In Vivo Fluorescence Imaging of E-Selectin: Quantitative Detection of Endothelial Activation in Arthritis

Rheumatoid arthritis (RA) is a chronic progressive systemic inflammatory disease, characterized by synovial inflammation and localized destruction of cartilage and bone. Heterogeneity in the clinical presentation of RA and uncertainty about which patients will respond to treatment makes diagnosis and management challenging. Fluorescent imaging in the near infrared (NIR) spectrum significantly decreases tissue autofluorescence offering unique potential to detect specific molecular targets in vivo. E-selectin or endothelial adhesion molecule-1 (ELAM-1), a 115kDa glycoprotein induced on endothelial cells in response to pro-inflammatory cytokines involved in RA, such as interleukin (IL)-1 beta and tumour necrosis factor alpha (TNF alpha). E-selectin has been well validated as a potential biomarker of disease activity. My study aimed to investigate whether E-selectin targeted optical imaging in vivo could be developed as a sensitive, specific and quantifiable preclinical molecular imaging technique, and also whether this approach could be used to delineate the molecular effects of novel therapies. I utilised anti-E-selectin antibody labelled with NIR fluorophore in a mouse model of paw swelling induced by intra-plantar injection of TNF alpha, and in acute collagen-induced arthritis (CIA) in DBA/1 mice, a widely used model of RA. E-selectin generated signal, localised to points of maximal clinical inflammation in the inflamed mouse paw in both models with significant differences to control antibody. Binding of anti-E-selectin antibody was also demonstrated by immunohistochemistry in both models. The ability of E-selectin targeted imaging to detect sub-clinical endothelial activation was also investigated, demonstrating that E-selectin may be an excellent way of determining subclinical vascular activation in CIA. Finally the effect of novel targeted therapy – RB200 which blocks epidermal growth factor (EGF) signalling was investigated. This demonstrated that E-selectin targeted signal could be absolutely abrogated to a level seen in unimmunised healthy control animals, following combination treatment with RB200 and the TNF alpha inhibitor etanercept. E-selectin targeted optical imaging is a viable in vivo imaging technique that can also be applied to quantify disease and investigate the effects of novel molecular therapies. It holds significant promise as a molecular imaging technique for future translation into the clinic for patients with rheumatoid arthritis and other inflammatory diseases

Knowledge, education and social differentiation amongst the Betsileo of Fisakana, highland Madagascar

This thesis is an ethnographic study of a village in Fisakana, an area of highland Madagascar where the institution of formal education has had great social, economic and cultural influence. Although the principal means of subsistence in Fisakana is wet rice cultivation, a severe shortage of good land has led to large-scale emigration. Schooling has provided opportunities for social and spatial mobility that have shaped the character of the region. Migration and movement are dominant themes in the ethnography of Madagascar. The thesis examines three different types of migration in Fisakana. Each entails a different type of relationship between the migrants and their ancestral land. These are discussed in the context of other literature dealing with this topic in the anthropology of Madagascar. The region is characterised by inequalities of wealth. People working in the profession sector have prospered economically in comparison to those dependent on agriculture. This thesis makes an original contribution to the literature on social and economic differentiation in the highlands by treating the subject from an ethnographic perspective. The role of formal education in widening socio-economic differentiation is explored in detail. Then the thesis studies how this differentiation is elaborated symbolically through the building of houses and tombs. it also points out the ambiguous nature of tomb ceremonies: whilst ostensibly symbolising social unity and cohesion, they also imply fissure and exclusion. The thesis then examine the Betsileo social construction of knowledge. Through an exploration of what is learned inside and outside the classroom the thesis shows how local notions of traditional and foreign knowledge articulate with missionary, colonial and post-colonial ideologies of schooling, and with the social and spatial differentiation and displacement produced by formal education

Education y Justicia: A Living History of the Latinx Experience in U.T Austin

Social policy in the United States has historically and systematically prevented Latinx students from attaining educational equity. The resistance to this inequality in Austin is located in institutional spaces, the creation of cultural spaces, and the reclamation of erased histories. This has lead to the need for the creation of cultural spaces and legislation that encourage the equity, power, and culture of the Latinx community. We are mapping these living histories of resistance to help form frameworks for rethinking educational social policy. In this case we used U.T. and the greater Austin area to explore the living histories of the struggle for educational justice in our city and propose frameworks for rethinking educational social policy.Mexican American Studie

The Evolution of American Microtargeting: An Examination of Trends in Political Messaging

The usage of targeted messaging by political campaigns has seen a drastic evolution over the past half-century. Through advancement in campaign technology, and an increasingly large amount of personal information up for sale, campaigns have continually narrowed their scope from targeting large demographic groups to targeting each voter individually through a process called microtargeting. This presentation examines both the history of microtargeting in American politics, and the potential effects of its utilization

Is There High-Level Causation?

The discovery of high-level causal relations seems a central activity of the special sciences. Those same sciences are less successful in formulating strict laws. If causation must be underwritten by strict laws, we are faced with a puzzle (first noticed by Donald Davidson), which might be dubbed the 'no strict laws' problem for high-level causation. Attempts have been made to dissolve this problem by showing that leading theories of causation do not in fact require that causation be underwritten by strict laws. But this conclusion has been too hastily drawn. Philosophers have tended to equate non-strict laws with ceteris paribus laws. I argue that there is another category of non-strict law that has often not been properly distinguished: namely, (what I will call) minutiae rectus laws. If, as it appears, many special science laws are minutiae rectus laws, then this poses a problem for their ability to underwrite causal relations in a way that their typically ceteris paribus nature does not. I argue that the best prospect for resolving the resurgent 'no strict laws' problem is to argue that special science laws are in fact typically probabilistic (and thus able to support probabilistic causation), rather than being minutiae rectus laws