Modelling the human accommodation system using finite element analysis

The human accommodation system has been extensively examined for over a century, with a particular focus on trying to understand the mechanisms that lead to the loss of accommodative ability with age (Presbyopia). The accommodative process, along with the potential causes of presbyopia, are disputed; hindering efforts to develop methods of restoring accommodation in the presbyopic eye. One method that can be used to provide insight into this complex area is Finite Element Analysis (FEA). The effectiveness of FEA in modelling the accommodative process has been illustrated by a number of accommodative FEA models developed to date. However, there have been limitations to these previous models; principally due to the variation in data on the geometry of the accommodative components, combined with sparse measurements of their material properties. Despite advances in available data, continued oversimplification has occurred in the modelling of the crystalline lens structure and the zonular fibres that surround the lens. A new accommodation model was proposed by the author that aims to eliminate these limitations. A novel representation of the zonular structure was developed, combined with updated lens and capsule modelling methods. The model has been designed to be adaptable so that a range of different age accommodation systems can be modelled, allowing the age related changes that occur to be simulated. The new modelling methods were validated by comparing the changes induced within the model to available in vivo data, leading to the definition of three different age models. These were used in an extended sensitivity study on age related changes, where individual parameters were altered to investigate their effect on the accommodative process. The material properties were found to have the largest impact on the decline in accommodative ability, in particular compared to changes in ciliary body movement or zonular structure. Novel data on the importance of the capsule stiffness and thickness was also established. The new model detailed within this thesis provides further insight into the accommodation mechanism, as well as a foundation for future, more detailed investigations into accommodation, presbyopia and accommodative restoration techniques.

Modeling Pulsatility in the Human Cardiovascular System

AMS Subj. Classification: 92C30

Contesting human rights through institutional reform:a case study of the reform of the UK Equality and Human Rights Commission

This article presents a case study of the recent reform of the United Kingdom Equalities and Human Rights Commission, to address a critical gap in the literature on national human rights institutions (NHRIs) concerning the power of governments to exert control over these institutions through reform processes. Through this analysis, the article demonstrates, first, that NHRIs are affected by contextual factors not only related to the popularity of the human rights agenda but also to wider policy agendas which impact on their status and functions; and second, that attempts by government to exert more administrative control can be significantly problematic for the operational independence of NHRIs.

Redefining 'media' using a 'media-as-a-constitutional-component' concept:an evaluation of the need for the European Court of Human Rights to alter its understanding of 'media' within a new media landscape

This paper considers the impact of new media on freedom of expression and media freedom within the context of the European Convention on Human Rights and European Court of Human Rights jurisprudence. Through comparative analysis of US jurisprudence and scholarship, this paper deals with the following three issues. First, it explores the traditional purpose of the media, and how media freedom, as opposed to freedom of expression, has been subject to privileged protection, within an ECHR context at least. Secondly, it considers the emergence of new media, and how it can be differentiated from the traditional media. Finally, it analyses the philosophical justifications for freedom of expression, and how they enable a workable definition of the media based upon the concept of the media-as-a-constitutional-component.

The United Nations Security Council Sanctions and International Human Rights

Peer reviewed

Italian-American Civil Rights League booth at the Fiesta of Maria S.S. della Grazie on Mulberry Street

General note: Title provided by Freda Leinwand.

Italian-American Civil Rights League sign at the Fiesta of Maria S.S. della Grazie on Mulberry Street

Inscriptions: Verso: [stamped] Photograph by Freda Leinwand. [463 West Street, Studio 229G, New York, NY 10014].

An investigation of the molecular interactions between statins and bacterial pathogens, and their combined impact on the human immune system

Statins are a class of drug that inhibits cholesterol biosynthesis, and are used to treat patients with high serum cholesterol levels. They exert this function by competitively binding to the enzyme 3-hydroxy-3-methylglutaryl-CoenzymeA reductase (HMGR), which catalyses the formation of mevalonate, a rate-limiting step in cholesterol biosynthesis. In addition, statins have what are called “pleiotropic effects”, which include the reduction of inflammation, immunomodulation, and antimicrobial effects. Statins can also improve survival of patients with sepsis and pneumonia. Cystic fibrosis (CF) is the most common recessive inherited disease in the Caucasian population, which is characterised by factors including, but not limited to, excessive lung inflammation and increased susceptibility to infection. Therefore, the overall objective of this study was to examine the effects of statins on CFassociated bacterial pathogens and the host response. In this work, the prevalence of HMGR was examined in respiratory pathogens, and several CF-associated pathogens were found to possess homologues of this enzyme. HMGR homology was analysed in Staphylococcus aureus, Burkholderia cenocepacia and Streptococcus pneumoniae, and the HMGR of B. cenocepacia was found to have significant conservation to that of Pseudomonas mevalonii, which is the most widely-characterised bacterial HMGR. However, in silico analysis revealed that, unlike S. aureus and S. pneumoniae, B. cenocepacia did not possess homologues of other mevalonate pathway proteins, and that the HMGR of B. cenocepacia appeared to be involved in an alternative metabolic pathway. The effect of simvastatin was subsequently tested on the growth and virulence of S. aureus, B. cenocepacia and S. pneumoniae. Simvastatin inhibited the growth of all 3 species in a dose-dependent manner. In addition, statin treatment also attenuated biofilm formation of all 3 species, and reduced in vitro motility of S. aureus. Interestingly, simvastatin also increased the potency of the aminoglycoside antibiotic gentamicin against B. cenocepacia. The impact of statins was subsequently tested on the predominant CF-associated pathogen Pseudomonas aeruginosa, which does not possess a HMGR homologue. Mevastatin, lovastatin and simvastatin did not influence the growth of this species. However, sub-inhibitory statin concentrations reduced the swarming motility and biofilm formation of P. aeruginosa. The influence of statins was also examined on Type 3 toxin secretion, quorum sensing and chemotaxis, and no statin effect was observed on any of these phenotypes. Statins did not appear to have a characteristic effect on the P. aeruginosa transcriptome. However, a mutant library screen revealed that the effect of statins on P. aeruginosa biofilm was mediated through the PvrR regulator and the Cup fimbrial biosynthesis genes. Furthermore, proteomic analysis demonstrated that 6 proteins were reproducibly induced by simvastatin in the P. aeruginosa swarming cells. The effect of statins on the regulation of the host-P. aeruginosa immune response was also investigated. Statin treatment increased expression of the pro-inflammatory cytokines IL-8 and CCL20 in lung epithelial cells, but did not attenuate P. aeruginosa-mediated inflammatory gene induction. In fact, simvastatin and P. aeruginosa caused a synergistic effect on CCL20 expression. The expression of the transcriptional regulators KLF2 and KLF6 was also increased by statins and P. aeruginosa, with the induction of KLF6 by simvastatin proving to be a novel effect. Interestingly, both statins and P. aeruginosa were capable of inducing alternative splicing of KLF6. P. aeruginosa was found to induce KLF6 alternative splicing by way of the type 3 secreted toxin ExoS. In addition, a mechanistic role was elucidated for KLF6 in the lung, as it was determined that statin-mediated induction of this protein was responsible for the induction of the host response genes CCL20 and iNOS. Moreover, statin treatment caused a slight increase in infection-related cytotoxicity, and increased bacterial adhesion to cells. Taken together, these data demonstrate that statins can reduce the virulence of CFassociated bacterial pathogens and alter host response effectors. Furthermore, novel statin effectors were identified in both bacterial and host cells.

Statelessness as a Human Rights Issue: A Concept Whose Time Has Come?

The protection of stateless persons has long been understood as a challenge for the international community, yet for many of the past sixty years a prioritised focus on refugees has dominated, indeed arguably eclipsed, the plight and protection needs of stateless persons. Guy Goodwin-Gill has long argued for a refocus of international attention and effort on the plight, predicament and protection needs of stateless persons. In a seminal contribution over two decades ago he observed that at that time, statelessness was perceived by many as a mere ‘technical problem,’ yet ‘statelessness is indeed a broad human rights issue, even as it retains a distinct technical dimension.’ In this contribution, we examine the challenge set by Goodwin-Gill for the international community, namely, the need for greater recognition and protection of stateless persons, in light of developments over the more than two decades that have passed since his incisive analysis. We celebrate the positive developments and identify areas of ongoing challenge. We focus on the key initiatives he identified as requiring attention, and assess progress that has been made in relation to each, while concentrating predominantly on the need for closer attention to the relevance of developments in human rights law.

Human Rights, Local Plights: The Implications of Rights Discourses in the Struggle over Arab-Palestinian Bedouin Land in Israel

A widely diffused, engaged approach understands human rights as an opportunity to enhance moral progress. Less visible has a critical realm of research that reveals the often ambiguous social life of human rights discourses. This article draws on a specific case study from the intricate issue of how activism for Arab-Palestinian Bedouin citizens in Southern Israel engages with the global human rights discourse. It follows the implications of mobilization, focusing on events related to a campaign against house demolitions in informal,unrecognised settlements. The case shows how human rights discourses tend to silence the agency of political subjects, victimizing and patronizing those who seek emancipation. The ethnographic insights emphasize the role of a range of carnivalesque and spontaneous acts ofresistance, which subvert the patronizing implications of the human rights language.