Prevalence and associations of Trypanosoma spp. and Sodalis glossinidius with intrinsic factors of tsetse flies

Trypanosomiasis has been identified as a neglected tropical disease in both humans and animals in many regions of sub-Saharan Africa. Whilst assessments of the biology of trypanosomes, vectors, vertebrate hosts and the environment have provided useful information about life cycles, transmission, and pathogenesis of the parasites that could be used for treatment and control, less information is available about the effects of interactions among multiple intrinsic factors on trypanosome presence in tsetse flies from different sites. It is known that multiple species of tsetse flies can transmit trypanosomes but differences in their vector competence has normally been studied in relation to individual factors in isolation, such as: intrinsic factors of the flies (e.g. age, sex); habitat characteristics; presence of endosymbionts (e.g. Wigglesworthia glossinidia, Sodalis glossinidius); feeding pattern; host communities that the flies feed on; and which species of trypanosomes are transmitted. The purpose of this study was to take a more integrated approach to investigate trypanosome prevalence in tsetse flies. In chapter 2, techniques were optimised for using the Polymerase Chain Reaction (PCR) to identify species of trypanosomes (Trypanosoma vivax, T. congolense, T. brucei, T. simiae, and T. godfreyi) present in four species of tsetse flies (Glossina austeni, G. brevipalpis, G. longipennis and G. pallidipes) from two regions of eastern Kenya (the Shimba Hills and Nguruman). Based on universal primers targeting the internal transcribed spacer 1 region (ITS-1), T. vivax was the predominant pathogenic species detected in flies, both singly and in combination with other species of trypanosomes. Using Generalised Linear Models (GLMs) and likelihood ratio tests to choose the best-fitting models, presence of T. vivax was significantly associated with an interaction between subpopulation (a combination between collection sites and species of Glossina) and sex of the flies (X2 = 7.52, df = 21, P-value = 0.0061); prevalence in females overall was higher than in males but this was not consistent across subpopulations. Similarly, T. congolense was significantly associated only with subpopulation (X2 = 18.77, df = 1, P-value = 0.0046); prevalence was higher overall in the Shimba Hills than in Nguruman but this pattern varied by species of tsetse fly. When associations were analysed in individual species of tsetse flies, there were no consistent associations between trypanosome prevalence and any single factor (site, sex, age) and different combinations of interactions were found to be significant for each. The results thus demonstrated complex interactions between vectors and trypanosome prevalence related to both the distribution and intrinsic factors of tsetse flies. The potential influence of the presence of S. glossinidius on trypanosome presence in tsetse flies was studied in chapter 3. A high number of Sodalis positive flies was found in the Shimba Hills, while there were only two positive flies from Nguruman. Presence or absence of Sodalis was significantly associated with subpopulation while trypanosome presence showed a significant association with age (X2 = 4.65, df = 14, P-value = 0.0310) and an interaction between subpopulation and sex (X2 = 18.94, df = 10, P-value = 0.0043). However, the specific associations that were significant varied across species of trypanosomes, with T. congolense and T. brucei but not T. vivax showing significant interactions involving Sodalis. Although it has previously been concluded that presence of Sodalis increases susceptibility to trypanosomes, the results presented here suggest a more complicated relationship, which may be biased by differences in the distribution and intrinsic factors of tsetse flies, as well as which trypanosome species are considered. In chapter 4 trypanosome status was studied in relation to blood meal sources, feeding status and feeding patterns of G. pallidipes (which was the predominant fly species collected for this study) as determined by sequencing the mitochondrial cytochrome B gene using DNA extracted from abdomen samples. African buffalo and African elephants were the main sources of blood meals but antelopes, warthogs, humans, giraffes and hyenas were also identified. Feeding on multiple hosts was common in flies sampled from the Shimba Hills but most flies from Nguruman had fed on single host species. Based on Multiple Correspondence Analysis (MCA), host-feeding patterns showed a correlation with site of sample collection and Sodalis status, while trypanosome status was correlated with sex and age of the flies, suggesting that recent host-feeding patterns from blood meal analysis cannot predict trypanosome status. In conclusion, the complexity of interactions found suggests that strategies of tsetse fly control should be specific to particular epidemic areas. Future studies should include laboratory experiments that use local colonies of tsetse flies, local strains of trypanosomes and local S. glossinidius under controlled environmental conditions to tease out the factors that affect vector competence and the relative influence of external environmental factors on the dynamics of these interactions.

Empirical studies on share issuance and repurchase decisions

Financial constraints influence corporate policies of firms, including both investment decisions and external financing policies. The relevance of this phenomenon has become more pronounced during and after the recent financial crisis in 2007/2008. In addition to raising costs of external financing, the effects of financial crisis limited the availability of external financing which had implications for employment, investment, sale of assets, and tech spending. This thesis provides a comprehensive analysis of the effects of financial constraints on share issuance and repurchases decisions. Financial constraints comprise both internal constraints reflecting the demand for external financing and external financial constraints that relate to the supply of external financing. The study also examines both operating performance and stock market reactions associated with equity issuance methods. The first empirical chapter explores the simultaneous effects of financial constraints and market timing on share issuance decisions. Internal financing constraints limit firms’ ability to issue overvalued equity. On the other hand, financial crisis and low market liquidity (external financial constraints) restrict availability of equity financing and consequently increase the costs of external financing. Therefore, the study explores the extent to which internal and external financing constraints limit market timing of equity issues. This study finds that financial constraints play a significant role in whether firms time their equity issues when the shares are overvalued. The conclusion is that financially constrained firms issue overvalued equity when the external equity market or the general economic conditions are favourable. During recessionary periods, costs of external finance increase such that financially constrained firms are less likely to issue overvalued equity. Only unconstrained firms are more likely to issue overvalued equity even during crisis. Similarly, small firms that need cash flows to finance growth projects are less likely to access external equity financing during period of significant economic recessions. Moreover, constrained firms have low average stock returns compared to unconstrained firms, especially when they issue overvalued equity. The second chapter examines the operating performance and stock returns associated with equity issuance methods. Firms in the UK can issue equity through rights issues, open offers, and private placement. This study argues that alternative equity issuance methods are associated with a different level of operating performance and long-term stock returns. Firms using private placement are associated with poor operating performance. However, rights issues are found empirically to be associated with higher operating performance and less negative long-term stock returns after issuance in comparison to counterpart firms that issue private placements and open offers. Thus, rights issuing firms perform better than open offers and private placement because the favourable operating performance at the time of issuance generates subsequent positive long-run stock price response. Right issuing firms are of better quality and outperform firms that adopt open offers and private placement. In the third empirical chapter, the study explores the levered share repurchase of internally financially unconstrained firms. Unconstrained firms are expected to repurchase their shares using internal funds rather than through external borrowings. However, evidence shows that levered share repurchases are common among unconstrained firms. These firms display this repurchase behaviour when they have bond ratings or investment grade ratings that allow them to obtain cheap external debt financing. It is found that internally financially unconstrained firms borrow to finance their share repurchase when they invest more. Levered repurchase firms are associated with less positive abnormal returns than unlevered repurchase firms. For the levered repurchase sample, high investing firms are associated with more positive long-run abnormal stock returns than low investing firms. It appears the market underreact to the levered repurchase in the short-run regardless of the level of investments. These findings indicate that market reactions reflect both undervaluation and signaling hypotheses of positive information associated with share repurchase. As the firms undertake capital investments, they generate future cash flows, limit the effects of leverage on financial distress and ultimately reduce the risk of the equity capital.

Estimation of whole body muscle, adipose/fat mass, validation in health and during weight loss. Development of prediction equations using MRI as reference method

Background: Body composition is affected by diseases, and affects responses to medical treatments, dosage of medicines, etc., while an abnormal body composition contributes to the causation of many chronic diseases. While we have reliable biochemical tests for certain nutritional parameters of body composition, such as iron or iodine status, and we have harnessed nuclear physics to estimate the body’s content of trace elements, the very basic quantification of body fat content and muscle mass remains highly problematic. Both body fat and muscle mass are vitally important, as they have opposing influences on chronic disease, but they have seldom been estimated as part of population health surveillance. Instead, most national surveys have merely reported BMI and waist, or sometimes the waist/hip ratio; these indices are convenient but do not have any specific biological meaning. Anthropometry offers a practical and inexpensive method for muscle and fat estimation in clinical and epidemiological settings; however, its use is imperfect due to many limitations, such as a shortage of reference data, misuse of terminology, unclear assumptions, and the absence of properly validated anthropometric equations. To date, anthropometric methods are not sensitive enough to detect muscle and fat loss. Aims: The aim of this thesis is to estimate Adipose/fat and muscle mass in health disease and during weight loss through; 1. evaluating and critiquing the literature, to identify the best-published prediction equations for adipose/fat and muscle mass estimation; 2. to derive and validate adipose tissue and muscle mass prediction equations; and 3.to evaluate the prediction equations along with anthropometric indices and the best equations retrieved from the literature in health, metabolic illness and during weight loss. Methods: a Systematic review using Cochrane Review method was used for reviewing muscle mass estimation papers that used MRI as the reference method. Fat mass estimation papers were critically reviewed. Mixed ethnic, age and body mass data that underwent whole body magnetic resonance imaging to quantify adipose tissue and muscle mass (dependent variable) and anthropometry (independent variable) were used in the derivation/validation analysis. Multiple regression and Bland-Altman plot were applied to evaluate the prediction equations. To determine how well the equations identify metabolic illness, English and Scottish health surveys were studied. Statistical analysis using multiple regression and binary logistic regression were applied to assess model fit and associations. Also, populations were divided into quintiles and relative risk was analysed. Finally, the prediction equations were evaluated by applying them to a pilot study of 10 subjects who underwent whole-body MRI, anthropometric measurements and muscle strength before and after weight loss to determine how well the equations identify adipose/fat mass and muscle mass change. Results: The estimation of fat mass has serious problems. Despite advances in technology and science, prediction equations for the estimation of fat mass depend on limited historical reference data and remain dependent upon assumptions that have not yet been properly validated for different population groups. Muscle mass does not have the same conceptual problems; however, its measurement is still problematic and reference data are scarce. The derivation and validation analysis in this thesis was satisfactory, compared to prediction equations in the literature they were similar or even better. Applying the prediction equations in metabolic illness and during weight loss presented an understanding on how well the equations identify metabolic illness showing significant associations with diabetes, hypertension, HbA1c and blood pressure. And moderate to high correlations with MRI-measured adipose tissue and muscle mass before and after weight loss. Conclusion: Adipose tissue mass and to an extent muscle mass can now be estimated for many purposes as population or groups means. However, these equations must not be used for assessing fatness and categorising individuals. Further exploration in different populations and health surveys would be valuable.

Handle with care: historical geographies and difficult cultural legacies of egg-collecting

This thesis offers an examination of egg-collecting, which was a very popular pastime in Britain from the Victorian era well into the twentieth century. Collectors, both young and old, would often spend whole days and sometimes longer trips in a wide variety of different habitats, from sea shores to moorlands, wetlands to craggy mountainsides, searching for birds’ nests and the bounty to be found within them. Once collectors had found and taken eggs, they emptied out the contents; hence, they were really eggshell collectors. Some egg collectors claimed that egg-collecting was not just a hobby but a science, going by the name of oology, and seeking to establish oology as a recognised sub-discipline of ornithology, these collectors or oologists established formal institutions such as associations and societies, attended meetings where they exhibited unusual finds, and also contributed to specialist publications dedicated to oology. Egg-collecting was therefore many things at once: a culture of the British countryside, from where many eggs were taken; a culture of natural history, taking on the trappings of a science; and a culture of enthusiasm, providing a consuming passion for many collectors. By the early twentieth century, however, opposing voices were increasingly being raised, by conservation groups and other observers, about the impact that egg-collecting was having on bird populations and on the welfare of individual birds. By mid-century the tide had turned against the collectors, and egg-collecting in Britain was largely outlawed in 1954, with further restrictions imposed in 1981. While many egg collections have been lost or destroyed, some have been donated to museums, including Glasgow Museums (GM), which holds in its collections over 30,000 eggs. As a Collaborative Doctoral Award involving the University of Glasgow and GM, the project outlined in this thesis aims to bring to light and to life these egg collections, the activities of the collectors who originally built them, and the wider world of British egg-collecting. By researching archival material held by Glasgow Museums, published specialist egg-collecting journals and other published sources, as well as the eggs as a material archive, this thesis seeks to recover some of the practices and preoccupations of egg collectors. It also recounts the practical activities carried out during the course of the project at GM, particularly those involving a collection of eggs newly donated to the museum during the course of this project, culminating in a new temporary display of birds’ eggs at Glasgow Museums Resource Centre.