Brucellosis in northern Tanzania: Investigating the epidemiology of human infection and evaluating diagnostic test performance in animal hosts

Brucellosis is a widespread neglected zoonotic disease. It can cause severe and prolonged illness in people, as well as impacting on animal health and productivity. Brucellosis is endemic in much of sub-Saharan Africa (SSA). The global burden of brucellosis is suspected to be highest in SSA, where there are many livestock-keeping communities. Cattle, sheep and goats are common maintenance hosts of zoonotic Brucella spp. Pastoralist communities in frequent contact with these livestock species are at increased risk of infection. This study was performed to improve our understanding of the epidemiology of brucellosis in Tanzania through: a risk factor analysis for human acute brucellosis cases; trialling an active surveillance approach to identify additional cases through household screening in a high-risk population; and latent class analyses to evaluate diagnostic test performance in different animal hosts. In Chapter 2, questionnaire data were collected from febrile patients attending a rural hospital in the Ngorongoro Conservation Area (NCA), Tanzania. Risk factors associated with acute brucellosis were: having herded cattle, sheep and/or goats in the past 12 months; and decreasing age in years. In Chapter 3, active surveillance in the form of screening household members of febrile patients for exposure to Brucella spp. was implemented in the NCA. Screening household members of febrile patients with acute brucellosis led to identification of additional acute cases. However, the study did not find a significant association between the Brucella spp. exposure of household members and the household member who sought care at hospital. In Chapter 4, Bayesian latent class analyses were used to evaluate the Rose Bengal plate test (RBT) and the competitive enzyme-linked immunosorbent assay (cELISA) for the diagnosis of livestock brucellosis in northern Tanzania. Sensitivity was variable across livestock models, RBT sensitivity was comparable to cELISA in the bovine model and greater than cELISA in ovine and caprine models. RBT and cELISA specificity was essentially comparable in all livestock models. Conducting parallel RBT and cELISA testing optimised diagnostic test performance in all livestock models. These novel findings can inform the development and implementation of effective, evidence-based brucellosis prevention and control measures in SSA. Improved knowledge of acute human brucellosis risk factors is important in understanding temporally relevant risks associated with active infection and is a vital tool in developing interventions that prevent transmission. Active surveillance by screening household members requires further study but may prove too resource-intensive for routine implementation in Tanzania. However, it can provide valuable data on disease burden for the population that do not reach a healthcare facility, as well as assist in targeting prevention and control measures towards high-risk populations. In livestock, a parallel RBT and cELISA diagnostic testing approach, potentially implemented at the herd/flock level, would be more effective than using either test alone or serial approaches. Using these data, identification of a national sampling and testing approach can guide the development of a surveillance strategy which is a crucial step towards improving our understanding of brucellosis burden across livestock-keeping settings in Tanzania and wider SSA

Ceramics and locational identity: investigating the symbolism of material culture in relation to a sense of place

This article is an investigation into material culture and its symbolism regarding place and space and addresses the research question ‘why do select ceramic artefacts evoke or become symbolic of a specific location and sense of place?’ The research covers the areas of conceptual ceramic design, craft, culture and practice-led research. Dutch design duo Nadine Sterk and Lonny van Ryswyck – Atelier NL are discussed as an example of contemporary designer makers who create objects that embody social meaning and express an evocative sense of locational identity. The two Eindhoven-based designer-makers’ creative process combines and reveals different strands of academic and material enquiry and representing a creative process that flows between making, scientific knowledge, anthropology, archaeology, geology, art, design and craft. Atelier NL’s practice is representative of a current interest within visual and material culture in both practice-led research and socially engaged practice. The narrative of their research-based practice is unequivocally part of the production and presentation of their work. Atelier NL’s practice stands for a creative partnership that investigates and celebrates their locality as well as responding to a sense of ‘culture loss’ indicative of mainstream patterns of design, production and consumption of goods and services

The mind-body relationship and French poetry (c 1240-1500)

Accounts of French medieval verse have always supposed that there was no readily identifiable general theory of poetry in the Middle Ages. At most, it is accepted that there were arts of versification (the Latin Poetrie of the XII/XIII centuries, the French Arts de Seconde Rhetorique of the XVth century), which covered points of grammar, rather than of "theory" as the term is usually understood. However, there were non-literary theories which were systematically used by certain medieval poets. They derived from Greco-Arabic, rather than Latin, learning. The most unstable of these were theories concerning the relationship of mind and body - in sleep, in semi-wakefulness and in melancholy. Encyclopedists and men of learning began to relate poetry to the sciences of the quadrivium in Late Antiquity (Augustine, Boethius). This tendency became increasingly clear in the XII/XIII centuries, at the same time as the diffusion of texts like the Avicenna Canon of Medicine and the pseudo-Aristotelian Problemata. Jean de Meun was the first French author to relate the new sciences to poetic expression on an important scale. His discoveries were exploited by a number of poets in the XIV/XV centuries. The first major poets to use an art of poetry (that is, an ars poetica, rather than an ars versificatoria) and to apply its lessons to their work were Chastelain and Francois Villon. Their use of Averroes's commentary on Aristotle - the Poetria Aristotelis - has gone unnoticed. Towards the end of the fifteenth century French poetry evolved away from its interest in science in the direction of a number of ill-defined aims. Some of these were moralizing, others appear to be concerned with pure technique. Almost none of the poetry then written attempted to imitate the qualities of classical verse. It was concerned with problems of formal expression, rather than with exploring the structure of the mind or of the universe, as previously

The interaction of transforming growth factor beta and pro-inflammatory signalling in peritoneal fibrosis

Thesis Summary Peritoneal fibrosis is a significant problem for peritoneal dialysis patients resulting in a loss in membrane dialysing capacity ultimately leading to technique failure. The development of peritoneal fibrosis is attributed to recurrent peritonitis infections and bio-incompatible dialysate fluid, both of which contribute to a chronic inflammatory state within the peritoneum. Transforming growth factor beta 1 (TGF-(31) is a cytokine with a central role in peritoneal fibrosis. However, this cytokine has multiple key roles, including development, wound healing cell proliferation and differentiation and regulation of the immune response. Cellular response to TGF- 131 can vary depending on cellular context and phenotype. Factors governing responses to TGF-131 within the peritoneum are poorly characterised. Previous research through a murine model representing inflammation driven fibrosis has identified Interferon gamma (IFN-y) having a central role in inflammation driven fibrosis. Therefore examination of the interaction between TGF-(31 and IFN-y were undertaken in both murine samples and primary human peritoneal cells (HPMC). Within the SES murine model differences in TGF-131 responses were observed between WT and IL6KO mice, with WT mice displaying significant increase in expression of TGF-131 and matrix genes. There was increased expression of matrix metalloproteinases 3 and 10 (MMP3 and MMP10) in 116K0 mice, suggesting that these mice are protected against scarring and fibrosis through enhanced tissue remodelling. Similar findings were observed in HPMC treated with TGF-131 alone resulting in significant increased MMP3 expression, which was inhibited in the presence of IFN-y. IFN-y did not affect any other TGF-131 induced responses thus suggesting a specific fibrotic effect of IFN-y within this system by inhibiting matrix degradation. Analysis of the mechanism of MMP3 regulation by TGF-131 and IFN-y revealed that SMAD and MAPK pathways are involved in the induction of MMP3 by TGF-131 and are not inhibited by IFN-y. Analysis of the AP-1 promoter site in the MMP3 revealed that this site may be involved in basal MMP3 expression but is not modulated by TGF-I31 and IFN-y. Further examination of MMP3 regulation may provide a potential target in helping protect against peritoneal fibrosis, thus helping reduce technique failure in peritoneal dialysis

euMMD: efficiently computing the MMD two-sample test statistic for univariate data

The maximum mean discrepancy (MMD) test is a nonparametric kernelised two-sample test that, when using a characteristic kernel, can detect any distributional change between two samples. However, when the total number of d -dimensional observations is n , direct computation of the test statistic is O(dn2) . While approximations with lower computational complexity are known, more efficient methods for computing the exact test statistic are unknown. This paper provides an exact method for computing the MMD test statistic for the univariate case in O(nlogn) using the Laplacian kernel. Furthermore, this exact method is extended to an approximate method for d -dimensional real-valued data also with complexity log-linear in the number of observations. Experiments show that this approximate method can have good statistical performance when compared to the exact test, particularly in cases where d>n