding rate by 50% during the 24-hour exposure period. The aqueous solubility of a compound is an important physicochemical parameter that influences behaviour within the marine environment and is thought to be a limiting factor in the onset of measurable toxicological response. The aqueous solubilities of three 'model' aromatic UCM hydrocarbons were determined in distilled water at 25°C using a generator column set-up. The effects of salinity and temperature on aqueous solubility were also investigated. An aqueous solution comprising an aromatic UCM was also generated. Another influence on the fate of aromatic hydrocarbons in the environment is the action of sunlight (phototransformation). Therefore aqueous solutions of three model aromatic UCM hydrocarbons were exposed to light simulated under environmental conditions. The halflives of these compounds suggested that if these compounds are indeed representative of the aromatic UCM phototransformation may influence its fate in the marine environment. The results of this study have furthered knowledge on the environmental behaviour of unresolved aromatic hydrocarbons, and suggest that these compounds should be considered in the long term impacts of oil in the environment and also warrant further study. Parts of this work have been published and the author (Smith, E. L. ) was awarded the Procter and Gamble Eurorcar prize at the 3'd World Congress of the Society of Environmental Toxicology and Chemistry, 21-25 May 2000, Brighton, for the best presentation by a young scientist.

Money, rather than being “rational” or “objective,” is deeply emotional, subjective, and filled with meanings and emotions for individuals. Despite this, how young adults—who are navigating the vulnerable life course stage in a context of risk and uncertainty—perceive money and their economic conditions is less known. Additionally, these perceptions are shaped by young adults’ relationships to broader structures of capitalism, heterosexism, cissexism, and racism, making the financial lives of young adults different and unequal. This dissertation explores the perceptions of money in the life stage of young adulthood comparing LGBTQ and cisgender heterosexual young adults in three ways. First, I examine how young adults make financial decisions regarding stimulus funds during COVID-19, highlighting how expectations for the future (as hopeful or optimistic, or terrifying and insecure) shape the perception of stimulus funds. Second, I examine one of the core sources of financial support for young adults: parent-child relationships. I find that young adults have variable financial relationships with parents, with these relationships producing emotions ranging from gratitude and support, to exploitation, control, envy, and fear. Third, I examine the prevalence of financial stress in this sample of young adults, and examine the five ways that young adults cope with financial stress including: hyperfocusing, avoidance, discussing with others, developing a system, and planning for the future. In each of these chapters, I emphasize how LGBTQ young adults and young adults of color are particularly vulnerable to negative economic conditions, and negative emotions regarding finances. Through these chapters, I highlight the stratification of resources and emotions associated with those resources in young adulthood. With rising economic insecurity, a sparse social safety net, multiple economic crises in their lifetimes, and different relationships to structures of power of capitalism, cissexism, heterosexism, and racism, young adults face complex structural issues that they attempt to cope with at the level of the individual: navigating economic crises brought on by COVID-19 with stimulus funds, financial giving and receiving in relationships with parents, and ways of coping with financial stress.

Adipose tissue is a dynamic tissue involved in hormonal, immune, and metabolic processes. Although mostly studied in the context of obesity, it has become increasingly important to study adipose tissue changes in response to aging due to an increasing elderly population. Here we profiled the transcriptomic changes of aged rats in epidydimal, subcutaneous and brown adipose depots through RNA sequencing technology. Consistent with previous characterizations of aging mouse models, we observed reduced mitochondrial gene expression and increased inflammatory pathways in the epidydimal adipose tissue of aged rats. On the contrary, in the subcutaneous adipose tissue we observed a distinct transcriptomic profile from mouse models of aging. Our results show an increased mitochondrial gene expression while a decrease in inflammatory related genes suggesting a possible a possible role of the subcutaneous depot in the adaption to metabolic and immune changes associated with age. Additionally, our results suggest an increase in leukocyte infiltration and decrease in organ morphogenesis and development in brown adipose tissue of aged rats. Moreover, In Silico studies performed to assess the age-related effects on secreted factors, revealed significant changes in the expression of adipose-secreted exosome cargo that have potential for long range interaction with other organs. Thus, overall our results indicate that adipose tissue aging in rats may have some unique features. Furthermore, our data highlights the intricacies of adipose tissue and the dramatic differences between adipose depots.

The fundamental currency of life is energy. Organisms need energy to grow, to survive and to reproduce. Understanding the acquisition of energy by consumers is thus a foundational aspect of biological research. This is especially important in the modern era, as impacts of ongoing anthropogenic effects will be mediated or amplified through food webs. Here, I explore how isotopic analysis of individual amino acids – a technique new to ecological studies – can be used to trace energy flow through animal communities in modern and ancient time periods. In particular, I focus on kelp forest food webs, which are nearshore marine ecosystems highly vulnerable to human impacts. I explore how important kelp (macroalgae in family Laminariales) are as an energy source to consumers from localities as diverse as Katmai National Park, Alaska, and Antofagasta, Chile. I also examine how the ecology of an important kelp forest species, the sea otter (Enhydra lutris) has changed over time in California. Finally, I employ a biochemical perspective to identify the mechanisms driving differences among producer isotopic values. My dissertation demonstrates that amino acid isotopic measurements can be used to confidently identify kelp-derived energy in consumers across space and time. Using this, I find that across different localities and oceanographic regions, kelp is vitally important to consumers as a source of energy. My work highlights the importance of understanding energy flow through food webs, and how this knowledge can help to better protect and manage biological systems.

This qualitative thesis examines how mid-life gay and lesbian married individuals navigate the institution of marriage. Using data from 30 couples in Massachusetts collected in 2013, 9 years after marriage equality was legalized in that state, this thesis seeks to complicate previous research which overwhelmingly focuses on the positive aspects of same-sex marriage for lesbian and gay individuals, relationships, and families. The central themes that emerge in the analysis are: 1) the symbolic power of the institution of marriage, 2) the pragmatic power of the institution of marriage, 3) the rejection of the power of the institution of marriage, and 4) ambivalence with marriage. These findings contribute to understanding not only the positive but also the negative and ambivalent effects of marriage access for lesbian and gay individuals. Additionally, this research provides new insight towards the larger goal of family studies that aims at exploring the multiple meanings of and experiences of this powerful institution.

Increasing oxytocin (OT) in the central amygdala (CeA) via infusion of a selective OT agonist (Viviani et al., 2011) or optogenetic stimulation of hypothalamic neurons (Knobloch et al., 2012) reduced conditioned freezing responses. In contrast, intracerebroventricular (i.c.v.) administration of OT increased conditioned freezing responses (Toth, Neumann, & Slattery, 2012). The route of administration may account for these differences in fear responses. Specifically, i.c.v. OT may target other amygdala areas such as the basolateral amygdala (BLA), thereby increasing freezing responses. This thesis investigated CeA and BLA infusions of OT on the acquisition and extinction of context conditioned fear responses. In two experiments investigating the effects of OT on fear acquisition, rats were trained to fear a context under a drug infusion and their retention of fear assessed when drug-free. Intra-CeA and intra-BLA infusions of OT had no effect on freezing responses across the conditioning session. However, fear responses were reduced at test indicating that OT impaired the acquisition of context conditioned fear. In 8 experiments investigating the effects of OT on fear extinction, rats were trained to fear a context, their fear extinguished under a drug infusion or the drug was infused immediately after extinction and their retention of extinguished fear assessed when drug-free. Infusion of OT into the CeA impaired, whereas infusion into the BLA facilitated the extinction of fear responses. This was blocked by co-infusion of a selective OT antagonist (OTA; desGly-NH2-d(CH2)5[D-Tyr2,Thr4]OVT) suggesting OT receptor specificity. OT infused into the BLA after extinction training had no effect on fear responses at test suggesting that OT does not affect the consolidation of extinction learning in the BLA. In contrast, OT infused into the CeA after extinction training reduced fear responses at test suggesting that OT had impaired the consolidation of extinction learning in this nucleus. OTA infused into the CeA reduced freezing responses across the extinction session whereas BLA-OTA had no effect. This suggests that endogenous CeA-OT maintains freezing responses across the extinction session whereas endogenous BLA-OT may not influence fear responding or the depression of fear responses that occur across extinction training. Lastly, an infusion of muscimol into the BLA and CeA had effects similar to OT on long-term depression of fear responses suggesting that OT may influence fear extinction via an increase in GABA activity.

This thesis seeks to examine the use of sound on (and often, off-) the early modern stage. While its initial – and primary – focus is sound effects, it also explores the definition of sound itself, according to early modern understandings of the acoustic world to be found in medical manuals, sermons, and academic drama. It develops previous work on sound, such as that by Bruce Smith, Wes Folkerth, and Gina Bloom, while putting pressure on the methodologies used to understand so intangible an effect. Moreover, while existing critical studies favour Shakespeare, this thesis also hears the sounds of non-canonical plays. Chapter One explores sound effects as “soundbites” (sonic memes) and shows that sound effects can act as an allusion or create nostalgia for older plays. Chapter Two examines Jacobean drama in the light of Schaeffer’s term, ‘acousmatic’ (as used and reconsidered by Brian Kane). It shows that Jacobean playwrights concealed the sources of sound effects in order to create a frightening and uncanny atmosphere on stage. Chapter Three explores the plays of Ben Jonson and their representation of sound and the body, moving between speech and noise, lungs and instruments. It concludes that Jonson’s attempts to define and control sound while making use of sound effects are contradictory. Chapter Four suggests that Shakespeare’s use of sound was often verbal, as “phonographic” (or narrated) sound. It offers readings of “ekphrastic” speeches which describe and conjure sound that is not performed. This thesis concludes that not only are sound effects an integral unit of early modern play texts, but that attention to their use can offer fresh readings and new understandings of such plays. Blending theatre history and sensory studies, this thesis recaptures the sound of early modern drama and hears the early modern stage amidst its considerable noise.

This study focuses on the metalinguistic knowledge (MLK) of experienced Saudi teachers (ETs) and fourth year student teachers (STs) who had graduated or would graduate from a particular University in Saudi Arabia. The main aim of the study was to investigate the overall level of the participants’ MLK (including their knowledge of grammar rules and metalinguistic terms), the more specific nature of the participants’ MLK, and their perceptions of their own MLK. Moreover, the study aimed to reveal any significant differences between the two groups. The study drew on a mixed methods research approach. The quantitative data involved an MLK test and questionnaires, and the qualitative data comprised semi-structured interviews, observations and role-playing. The ET group significantly outscored the ST group on the test, demonstrating a higher level of MLK. The study showed that, for both groups, a good level of MLK at sentence level did not guarantee an ability to apply it to more complex grammar items in text. It also revealed that both groups’ receptive knowledge of rules was better that than their productive knowledge. Moreover, the teachers in both groups lacked an understanding of phrases and clauses and were poor in their ability to produce the corresponding terms. Despite this, the ETs generally displayed substantially higher levels of confidence in their overall level of MLK and all its individual components, than their actual performance on the test instrument would justify and did not seem motivated to enhance their MLK. The STs, in contrast, generally lacked confidence in their overall level of MLK, and all the related individual components, with the exception of their productive knowledge of terms. For both groups, there was a gap between their awareness of limitations and their actual knowledge. They were aware of gaps in their knowledge, but not precisely what these were.

By examining five types of astronomical and celestial phenomena—comets, constellations, the zodiac, planets, and the music of the spheres—this thesis posits not only that early modern dramatists were influenced by established and emerging natural philosophy as habits of thought that manifested in their writing, but also that astronomical phenomena operate within the drama, performance, and in the theatre as elements for creating and developing a distinctly spatial dramaturgy. Using theories from the spatial turn, this thesis maps the positions, edges, disturbances, and motions of celestial properties within the imaginary and physical space of early modern drama and theatre. It argues that the case study plays examined within this thesis demonstrate a period-wide engagement, rather than an authorial-, company-, theatre-, or even genre-specific practice. Dramatists developed techniques using astronomical phenomena as dramatic methods that occasionally underscored early modern astronomical thought. However, in many cases constructed plots, characters, visual and sound effects, and movements transgressed astronomical expectations. Dramatists broke down constellations, inserted new stars in the heavens, created zodiacal females, launched pyrotechnical comets, moved planets unexpectedly across the stage, and played (and refrained from playing) celestial "music" for the audience. Recognising composite and often contradictory astronomical constructions within the drama, this thesis moves the critical discussion away from an intellectual history of natural philosophy and gravitates toward an active astronomical dramaturgy.

The importance of parental involvement in their children’s learning are highlighted by many studies in the literature and this study attempted to increase parental involvement in their child’s science and general learning. This study includes several aims that were investigated in two stages. The first aim of this study, which investigated in Stage One was to identify the extent of parental involvement in their child’s general and science learning, and the relationships between level of involvement and parents’ backgrounds (parents, gender, child’s gender, school group, science based career, family education). The second stage included the main purpose of this study. This purpose was to investigate the effects of parents’ practising online science activities with their child intervention on parental involvement and parents’ attitudes towards science as well as children’s attitudes towards science. Parents of either public and private schools’ children from two different cities (Hatay and Gaziantep) of Southern Turkey participated in this study. Different groups of parents and their children took part in the two stages of this study. For Stage One, 202 parents participated in the parental involvement questionnaire from both private and public schools located in these two cities. 36 (18 parents for each experimental and control group) private school parents and their children participated in the Stage Two of this study. One private school from each city was selected to be the experimental and the control group. A quasi-experimental research design with experimental and control groups was used. Experimental and control groups were formed according to a matching technique which involve matching parents to the groups according to their involvement level, gender and education level. Parental involvement questionnaire, parents’ and children’s attitudes towards science questionnaire, weekly feedback forms, parents’ interviews were the main data collection tools for this study and these were used as pre and post-interventions. The intervention implemented with experimental group’s parents and their children for five weeks. Parents were provided with science activities of an online website and instructions through email and handout by the science teacher. They expected to practise these activities weekly with their child at home. The results from Stage One showed that parents’ level of involvement, role construction beliefs, self-efficacy beliefs and attitudes towards science were positive, but their perceptions of invitation from teachers and their child were low. The results from Stage Two demonstrated that the intervention positively increased parental involvement in their child’s general and science learning and the invitations from teachers and their child. A positively small difference for parents’ self-efficacy beliefs was also found. However, parents’ and children’s attitudes towards science and parents’ communication with teacher did not change after the intervention. In addition, a small decrease was found regarding parents’ role construction beliefs.

The academic achievement, of children and young people is an issue that concerns governments in many countries. In Nigeria, students’ performance on standardised examinations has been troublingly low, especially among those from the north of the country. Previous studies on students’ achievement have focused on inadequate funding, infrastructural decay, parental background factors and pedagogical issues. However, this study considers the psychological aspects of attainment, looking at the relationships between self-concept, locus of control, school motivation, academic achievement and other contextual factors (such as gender) that are likely to have an impact on students’ performance in school. The aim is to identify some of the factors contributing to low performance in order to generate empirical evidence to inform policy and practice. The study adopts a cross sectional research design with a sequential mixed method approach to data collection and analysis. Standardised questionnaires are used to measure key concepts in the first stage. The sample consists of Secondary School Students (SS1) from public schools in Kaduna State, Northern Nigeria. Semi-structured interviews are then used in the second stage to probe the factors influencing students’ performance. The results indicate high, moderate, and low levels of relationships between academic achievement and the conceptual variables, and that self-concept and mother’s profession are the main predictors of academic achievement. The study recommends that education practitioners and policy makers develop intervention programmes in order to enhance students’ adequate and positive perceptions of their academic abilities. These might include the use of tangible and non-tangible reward systems to reinforce academic and social accomplishments, the development of policies aimed at eradicating poverty so that families can make adequate provision for their children at home and at school. The government needs to improve school infrastructure to facilitate effective teaching and learning, and enhance the students’ personality attributes.

This thesis provides the first study of the representation, performance, and reception of Shakespeare’s ageing women in early modern and present-day England. It contributes an exposition of the physiology and theory of early modern ageing, drawing on this original material to make an argument for the ageing woman as a source of anxiety within the plays as they were originally staged, and as they are performed and received today. It finds the old and ageing woman in Shakespeare’s drama to be represented as physically and verbally excessive; the thesis also identifies a corresponding urge in the plays and in their reception towards the ageing woman’s containment and control. This containment is exercised in the text, the rehearsal room, the theatre, and the public space of performance reviews. My introduction determines my methodology and establishes the terms of reference for the project. The first chapter defines early modern old age and delivers a study of the early modern literature and theory of the ageing body. Each of the four subsequent chapters explores an ageing female character or characters through the lens of a theme: magic, motherhood, sexuality, and memory. The characters studied are drawn from The Merry Wives of Windsor, Macbeth, The Winter’s Tale, Coriolanus, King John, All’s Well That Ends Well, Antony and Cleopatra, Hamlet, and Richard III. Some brief concluding remarks complete the thesis. The larger project of the thesis is a cultural study. Throughout, I am keen to learn how characters are talked about as well as written and performed. My effort to understand the work which Shakespeare’s older women are asked to carry out in the present day defines my methodology: I draw on prompt books, production recordings, reviews, costume, photographs, programmes, and interviews with actors and directors to aid my investigation, juxtaposing these with close study of the written plays and the early modern culture and knowledge which underpins them. The word count, exclusive of bibliography but inclusive of all footnotes and an appendix, is approximately 92,000.

This is the first full-scale study of Robert Greene’s drama, offering a new interpretation of the dramatic oeuvre of one Shakespeare’s most neglected literary predecessors. Recent criticism has emphasised Greene’s pioneering role as an author of Elizabethan romance. Yet, in contrast to the numerous prose works which were printed during his life time, his drama, which was printed posthumously, has received little attention. Greene’s plays are visually magnificent: madmen wander on stage waving the severed limbs of their victims (Orlando Furioso, c. 1591), the dead are resurrected (James IV, c. 1590), tyrants gruesomely mutilate their subjects (Selimus, c. 1591-4), extravagant stage properties such as the mysterious brazen head prophesy to the audience (Friar Bacon and Friar Bungay, c. 1589), and sinners are swallowed into hell accompanied by fireworks (A Looking Glass for London and England, c. 1588). This thesis will examine the way in which these stage images evoke astonishment, which in turn encourages the audience to contemplate their symbolic significance. The triumph of Greene’s drama is not one of effects over affect; it lies in the interaction between effect and affect. My principal objective in this thesis is to develop a methodological strategy which will allow critics of non-Shakespearean plays, which frequently lack a substantial performance tradition, to study drama through the lens of performance. Engaging purposively with anachronism as an enabling mode of linking old and new, this thesis will draw analogies between the early modern stage and modern cinema in order to emphasise the relevance of early modern drama to today’s ocularcentric world, a relevance that more historical theoretical approaches would seek to deny. My opening chapter will try to establish Greene’s dramatic canon and assess the critical reception of Greene’s plays. Drawing on material from Greene’s entire oeuvre, Chapter Two will outline my methodological and conceptual approach. This chapter will include an extended analysis of Friar Bacon’s discussion of the ‘strategy with cunning shows’ in John of Bordeaux (JB. 735). Launching into detailed studies of specific spectacles, Chapter Three focuses on Thomas Lodge and Robert Greene’s collaborative effort, the biblical drama A Looking Glass for London and England. During the play, Prophet Jonah is ‘cast out of the whale’s belly upon the stage’ (LG. IV.i.1460-1). Focusing on this stage spectacle, this chapter seeks to emphasise the commercial appeal of this biblical drama. Examining another stage property, Chapter Four will explore the melodramatic and sensational potential of the tomb stage property in Greene’s James IV. Examining the apparent tension between the play’s two presenters, I will demonstrate that Bohan, a cynical Scot, and Oberon, the King of the Fairies, proffer two distinct, but not mutually exclusive, ways of conceiving of and interpreting theatrical spectacle. Completing my study of spectacular stage properties, Chapter Five examines the symbolic significance of the brazen head, which appears in two of Greene’s plays: Alphonsus, King of Aragon and Friar Bacon and Friar Bungay. In both plays, the brazen head becomes an object of excessive or supreme devotion as either a religious idol or a secular deity. The brazen head is perceived as monstrous not simply because it is a source of horror or astonishment but because it represents the misplaced veneration or worship of something other than God. Turning away from stage properties, my final two chapters look at how Greene exploited specific stage conventions. Directing my attention towards Greene’s Orlando Furioso (c. 1591), I will argue that the figure of Orlando Furioso bequeathed an enduring legacy to early modern theatrical discourse, contributing to the convention of the mad poet, which would be replicated and parodied by a new generation of dramatists. Orlando’s behaviour, which rapidly alternates between that of a madman and that of a poet, forces the audience to contemplate the link between the mania of the mentally ill and the melancholia of the creative genius. Ridiculing the concept of furor poeticus, Greene’s play interrogates the belief that great writers are divinely inspired by God through ecstatic revelation. My final chapter will explore the aesthetics of violence in Selimus. A relatively recent addition to the Greene canon, Selimus depicts the rise of an anti-hero amidst a cycle of brutal violence. My reading of this play posits Selimus as a surrogate playwright, arguing that the semiotics of dismemberment allows Greene to interrogate the concept of artistic autonomy. Widespread indifference to Greene’s work has facilitated critical blindness to the powerful aesthetic appeal of spectacle in early modern drama. This reassessment of Robert Greene’s dramatic oeuvre offers a new perspective on the aesthetics of spectacle in early modern drama.