The Ultrastructural and Abnormal Calcium Handling in Pulmonary Vein Sleeve Cells, Atrial and Ventricular Myocytes During Ageing

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with age being a significant risk factor. It is well established now that electric activities originating from pulmonary vein sleeve cells (PVCs) initiate AF. Factors that are involved in maintaining AF include structural remodelling and abnormal Ca2+ handling in PVCs and atrial myocytes. Whilst structural changes and alterations in the Ca2+ homeostasis have been described previously in atrial myocytes, similar studies are still lacking in PVCs. Thus, this thesis investigated structural remodelling and Ca2+ handling, particularly in PVCs from 3- and 24month-old mice. Using immunohistochemical and electron microscopy (EM) studies, this thesis revealed that PVCs just like atrial and ventricular myocytes, express RyR2, Cx40, and Cx43. Whilst RyR2 and Cx43 expressions did not change with age, Cx40 expression was found to deteriorate during ageing. Additionally, EM studies showed significant alterations in mitochondria which increased in size and numbers during ageing. Unlike PVCs, mitochondria in atrial myocytes were enlarged but did not increase in numbers during ageing. Mitochondria in ventricular myocytes did not deteriorate with age.This study also showed that Ca2+ homeostasis in PVCs is disrupted during ageing. PVCs from aged mice had an increased frequency and duration of spontaneous Ca2+ waves, with reduced amplitude, less able to follow electrical pacing and had higher basal ROS levels compared to PVCs from young mice.Additional studies attempted to induce ageing chemically with hydroxyurea (HU) in neonatal rat ventricular myocytes (NRVMs). HU inhibited pacing ability, induced autophagy and increased inducible ROS. Although some changes in chemically ageing model were similar to those in aged PVCs, further studies are needed to fully establish whether HU can induce ageing in NRVMs.In conclusion, this study showed that structural remodelling and Ca2+ homeostasis differs in PVCs during ageing which may facilitate the occurrence of arrhythmias

The implications of legal change and political reform for the workings of the Majlis A' Shura and Majlis A' Dawlah in Oman (1981-2003)

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The Impact of Foreign Aid on Economic Growth of East African Countries

In this paper, we employ panel data methods, namely Pooled OLS, Random Effects, and Fixed Effects, to examine the impact of foreign aid on economic growth of East African countries over the period of 1985 to 2010. The results suggest that foreign aid has significant negative influence on economic growth for these countries. This calls for further studies to investigate the possible channels through which foreign aid can have positive influence on growth. Keywords: EAC countries, Foreign aid, Panel data approac

Export Trade and Economic Growth in Tanzania: A Disaggregated Approach

This paper applies the Vector Autoregressive (VAR) technique to annual data from 1980 to 2009 to provide empirical evidence on the long-run relationship between exports trade and economic growth in Tanzania. The exports trade in this study is disaggregated into services and goods exports. Thus, the paper estimated two models. The first model deals with the relationship between export of services and growth, and the other one determines the relationship between goods export and growth. While the paper find no evidence for long-run relationship between export of goods and growth, our empirical results suggest existence of a long-run nexus between export of services and economic growth in Tanzania. The Granger causality test results have also confirmed existence of a unilateral causality from economic growth to service exports. Keywords: Export Trade; Economic Growth; Cointegration; Granger Causality.

Community-Oriented Models and Applications for the Social Web

The past few years have seen the rapid rise of all things "social" on the web from the growth of online social networks like Facebook, to user-contributed content sites like Flickr and YouTube, to social bookmarking services like Delicious, among many others. Whereas traditional approaches to organizing and accessing the web’s massive amount of information have focused on content-based and link-based approaches, these social systems offer rich opportunities for user-based and community-based exploration and analysis of the web by building on the unprecedented access to the interests and perspectives of millions of users. We focus here on the challenge of modeling and mining social bookmarking systems, in which resources are enriched by large-scale socially generated metadata (“tags”) and contextualized by the user communities that are associated with the resources. Our hypothesis is that an underlying social collective intelligence is embedded in the uncoordinated actions of users on social bookmarking services, and that this social collective intelligence can be leveraged for enhanced web-based information discovery and knowledge sharing. Concretely, we posit the existence of underlying implicit communities in these social bookmarking systems that drive the social bookmarking process which can provide a foundation for community-based organization of web resources. To that end, we make three contributions: • First, we propose a pair of novel probabilistic generative models for describing and modeling community-oriented social bookmarking. We show how these models enable effective extraction of meaningful communities over large real world social bookmarking services. • Second, we develop two frameworks for community-based web information browsing and search that are based on these community-oriented social bookmarking models. We show how both achieve improved discovery and exploration of the social web. • Third, we introduce a community evolution framework for studying and analyzing social bookmarking communities over time. We explore the temporal dimension of social bookmarking and explore the dynamics of community formation, evolution, and dissolution. By uncovering implicit communities, putting them to use in an application scenario (search and browsing), and analyzing them over time, this dissertation provides a foundation for the study of how social knowledge networks are self-organized, a deeper understanding and appreciation of the factors impacting collective intelligence, and the creation of new information access algorithms for leveraging these communities

Formulation and a two-phase matheuristic for the roaming salesman problem: Application to election logistics

In this paper we investigate a novel logistical problem. The goal is to determine daily tours for a traveling salesperson who collects rewards from activities in cities during a fixed campaign period. We refer to this problem as the Roaming Salesman Problem (RSP) motivated by real-world applications including election logistics, touristic trip planning and marketing campaigns. RSP can be characterized as a combination of the traditional Periodic TSP and the Prize-Collecting TSP with static arc costs and time-dependent node rewards. Commercial solvers are capable of solving small-size instances of the RSP to near optimality in a reasonable time. To tackle large-size instances we propose a two-phase matheuristic where the first phase deals with city selection while the second phase focuses on route generation. The latter capitalizes on an integer program to construct an optimal route among selected cities on a given day. The proposed matheuristic decomposes the RSP into as many subproblems as the number of campaign days. Computational results show that our approach provides near-optimal solutions in significantly shorter times compared to commercial solvers

Examining Cardiomyocyte Dysfunction Using Acute Chemical Induction of an Ageing Phenotype

Much effort is focussed on understanding the structural and functional changes in the heart that underlie age-dependent deterioration of cardiac performance. Longitudinal studies, using aged animals, have pinpointed changes occurring to the contractile myocytes within the heart. However, whilst longitudinal studies are important, other experimental approaches are being advanced that can recapitulate the phenotypic changes seen during ageing. This study investigated the induction of an ageing cardiomyocyte phenotypic change by incubation of cells with hydroxyurea for several days ex vivo. Hydroxyurea incubation has been demonstrated to phenocopy age- and senescence-induced changes in neurons, but its utility for ageing studies with cardiac cells has not been examined. Incubation of neonatal rat ventricular myocytes with hydroxyurea for up to 7 days replicated specific aspects of cardiac ageing including reduced systolic calcium responses, increased alternans and a lesser ability of the cells to follow electrical pacing. Additional functional and structural changes were observed within the myocytes that pointed to ageing-like remodelling, including lipofuscin granule accumulation, reduced mitochondrial membrane potential, increased production of reactive oxygen species, and altered ultrastructure, such as mitochondria with disrupted cristae and disorganised myofibres. These data highlight the utility of alternative approaches for exploring cellular ageing whilst avoiding the costs and co-morbid factors that can affect longitudinal studies

Bacteraemia, Malaria, and Case Fatality Among Children Hospitalized With Fever in Dar es Salaam, Tanzania

Background Febrile illness is the commonest cause of hospitalization in children <5 years in sub-Saharan Africa, and bacterial blood stream-infections and malaria are major causes of death. Methods From March 2017 to July 2018, we enrolled 2226 children aged 0-5 years hospitalized due to fever in four major public hospitals of Dar es Salaam namely; Amana, Temeke and Mwananyamala Regional Hospitals and Muhimbili National Hospital. We recorded social demographic and clinical data, performed blood-culture and HIV-antibody testing. We used qPCR to quantify Plasmodium falciparum parasitaemia and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) to identify bacterial isolates. Disk diffusion method was used for antimicrobial susceptibility testing. Results Nineteen percent of the children (426/2226) had pathogens detected from blood. Eleven percent (236/2226) of the children had bacteraemia/fungaemia and 10% (204/2063) had P. falciparum malaria. Ten children had concomitant malaria and bacteraemia. Gram-negative bacteria (64%) were more frequent than Gram-positive (32%) and fungi (4%). Over fifty percent of Gram-negative bacteria were extended-spectrum beta-lactamase (ESBL) producers and multidrug resistant. Methicillin resistant Staphylococcus aureus (MRSA) was found in 11/42 (26.2%). The most severe form of clinical malaria was associated with high parasitaemia (>four million genomes/µL) of P. falciparaum in plasma. Overall, in-hospital death was 4% (89/2146) and it was higher in children with bacteraemia (8%, 18/227) than malaria (2%, 4/194, P=0.007). Risk factors for death were bacteraemia (p=0.03), unconsciousness at admission (p<0.001) and admission at a tertiary hospital (p=0.003). Conclusions Compared to previous studies in this region, our study showed a reduction in malaria prevalence, a decrease in in-hospital mortality and an increase in antimicrobial resistance (AMR) including ESBLs and multidrug resistance. An increase of AMR highlights the importance of continued strengthening of diagnostic capability and antimicrobial stewardship programs. We also found malaria and bacteraemia contributed equally in causing febrile illness but bacteraemia caused higher in-hospital death. The most severe form of clinical malaria was associated with P. falciparum parasitaemia