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

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

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

The sustainable society

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Why anti-outsourcing is back at Sussex University

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Alternative societies

A distinctive characteristic of sociology is that it’s a critical discipline. But a question that criticisms of society imply is - what’s the alternative? This lecture will look at alternative societies implied by criticisms of existing ones. What is the role of utopianism? After the collapse of socialism in the late 20th century and the spread of capitalism and liberalism, is communism an alternative? Can we envisage a world with much less work, or no borders in the way of free movement? What alternative types of living are possible, economically, socially, educationally, politically, ecologically and that overcome divisions of class, gender and race

Set Reconstruction on the Hypercube

Given an action of a group $G$ on a set $S$, the $k$-deck of a subset $T$ of $S$ is the multiset of all subsets of $T$ of size $k$, each given up to translation by $G$. For a given subset $T$, the {\em reconstruction number} of $T$ is the minimum $k$ such that the $k$-deck uniquely identifies $T$ up to translation by $G$, and the {\em reconstruction number} of the action $G:S$ is the maximum reconstruction number of any subset of $S$. The concept of reconstruction number extends naturally to multisubsets $T$ of $S$ and in~\cite{CPC:257539}, the author calculated the multiset-reconstruction number of all finite abelian groups. In particular, it was shown that the multiset-reconstruction number of $\mathbb{Z}_2^n$ was $n+1$. This provides an upper bound of $n+1$ to the reconstruction number of $\mathbb{Z}_2^n$. The author also showed a lower bound of $\lfloor{\frac{n+1}2}\rfloor$ in the same paper. The purpose of this note is to close the gap. The reconstruction number of $\mathbb{Z}_2^n$ is $\lfloor{n+1-\log_2(n+1-\log_2(n))}\rfloor.$Comment: 10 page

Why the UK should have open borders

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