Feminist Post-structuralist discourse analysis: a new theoretical and methodological approach?

This chapter serves three very important functions within this collection. First, it aims to make the existence of FPDA better known to both gender and language researchers and to the wider community of discourse analysts, by outlining FPDA’s own theoretical and methodological approaches. This involves locating and positioning FPDA in relation, yet in contradistinction to, the fields of discourse analysis to which it is most often compared: Critical Discourse Analysis (CDA) and, to a lesser extent, Conversation Analysis (CA). Secondly, the chapter serves a vital symbolic function. It aims to contest the authority of the more established theoretical and methodological approaches represented in this collection, which currently dominate the field of discourse analysis. FPDA considers that an established field like gender and language study will only thrive and develop if it is receptive to new ways of thinking, divergent methods of study, and approaches that question and contest received wisdoms or established methods. Thirdly, the chapter aims to introduce some new, experimental and ground-breaking FPDA work, including that by Harold Castañeda-Peña and Laurel Kamada (same volume). I indicate the different ways in which a number of young scholars are imaginatively developing the possibilities of an FPDA approach to their specific gender and language projects.

Trigger release liposome systems:local and remote controlled delivery?

Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice

STUDY DESIGN: The twy/twy mouse undergoes spontaneous chronic mechanical compression of the spinal cord; this in vivo model system was used to examine the effects of retrograde adenovirus (adenoviral vector [AdV])-mediated brain-derived neurotrophic factor (BDNF) gene delivery to spinal neural cells. OBJECTIVE: To investigate the targeting and potential neuroprotective effect of retrograde AdV-mediated BDNF gene transfection in the chronically compressed spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes. SUMMARY OF BACKGROUND DATA: Several studies have investigated the neuroprotective effects of neurotrophins, including BDNF, in spinal cord injury. However, no report has described the effects of retrograde neurotrophic factor gene delivery in compressed spinal cords, including gene targeting and the potential to prevent neural cell apoptosis. METHODS: AdV-BDNF or AdV-LacZ (as a control gene) was injected into the bilateral sternomastoid muscles of 18-week old twy/twy mice for retrograde gene delivery via the spinal accessory motor neurons. Heterozygous Institute of Cancer Research mice (+/twy), which do not undergo spontaneous spinal compression, were used as a control for the effects of such compression on gene delivery. The localization and cell specificity of ß-galactosidase expression (produced by LacZ gene transfection) and BDNF expression in the spinal cord were examined by coimmunofluorescence staining for neural cell markers (NeuN, neurons; reactive immunology protein, oligodendrocytes; glial fibrillary acidic protein, astrocytes; OX-42, microglia) 4 weeks after gene injection. The possible neuroprotection afforded by retrograde AdV-BDNF gene delivery versus AdV-LacZ-transfected control mice was assessed by scoring the prevalence of apoptotic cells (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells) and immunoreactivity to active caspases -3, -8, and -9, p75, neurofilament 200 kD (NF), and for the oligodendroglial progenitor marker, NG2. RESULTS.: Four weeks after injection, the retrograde delivery of the LacZ marker gene was identified in cervical spinal neurons and some glial cells, including oligodendrocytes in the white matter of the spinal cord, in both the twy/twy mouse and the heterozygous Institute of Cancer Research mouse (+/twy). In the compressed spinal cord of twy/twy mouse, AdV-BDNF gene transfection resulted in a significant decrease in the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells present in the spinal cord and a downregulation in the caspase apoptotic pathway compared with AdV-LacZ (control) gene transfection. There was a marked and significant increase in the areas of the spinal cord of AdV-BDNF-injected mice that were NF- and NG2-immunopositive compared with AdV-LacZ-injected mice, indicating the increased presence of neurons and oligodendrocytes in response to BDNF transfection. CONCLUSION: Our results demonstrate that targeted retrograde BDNF gene delivery suppresses apoptosis in neurons and oligodendrocytes in the chronically compressed spinal cord of twy/twy mouse. Further work is required to establish whether this method of gene delivery may provide neuroprotective effects in other situations of compressive spinal cord injury.

Implementation of a machine tool performance measurement and diagnostic system and its impact on parts verification

Five axis machine tools are increasing and becoming more popular as customers demand more complex machined parts. In high value manufacturing, the importance of machine tools in producing high accuracy products is essential. High accuracy manufacturing requires producing parts in a repeatable manner and precision in compliance to the defined design specifications. The performance of the machine tools is often affected by geometrical errors due to a variety of causes including incorrect tool offsets, errors in the centres of rotation and thermal growth. As a consequence, it can be difficult to produce highly accurate parts consistently. It is, therefore, essential to ensure that machine tools are verified in terms of their geometric and positioning accuracy. When machine tools are verified in terms of their accuracy, the resulting numerical values of positional accuracy and process capability can be used to define design for verification rules and algorithms so that machined parts can be easily produced without scrap and little or no after process measurement. In this paper the benefits of machine tool verification are listed and a case study is used to demonstrate the implementation of robust machine tool performance measurement and diagnostics using a ballbar system.

Predictors of adolescent sexual intentions and behavior: Attitudes, parenting, and neighborhood risk

The current study was a cross-sectional examination of data collected during an HIV risk reduction intervention in south Florida. The purpose of the study was to explore the relationships between neighborhood stress, parenting, attitudes, and adolescent sexual intentions and behavior. The Theory of Planned Behavior was used as a model to guide variable selection and propose an interaction pathway between predictors and outcomes. Potential predictor variables measured for adolescents ages 13–18 (n=196) included communication about sex, parent-family connectedness, parental presence, parent-adolescent activity participation, attitudes about sex and condom use, neighborhood disorder, and exposure to violence. Outcomes were behavioral intentions and sexual behavior for the previous eight months. Neighborhood data was supplemented with ZIP Code level data from regional sources and included median household income, percentage of minority and Hispanic residents, and number of foreclosures. Statistical tests included t-tests, Pearson's correlations, and hierarchical linear regressions. Results showed that males and older adolescents reported less positive behavioral intentions than females and adolescents younger than 16. Intentions were associated with condom attitudes, sexual attitudes, and parental presence; unprotected sexual behavior was associated with parental presence. The best fit model for intentions included gender, sexual attitudes, condom attitudes, parental presence, and neighborhood disorder. The unsafe sexual behavior model included whether the participant lived with both natural parents in the previous year, and the percent of Hispanic residents in the neighborhood. Study findings indicate that more research on adolescent sexual behavior is warranted, specifically examining the differentials between variables that affect intentions and those that affect behavior. A focus on gender and age differences during intervention development may allow for better targeting and more efficacious interventions. Adding peer and media influences to the framework of attitudes, parenting, and neighborhood may offer more insight into patterns of adolescent sexual behavior risk.

Segmenting The Hotel Market

Marketing involves satisfying consumers' needs and wants with products of two types, goods and services. Hotels provide an intangible product, referred to as a service. On the other hand, toothpaste is an example of a product that is a tangible good. The lifeblood of both is marketing. Different as they are, each utilizes market segmentation and positioning. The segmentation movement in the hotel industry is analyzed in the light of marketing principles developed from the consumer goods sector. The analysis suggests that the hotel industry is engaged in a multiple segmentation strategy

The Influence of Psychological Predictors and Cognitive Behavioral Stress Management Intervention on Antiretroviral Therapy (ART) Adherence Among HIV-Positive Female Haitian Alcohol Users

Purpose: Over half the HIV-infected persons in the Caribbean, the second most HIV-impacted region in the world, live in Haiti. Using secondary data from a parent study, this research assessed the effects of psychological and social factors on antiretroviral therapy (ART) adherence among Haitian, HIV-positive, female alcohol users. Theoretical Foundation and Research Questions: Using the Theory of Planned Behavior/Reasoned Action and the Information, Motivation, Behavior skills model as guiding theoretical frameworks, the study examined the effectiveness of an adapted cognitive behavioral stress management (CBSM-A) intervention in improving ART adherence. The effect of psychological factors (depression, anxiety, beliefs about medicine, and social support), social factors (stigma, relationship status, and educational attainment), and alcohol on adherence to ART was assessed. Methods: The sample consisted of 116 female ART patients who were randomly assigned to the CBSM-A intervention or the wait-list control group. Participants completed intervention sessions as well as pre- and post-test assessments. Analyses of variance, t-tests, and point biserial correlations were used to test hypotheses. Results: Surprisingly, ART adherence rates significantly decreased for both groups combined [F (1, 108) = 8.79, p = .004]; there was no significant difference between the intervention and control groups with regard to the magnitude of change between baseline and post assessment. On average, depression decreased significantly among participants in the CBSM-A group only [(t (62) = 5.54, p < .001)]. For both groups combined, alcohol use significantly decreased between baseline and post-assessment [(F (1, 78) = 34.70, p < .001)]; there was no significant difference between the intervention and control groups with regard to the magnitude of change between baseline and post-assessment. None of the variables were significantly correlated with ART adherence. Discussion: Adherence to ART did not improve in this sample, nor were any of the variables significantly associated with adherence. The findings suggest that additional supportive and psychological services may be needed in order to promote higher adherence to ART among HIV-positive females. More research may be needed on this sample; a focus on mental health issues, partner conflict, family and sexual history may allow for better targeting and more successful interventions.

Qualidade dos serviços hoteleiros: percepções dos turistas de negócios de Teresina-PI

Business tourism is one of tourist segments with different market characteristics in relation to others segmentations, such as low seasonality, there is no requirement of natural attractions, it serves as destination projection and it generates profitable larger numbers. Due to the context around business travels, the hotel so many times has a fundamental whole among the elements of the production chain in this segmentation. Business tourism in Teresina is the primary segmentation of the capital, since it represents almost 70% of hotel demand; hence this research has as objective to evaluate through the perceptions of business travelers, the level of quality services of hotels of Teresina. The research is exploratory and descriptive, of functionalist character. This study is characterized by qualitative and quantitative research, supported by a basis of methodological pluralism. For primary data collection was performed applying a suitable research instrument of SERVPERF model (Service Performance). The universe of this study were Teresina's accommodations, restricted to only those that fit in hotel category and it was inside metropolitan area of Teresina. The study subjects were business travelers who were hosted in these hotels. For the analysis, it was considered certain factors: descriptive analysis, factor analysis, correlation matrix analysis of the variables; It was still compiling a graphic of lexicons obtained in the survey about respondent's the notion of quality of vision in the hotel service; Finally, qualitative analysis was based on the theories of marketing, targeting and quality of tourism services applied. The results show that the Teresina hotel service is on a regular average, especially for Reliability and Safety dimensions were highlighted. Whereas, the factor analysis showed the emergence of two factors to explain "Empathy" dimension, one of this is about the organization and the other one is about consumer. And by Lexicometria was possible to observe the importance to the customer of other variables such as: personal aspects, price and location for this tour segmentation.

Problematizing practice: MacIntyre and management

Alasdair MacIntyre’s distinction between institutions and practices helps illuminate how powerful institutional forces frame and constrain the practice of organizational research as well as the output and positioning of scholarly journals like Organization. Yet his conceptual frame is limited, not least because it is unclear whether the activity of managing is, or is not, a practice. This article builds on MacIntyre’s ideas by incorporating Aristotle’s concepts of poíēsis, praxis, téchnē and phrónēsis. Rather than ask, following MacIntyre, whether management is a practice, this wider network of concepts provides a richer frame for understanding the nature of managing and the appropriate role for academia. The article outlines a phronetic paradigm for organizational inquiry, and concludes by briefly examining the implications of such a paradigm for research and learning.

Design and Synthesis of Acridine-Based Macrocyclic G-Quadruplex DNA Ligands

DNA sequences that are rich in the guanine nucleic base possess the ability to fold into higher order structures called G-quadruplexes. These higher level structures are formed as a result of two sets of four guanine bases hydrogen-bonding together in a planar arrangement called a guanine quartet. Guanine quartets subsequently stack upon each other to form quadruplexes. G-quadruplexes are mainly localized in telomeres as well as in oncogene promoters. One unique and promising therapeutic approach against cancer involves targeting and stabilizing G-quadruplexes with small molecules, generally in order to suppress oncogene expression and telomerase enzyme activity; the latter has been found to contribute to “out-of control” cell growth in ca. 80-85% of all cancer cells and primary tumours while being absent in normal somatic cells. In this work, we present efforts towards designing and synthesizing acridine-based macrocycles (Mh) and (Mb) with the purpose of providing potential G4 ligands that are suited for selective binding to G4 vs. duplex DNA, and stabilize G-quadruplex structures. Two ligands described in this study include an acridine core which provides an aromatic surface capable of π-π interactions with the surface of G-quadruplexes. The successful synthesis of 4,5-diaminoacridine is described in chapter 2, as an essential fragment of the macrocycles (Mh) and (Mb). In order to investigate the synthetic method for macrocyclization, model compounds composing almost half of the designed macrocycles were explored. As discussed in chapter 3, the synthesis of the model compound for (Mb) turned out to be challenging. However, as a step towards the synthesis of (Mh), the synthesis of the hydrogen-containing model compound, which is almost half of the desired macrocycle (Mh) was achieved in our group and proved to be promising.

Looking Beyond ‘White Slavery’: Trafficking, the Jewish Association’s representation of ‘the potential victim’, and the dangerous politics of migration control in England, 1890-1910

This article seeks to revise Jo Doezema’s suggestion that ‘the white slave’ was the only dominant representation of ‘the trafficked woman’ used by early anti-trafficking advocates in Europe and the United States, and that discourses based on this figure of injured innocence are the only historical discourses that are able to shine light on contemporary anti-trafficking rhetoric. ‘The trafficked woman’ was a figure painted using many shades of grey in the past, with a number of injurious consequences, not only for trafficked persons but also for female labour migrants and migrant populations at large. In England, dominant organizational portrayals of ‘the trafficked woman’ had first acquired these shades by the 1890s, when trafficking started to proliferate amid mass migration from Continental Europe, and when controversy began to mount over the migration to the country of various groups of working-class foreigner. The article demonstrates these points by exploring the way in which the Jewish Association for the Protection of Girls and Women (JAPGW), one of the pillars of England’s early anti-trafficking movement, represented the female Jewish migrants it deemed at risk from being trafficked into sex work between 1890 and 1910. It argues that the JAPGW stigmatised these women, placing most of the onus for trafficking upon them and positioning them to a greater or a lesser extent as ‘undesirable and undeserving working-class foreigners’ who could never become respectable English women. It also contends that the JAPGW, in outlining what was wrong with certain female migrants, drew a line between ‘the migrant’ and respectable English society at large, and paradoxically endorsed the extension of the very ‘anti-alienist’ and Antisemitic prejudices that it strove to dispel.

Essays on optimal fiscal and monetary policies

Cette thèse se compose de trois articles sur les politiques budgétaires et monétaires optimales. Dans le premier article, J'étudie la détermination conjointe de la politique budgétaire et monétaire optimale dans un cadre néo-keynésien avec les marchés du travail frictionnels, de la monnaie et avec distortion des taux d'imposition du revenu du travail. Dans le premier article, je trouve que lorsque le pouvoir de négociation des travailleurs est faible, la politique Ramsey-optimale appelle à un taux optimal d'inflation annuel significativement plus élevé, au-delà de 9.5%, qui est aussi très volatile, au-delà de 7.4%. Le gouvernement Ramsey utilise l'inflation pour induire des fluctuations efficaces dans les marchés du travail, malgré le fait que l'évolution des prix est coûteuse et malgré la présence de la fiscalité du travail variant dans le temps. Les résultats quantitatifs montrent clairement que le planificateur s'appuie plus fortement sur l'inflation, pas sur l'impôts, pour lisser les distorsions dans l'économie au cours du cycle économique. En effet, il ya un compromis tout à fait clair entre le taux optimal de l'inflation et sa volatilité et le taux d'impôt sur le revenu optimal et sa variabilité. Le plus faible est le degré de rigidité des prix, le plus élevé sont le taux d'inflation optimal et la volatilité de l'inflation et le plus faible sont le taux d'impôt optimal sur le revenu et la volatilité de l'impôt sur le revenu. Pour dix fois plus petit degré de rigidité des prix, le taux d'inflation optimal et sa volatilité augmentent remarquablement, plus de 58% et 10%, respectivement, et le taux d'impôt optimal sur le revenu et sa volatilité déclinent de façon spectaculaire. Ces résultats sont d'une grande importance étant donné que dans les modèles frictionnels du marché du travail sans politique budgétaire et monnaie, ou dans les Nouveaux cadres keynésien même avec un riche éventail de rigidités réelles et nominales et un minuscule degré de rigidité des prix, la stabilité des prix semble être l'objectif central de la politique monétaire optimale. En l'absence de politique budgétaire et la demande de monnaie, le taux d'inflation optimal tombe très proche de zéro, avec une volatilité environ 97 pour cent moins, compatible avec la littérature. Dans le deuxième article, je montre comment les résultats quantitatifs impliquent que le pouvoir de négociation des travailleurs et les coûts de l'aide sociale de règles monétaires sont liées négativement. Autrement dit, le plus faible est le pouvoir de négociation des travailleurs, le plus grand sont les coûts sociaux des règles de politique monétaire. Toutefois, dans un contraste saisissant par rapport à la littérature, les règles qui régissent à la production et à l'étroitesse du marché du travail entraînent des coûts de bien-être considérablement plus faible que la règle de ciblage de l'inflation. C'est en particulier le cas pour la règle qui répond à l'étroitesse du marché du travail. Les coûts de l'aide sociale aussi baisse remarquablement en augmentant la taille du coefficient de production dans les règles monétaires. Mes résultats indiquent qu'en augmentant le pouvoir de négociation du travailleur au niveau Hosios ou plus, les coûts de l'aide sociale des trois règles monétaires diminuent significativement et la réponse à la production ou à la étroitesse du marché du travail n'entraîne plus une baisse des coûts de bien-être moindre que la règle de ciblage de l'inflation, qui est en ligne avec la littérature existante. Dans le troisième article, je montre d'abord que la règle Friedman dans un modèle monétaire avec une contrainte de type cash-in-advance pour les entreprises n’est pas optimale lorsque le gouvernement pour financer ses dépenses a accès à des taxes à distorsion sur la consommation. Je soutiens donc que, la règle Friedman en présence de ces taxes à distorsion est optimale si nous supposons un modèle avec travaie raw-efficace où seule le travaie raw est soumis à la contrainte de type cash-in-advance et la fonction d'utilité est homothétique dans deux types de main-d'oeuvre et séparable dans la consommation. Lorsque la fonction de production présente des rendements constants à l'échelle, contrairement au modèle des produits de trésorerie de crédit que les prix de ces deux produits sont les mêmes, la règle Friedman est optimal même lorsque les taux de salaire sont différents. Si la fonction de production des rendements d'échelle croissant ou decroissant, pour avoir l'optimalité de la règle Friedman, les taux de salaire doivent être égales.

Perpetual private land conservation: the case for outdoor recreation and functional leisure

As natural areas, agricultural lands, and open spaces continue to be developed at unprecedented rates, it is important for land conservation professionals to understand the individuals who might play a role in permanently protecting these lands and their ecological services. Many factors have been shown to influence land protection decisions among private owners, including land-use activities, demographic characteristics, and environmental intention and behavior. With the hypothesis that individuals already involved in land conservation programs would be candidates for permanent protection, we set out to model conservation easement decisions within a group of participants in southern Indiana’s Classified Forest and Wildlands Program (ICFWP). We used a mailed questionnaire to survey 500 landowners, garnering 308 responses, about their interest in conservation easements. Our results indicated significant positive relationships between interest in conservation easements with variables representing perception of landscape change, outdoor recreation behavior as an adult, and environmental organization membership. By better understanding the ways these factors promote permanent land-use decisions, land conservation professionals can better allocate limited resources through strategic investments in targeting and outreach.

Soft tissue sarcoma: biology and therapeutic correlates

Soft tissue sarcomas (STS) comprise a heterogenenous group of greater than 50 malignancies of putative mesenchymal cell origin and as such they may arise in diverse tissue types in various anatomical locations throughout the whole body. Collectively they account for approximately 1% of all human malignancies yet have a spectrum of aggressive behaviours amongst their subtypes. They thus pose a particular challenge to manage and remain an under investigated group of cancers with no generally applicable new therapies in the past 40 years and an overall 5-year survival rate that remains stagnant at around 50%. From September 2000 to July 2006 I undertook a full time post-doctoral level research fellowship at the MD Anderson Cancer Center, Houston, Texas, USA in the department of Surgical Oncology to investigate the biology of soft tissue sarcoma and test novel anti- sarcoma adenovirus-based therapy in the preclinical nude rat model of isolated limb perfusion against human sarcoma xenografts. This work, in collaboration with colleagues as indicated herein, led to a number of publications in the scientific literature furthering our understanding of the malignant phenotype of sarcoma and reported preclinical studies with wild-type p53, in a replication deficient adenovirus vector, and oncolytic adenoviruses administered by isolated limb perfusion. Additional collaborative and pioneering preclinical studies reported the molecular imaging of sarcoma response to systemically delivered therapeutic phage RGD-4c AAVP. Doxorubicin chemotherapy is the single most active broadly applicable anti-sarcoma chemotherapeutic yet only has an approximate 30% overall response rate with additional breakthrough tumour progression and recurrence after initial chemo-responsiveness further problematic features in STS management. Doxorubicin is a substrate for the multi- drug resistance (mdr) gene product p-glycoprotein drug efflux pump and exerts its main mode of action by induction of DNA double-strand breaks during the S-phase of the cell cycle. Two papers in my thesis characterise different aspects of chemoresistance in sarcoma. The first shows that wild-type p53 suppresses Protein Kinase Calpha (PKCα) phosphorylation (and activation) of p-glycoprotein by transcriptional repression of PKCα through a Sp-1 transcription factor binding site in its -244/-234 promoter region. The second paper demonstrates that Rad51 (a central mediator of homologous recombination repair of double strand breaks) has elevated levels in sarcoma and particularly in the S- G2 phase of the cell cycle. Suppression of Rad51 with small interfering RNA in sarcoma cell culture led to doxorubicin chemosensitisation. Reintroduction of wild-type p53 into STS cell lines resulted in decreased Rad51 protein and mRNA expression via transcriptional repression of the Rad51 promoter through increased AP-2 binding. In light of poor response rates to chemotherapy, escape from local control portends a poor prognosis for patients with sarcoma. Two papers in my thesis characterise aspects of sarcoma angiogenesis, invasion and metastasis. Human sarcoma samples were found to have high levels of matrix metalloproteinase-9 (MMP-9) with expression levels that correlated with p53 mutational status. MMP-9 is known to degrade extracellular collagen, contribute to the control of the angiogenic switch necessary in primary tumour progression and facilitate invasion and metastasis. Reconstitution of wild-type p53 function led to decreased levels of MMP-9 protein and mRNA as well as zymography-assessed MMP-9 proteolytic activity and decreased tumour cell invasiveness. Reintroduction of wild-type p53 into human sarcoma xenografts in-vivo decreased tumour growth and MMP-9 protein expression. Wild-type p53 was found to suppress mmp-9 transcription via decreased binding of NF-κB to its -607/-595 mmp-9 promoter element. Studies on the role of the VEGF165 in sarcoma found that sarcoma cells stably transfected with VEGF165 formed more aggressive xenografted tumours with increased vascularity, growth rate, metastasis, and resistance to chemotherapy. Use of the anti-VEGFR2 antibody DC101 enhanced doxorubicin sensitivity at sub-conventional dosing, inhibited tumour growth, decreased development of metastases, and reduced tumour micro-vessel density while increasing the vessel maturation index. These effects were explained primarily through effects on endothelial cells (e.c.s), rather than the tumour cells per se, where DC101 induced e.c. sensitivity to doxorubicin and suppressed e.c. production of MMPs. The p53 tumour suppressor pathway is the most frequently mutated pathway in sarcoma. Recapitulation of wild-type p53 function in sarcoma exerts a number of anti-cancer outcomes such as growth arrest, resensitisation to chemotherapy, suppression of invasion, and attenuation of angiogenesis. Using a modified nude rat-human sarcoma xenograft model for isolated limb perfusion (ILP) delivery of wild-type p53 in a replication deficient adenovirus vector I showed that functionally competent wild-type p53 could be delivered to and detected in human leiomyosarcoma xenografts confirming preclinical feasibility - although not efficacious due to low transgene expression. Viral fibre modification to express the RGD tripeptide motif led to greater viral uptake by sarcoma cells in vitro (transductional targeting) and changing the transgene promoter to a response element active in cells with active telomerase expression restricted the transgene expression to the tumour intracellular environment (transcriptional targeting). Delivery of the fibre-modified, selectively replication proficient oncolytic adenovirus Ad.hTC.GFP/ E1a.RGD by ILP demonstrated a more robust, and tumour-restricted, transgene expression with evidence of anti-sarcoma effect confirmed microscopically. Collaborative studies using the fibre modified phage RGD-4C AAVP confirmed that systemic delivery specifically, efficiently, and repeatedly targets human sarcoma xenografts, binds to αv integrins in tumours, and demonstrates a durable, though heterogeneous, transgene expression of 1-4 weeks. Incorporation of the Herpes Simplex Virus thymidine kinase (HSVtk) transgene into RGD-4C AAVP permitted CT-PET spatial and temporal molecular imaging in vivo of transgene expression and allowed quantification of tumour metabolic activity both before and after interval administration of a systemic cytotoxic with predictable and measurable response to treatment before becoming apparent clinically. These papers further the medical and scientific community’s understanding of the biology of soft tissue sarcoma and report preclinical studies with novel and promising anti- sarcoma therapeutics.

Towards a Bourdieusian analysis of the disabled body and practice: embodying negative symbolic capitals and the uneasy experience of hysteresis

Within the last few years, disabled people have become the target of government austerity measures through drastic cuts to welfare justified through the portrayal of benefit claimants as inactive, problem citizens who are wilfully unemployed. For all that is wrong with these cuts, they are one of many aspects of exclusion that disabled people face. Attitudes towards disability are deteriorating (Scope, 2011) and disabled people are devalued and negatively positioned in a myriad of ways, meaning that an understanding of the perceptions and positioning of disability and the power of disabling practices is critical. This thesis will examine how Bourdieu’s theoretical repertoire may be applied to the area of Disability Studies in order to discern how society produces oppressive and exclusionary systems of classification which structures the social position and perceptions of disability. The composite nature of disability and multiple forms of exclusion and inequality associated with it benefits from a multipronged approach which acknowledges personal, embodied and psychological aspects of disability alongside socio-political and cultural conceptualisations. Bourdieu’s approach is one in which the micro and macro aspects of social life are brought together through their meso interplay and provides a thorough analysis of the many aspects of disability.