Statistical Analysis of the heavy neutral Atoms measured by IBEX

We investigate the directional distribution of heavy neutral atoms in the heliosphere by using heavy neutral maps generated with the IBEX-Lo instrument over three years from 2009 to 2011. The interstellar neutral (ISN) O&Ne gas flow was found in the first-year heavy neutral map at 601 keV and its flow direction and temperature were studied. However, due to the low counting statistics, researchers have not treated the full sky maps in detail. The main goal of this study is to evaluate the statistical significance of each pixel in the heavy neutral maps to get a better understanding of the directional distribution of heavy neutral atoms in the heliosphere. Here, we examine three statistical analysis methods: the signal-to-noise filter, the confidence limit method, and the cluster analysis method. These methods allow us to exclude background from areas where the heavy neutral signal is statistically significant. These methods also allow the consistent detection of heavy neutral atom structures. The main emission feature expands toward lower longitude and higher latitude from the observational peak of the ISN O&Ne gas flow. We call this emission the extended tail. It may be an imprint of the secondary oxygen atoms generated by charge exchange between ISN hydrogen atoms and oxygen ions in the outer heliosheath.

Search for Higgs Boson Production Beyond the Standard Model Using the Razor Kinematic Variables in pp Collisions at √s=8 TeV and Optimization of Higgs Boson Identification Using a Quantum Annealer

In the first part of this thesis we search for beyond the Standard Model physics through the search for anomalous production of the Higgs boson using the razor kinematic variables. We search for anomalous Higgs boson production using proton-proton collisions at center of mass energy √s=8 TeV collected by the Compact Muon Solenoid experiment at the Large Hadron Collider corresponding to an integrated luminosity of 19.8 fb^-1.

In the second part we present a novel method for using a quantum annealer to train a classifier to recognize events containing a Higgs boson decaying to two photons. We train that classifier using simulated proton-proton collisions at √s=8 TeV producing either a Standard Model Higgs boson decaying to two photons or a non-resonant Standard Model process that produces a two photon final state.

The production mechanisms of the Higgs boson are precisely predicted by the Standard Model based on its association with the mechanism of electroweak symmetry breaking. We measure the yield of Higgs bosons decaying to two photons in kinematic regions predicted to have very little contribution from a Standard Model Higgs boson and search for an excess of events, which would be evidence of either non-standard production or non-standard properties of the Higgs boson. We divide the events into disjoint categories based on kinematic properties and the presence of additional b-quarks produced in the collisions. In each of these disjoint categories, we use the razor kinematic variables to characterize events with topological configurations incompatible with typical configurations found from standard model production of the Higgs boson.

We observe an excess of events with di-photon invariant mass compatible with the Higgs boson mass and localized in a small region of the razor plane. We observe 5 events with a predicted background of 0.54 ± 0.28, which observation has a p-value of 10^-3 and a local significance of 3.35σ. This background prediction comes from 0.48 predicted non-resonant background events and 0.07 predicted SM higgs boson events. We proceed to investigate the properties of this excess, finding that it provides a very compelling peak in the di-photon invariant mass distribution and is physically separated in the razor plane from predicted background. Using another method of measuring the background and significance of the excess, we find a 2.5σ deviation from the Standard Model hypothesis over a broader range of the razor plane.

In the second part of the thesis we transform the problem of training a classifier to distinguish events with a Higgs boson decaying to two photons from events with other sources of photon pairs into the Hamiltonian of a spin system, the ground state of which is the best classifier. We then use a quantum annealer to find the ground state of this Hamiltonian and train the classifier. We find that we are able to do this successfully in less than 400 annealing runs for a problem of median difficulty at the largest problem size considered. The networks trained in this manner exhibit good classification performance, competitive with the more complicated machine learning techniques, and are highly resistant to overtraining. We also find that the nature of the training gives access to additional solutions that can be used to improve the classification performance by up to 1.2% in some regions.

Determinants of engagement in virtual social networks in Singapore

The use of virtual social networks (VSNs) has been prevalent among consumers worldwide. Numerous studies have investigated various aspects of VSNs. However, these studies have mainly focused on students and young adults as they were early adopters of these innovative networks. A search of the literature revealed there has been a paucity of research on adult consumers’ use of VSNs. This research study addressed this gap in the literature by examining the determinants of engagement in VSNs among adult consumers in Singapore. The objectives of this study are to empirically investigate the determinants of engagement in VSNs and to offer theoretical insights into consumers’ preference and usage of VSNs. This study tapped upon several theories developed in the discipline of technology and innovation adoption. These were Roger’s Diffusion of Innovation, Theory of Reasoned Action (TRA), Theory of Planned Behavior (TPB), Technology Acceptance Model (TAM), Conceptual Framework of Individual Innovation Adoption by Frambach and Schillewaert (2002), Enhanced Model of Innovation Adoption by Talukder (2011), Extended Unified Theory of Acceptance and Use of Technology (UTAUT2) and the Information Systems (IS) Success Model. The proposed research model, named the Media Usage Model (MUM), is a framework rooted in innovation diffusion and IS theories. The MUM distilled the essence of these established models and thus provides an updated, lucid explanation of engagement in VSNs. A cross-sectional, online social survey was conducted to collect quantitative data to examine the validity of the proposed research model. Multivariate data analysis was carried out on a data set comprising 806 usable responses by utilizing SPSS, and for structural equation modeling AMOS and SmartPLS. The results indicate that consumer attitude towards VSNs is significantly and positively influenced by: three individual factors – hedonic motivation, incentives and experience; two system characteristics – system quality and information quality; and one social factor – social bonding. Consumer demographics were found to influence people’s attitudes towards VSNs. In addition, consumer experience and attitude towards VSNs significantly and positively influence their usage of VSNs. The empirical data supported the proposed research model, explaining 80% of variance in attitude towards VSNs and 45% of variance in usage of VSNs. Therefore, the MUM achieves a definite contribution to theoretical knowledge of consumer engagement in VSNs by deepening and broadening our appreciation of the intricacies related to use of VSNs in Singapore. This study’s findings have implications for customer service management, services marketing and consumer behavior. These findings also have strategic implications for maximizing efficient utilization and effective management of VSNs by businesses and operators. The contributions of this research are: firstly, shifting the boundaries of technology or innovation adoption theories from research on employees to consumers as well as the boundaries of Internet usage or adoption research from students to adults, which is also known as empirical generalization; secondly, highlighting the issues associated with lack of significance of social factors in adoption research; and thirdly, augmenting information systems research by integrating important antecedents for success in information systems.

A retrospective observational study of low-level viraemia and its immunological and virological significance: which outcome to expect

This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The lived experience of volunteering in a palliative care biography service

OBJECTIVE: Many patients approaching death experience hopelessness, helplessness, and a depressed mood, and these factors can contribute to a difficult end-of-life (EoL) period. Biography services may assist patients in finding meaning and purpose at this time. The aim of our study was to investigate the lived experience of volunteers involved in a biography service in Melbourne, Australia, using a qualitative methodology. METHOD: The participants were 10 volunteers who had participated in a biography service within a private palliative care service. Each volunteer was interviewed separately using a study-specific semistructured interview guide. The transcripts of these interviews were then subjected to thematic analysis. RESULTS: Analysis yielded the following themes: motivations for volunteering; dealing with death, dying, and existential issues; psychosocial benefits of volunteering; and benefits and challenges of working with patients and their families. Our results indicated that volunteering gave the volunteers a deeper appreciation of existential issues, and helped them to be more appreciative of their own lives and gain a deeper awareness of the struggles other people experience. They also suggested that volunteers felt that their involvement contributed to their own personal development, and was personally rewarding. Furthermore, the results highlighted that volunteers found that encounters with family members were sometimes challenging. While some were appreciative, others imposed time limits, became overly reliant on the volunteers, and were sometimes offended, hurt, and angered by what was included in the final biography. SIGNIFICANCE OF RESULTS: It is hoped that the findings of the current study will provide direction for improvements in the biography services that will benefit patients, family members, and volunteers. In particular, our findings highlight the need to provide ongoing support for volunteers to assist them in handling the challenges of volunteering in a palliative care setting.

An investigation into the potential adoption of international financial reporting standards in the United States: implications and implementation

International Financial Reporting Standards (IFRS) have been adopted by most of the G20 countries. Given the broad worldwide acceptance of IFRS and significance of attaining comparability to facilitate free flow of capital, the US standard setter, the Financial Accounting Standards Board (FASB) made a commitment to jointly work with the International Accounting Standards Board (IASB) to explore the possibilities of convergence of US Generally Accepted Accounting Principles (GAAP) with IFRS. In 2007, the US Securities and Exchange Commission (SEC) eliminated the requirement that foreign companies listed on the US stock exchanges reconcile their IFRS-based financial statements with the US GAAP. In the same year the US SEC issued a concept release to the public requesting comments on a proposal to allow US issuers to prepare financial statements in accordance with IFRS. Following these initiatives by the FASB and SEC, the aim of the present study is to investigate the implications of a potential full adoption of IFRS by the US. The present study details the challenges and benefits of adoption and outlines the steps required for a successful outcome of this process.

The moderating role of firm age in the relationship between R&D expenditure and financial performance: evidence from Chinese and US mining firms

We examine the impact of Research and Development (R&D) on the profitability and sales of mining firms in China and the United States (US) and the moderating effect of firm age using Coarsened Exact Matching (CEM). For the combined panel of 168 major US and Chinese mining firms, we find that, on average, a firm engaging in R&D activities earns 4% to 11% higher sales and generates 4% to 13% more profits than firms that do not engage in R&D activities. We also show that, in the mining industry, firm age moderates the relationship between R&D activities and financial performance. A comparatively mature R&D active firm earns 4.4% more profit and generates 7.2% more sales than a younger non-innovative firm. The turning point at which R&D activities switch from making a negative, to positive, contribution to profit and sales is 37 years and 22 years, respectively. Our results are consistentwith the liability of newness, meaning that firm investment in R&D takes time to have a real impact on bottom line measures of financial performance. We conclude with a discussion of the practical implications of our results for Chinese and US mining firms.

The social life of historical neighbourhoods: case study of a Middle Eastern city, Shiraz

Historic neighbourhoods have usually shaped on an organic structure in regard to their residents’ requirements. Due to the limitations in mobility, historical neighbourhoods were usually able to perform as a small city comprising all the elements required for satisfying physical, social, and cultural needs. This paper seeks to explore the patterns of social life in the traditional settlements in Shiraz and investigate the elements that have shaped the social life of these neighbourhoods. Exploring the social structure of historic neighbourhoods may introduce new approaches to the design of contemporary suburbs and neighbourhoods in terms of their vitality and social life. A review of the literature and comparing it to the historical core in Shiraz shows that there are five contributing factors to the social life of historic neighbourhoods in Shiraz, including density, human scale development, walkability, mixed land-use and qualities of public spaces. Exploring the features of public places and communal facilities indicates that the fine social performance of these settlements is rooted in their compatibility and adaptability to the environment, the residents’ requirements and culture.

Legal risk impact in Public Private Partnerships (PPPs): the case of the Chinese water sector

China is currently experiencing a rising demand for water, combined with limited funding availability for water project procurement. Consequently, local Chinese governments have sought procurement solutions by experimenting with public private partnerships (PPPs). However, the legal risk in PPPs, particularly in the water sector, remains high. Legal risk refers to risk arising from the legal and regulatory systems surrounding PPPs. Past research have identified legal risk in PPP projects in China as critical, however the stages at which they are significant have not been studied. This paper examines the legal risk associated with PPPs in the water sector in China and measures the degree of risk across three key stages; 1) Procurement, 2) Construction and 3) Operation. The interrelationship between legal risk at these three stages is also investigated. The significance of the risk was measured by determining the probability and severity of the risk. Correlation analysis was used to investigate the relationship between legal risks across the three stages. Our findings are that legal risk is present at all three stages, at close to moderate levels, with risk significance greatest at the operational stage. Moreover, while no correlation was identified for legal risk at the operational stage with those of earlier stages, it was found that legal issues arising during the procurement stage significantly exacerbated any further legal issues that emerged during the construction stage of water projects. The findings from this study will be significant in providing practitioners with the information to manage this risk at different stages of PPP projects.

MINING AND VERIFICATION OF TEMPORAL EVENTS WITH APPLICATIONS IN COMPUTER MICRO-ARCHITECTURE RESEARCH

Computer simulation programs are essential tools for scientists and engineers to understand a particular system of interest. As expected, the complexity of the software increases with the depth of the model used. In addition to the exigent demands of software engineering, verification of simulation programs is especially challenging because the models represented are complex and ridden with unknowns that will be discovered by developers in an iterative process. To manage such complexity, advanced verification techniques for continually matching the intended model to the implemented model are necessary. Therefore, the main goal of this research work is to design a useful verification and validation framework that is able to identify model representation errors and is applicable to generic simulators. The framework that was developed and implemented consists of two parts. The first part is First-Order Logic Constraint Specification Language (FOLCSL) that enables users to specify the invariants of a model under consideration. From the first-order logic specification, the FOLCSL translator automatically synthesizes a verification program that reads the event trace generated by a simulator and signals whether all invariants are respected. The second part consists of mining the temporal flow of events using a newly developed representation called State Flow Temporal Analysis Graph (SFTAG). While the first part seeks an assurance of implementation correctness by checking that the model invariants hold, the second part derives an extended model of the implementation and hence enables a deeper understanding of what was implemented. The main application studied in this work is the validation of the timing behavior of micro-architecture simulators. The study includes SFTAGs generated for a wide set of benchmark programs and their analysis using several artificial intelligence algorithms. This work improves the computer architecture research and verification processes as shown by the case studies and experiments that have been conducted.

Preserving and interpreting the mining company office : landscape, space and technological change in the management of the copper industry

The purpose of this research is to examine the role of the mining company office in the management of the copper industry in Michigan’s Keweenaw Peninsula between 1901 and 1946. Two of the largest and most influential companies were examined – the Calumet & Hecla Mining Company and the Quincy Mining Company. Both companies operated for more than forty years under general managers who were arguably the most influential people in the management of each company. James MacNaughton, general manager at Calumet and Hecla, worked from 1901 through 1941; Charles Lawton, general manager at Quincy Mining Company, worked from 1905 through 1946. In this case, both of these managers were college-educated engineers and adopted scientific management techniques to operate their respective companies. This research focused on two main goals. The first goal of this project was to address the managerial changes in Michigan’s copper mining offices of the early twentieth century. This included the work of MacNaughton and Lawton, along with analysis of the office structures themselves and what changes occurred through time. The second goal of the project was to create a prototype virtual exhibit for use at the Quincy Mining Company office. A virtual exhibit will allow visitors the opportunity to visit the office virtually, experiencing the office as an office worker would have in the early twentieth century. To meet both goals, this project used various research materials, including archival sources, oral histories, and material culture to recreate the history of mining company management in the Copper Country.

A Multi-Criteria GIS-Based Route Selection Tool for Hazardous Material Transport: Consideration of Environmental Consequence, Traffic Congestions and Costs

Hazardous materials are substances that, if not regulated, can pose a threat to human populations and their environmental health, safety or property when transported in commerce. About 1.5 million tons of hazardous material shipments are transported by truck in the US annually, with a steady increase of approximately 5% per year. The objective of this study was to develop a routing tool for hazardous material transport in order to facilitate reduced environmental impacts and less transportation difficulties, yet would also find paths that were still compelling for the shipping carriers as a matter of trucking cost. The study started with identification of inhalation hazard impact zones and explosion protective areas around the location of hypothetical hazardous material releases, considering different parameters (i.e., chemicals characteristics, release quantities, atmospheric condition, etc.). Results showed that depending on the quantity of release, chemical, and atmospheric stability (a function of wind speed, meteorology, sky cover, time and location of accidents, etc.) the consequence of these incidents can differ. The study was extended by selection of other evaluation criteria for further investigation because health risk as an evaluation criterion would not be the only concern in selection of routes. Transportation difficulties (i.e., road blockage and congestion) were incorporated as important factor due to their indirect impact/cost on the users of transportation networks. Trucking costs were also considered as one of the primary criteria in selection of hazardous material paths; otherwise the suggested routes would have not been convincing for the shipping companies. The last but not least criterion was proximity of public places to the routes. The approach evolved from a simple framework to a complicated and efficient GIS-based tool able to investigate transportation networks of any given study area, and capable of generating best routing options for cargos. The suggested tool uses a multi-criteria-decision-making method, which considers the priorities of the decision makers in choosing the cargo routes. Comparison of the routing options based on each criterion and also the overall suitableness of the path in regards to all the criteria (using a multi-criteria-decision-making method) showed that using similar tools as the one proposed by this study can provide decision makers insights in the area of hazardous material transport. This tool shows the probable consequences of considering each path in a very easily understandable way; in the formats of maps and tables, which makes the tradeoffs of costs and risks considerably simpler, as in some cases slightly compromising on trucking cost may drastically decrease the probable health risk and/or traffic difficulties. This will not only be rewarding to the community by making cities safer places to live, but also can be beneficial to shipping companies by allowing them to advertise as environmental friendly conveyors.

Ethno-architecture and the politics of migration

Ethno-Architecture and the Politics of Migration explores the interface between migration and architecture. Cities have been substantially affected by transnational migration but the physical manifestations of migration in architecture and its effect on streetscape, neighbourhood and city – have so far been under-studied. This contributed volume examines how migrants interact with, adapt and construct new architecture. Looking at the physical, urban and cultural impact of these changes on a variety of sites, the authors explore architecture as an identity category and investigate what buildings and places associated with migration tell us about central questions of belonging, culture, community and home in regions such as North America, Australia and the UK. This book makes an important contribution to debates on place identity and the transformation of places as a result of mobility and globalised economies in the twenty-first century.

The patient experience of a peripherally inserted central catheter (PICC): A qualitative descriptive study.

UNLABELLED: Abstract Aim: To investigate the patient experience of Peripherally Inserted Central Catheter (PICC) insertion, the significance of arm choice and the impact of the device on activities of daily living. BACKGROUND: Arm choice for PICC insertion is often determined by PICC nurses with little input from consumers. There are few studies that have investigated the patient experience of living with a PICC and none that have examined the impact of arm choice from the consumer's perspective. METHOD: Participants were recruited in a hospital whilst they waited for PICC insertion. A purposeful sampling approach was used to select participants based on diagnosis types. Semi-structured telephone interviews were conducted November 2012-August 2013. Transcripts of the interviews were analysed using thematic analysis. FINDINGS: Ten participants were interviewed. Four themes were identified: (i) apprehension/adaptation/acceptance, (ii) impact of treatment, (iii) asking questions (trusting doctors) and (iv) freedom. Although initially apprehensive, participants adapted to the PICC and came to accept that the device allowed convenient access for treatment. This allowed them the freedom to receive treatment at home. The use of the dominant or non-dominant arm for PICC insertion had marginal impact on activities of daily living for participants. Auxiliary factors such as the infusion pump had a significant impact for those who received outpatient treatment. For those participants who did not understand the procedure, many did not seek clarification and trusted medical and nursing staff to make decisions for them. CONCLUSION: Nurses should involve consumers in clinical decision-making and provide individualised information and support that facilitates adaptation for patients living with a PICC.

Investigating Angiotensin II in cardiac remodelling and the counter-regulatory actions of Angiotensin-(1-9)

Cardiovascular diseases (CVDs) including, hypertension, coronary heart disease and heart failure are the leading cause of death worldwide. Hypertension, a chronic increase in blood pressure above 140/90 mmHg, is the single main contributor to deaths due to heart disease and stroke. In the heart, hypertension results in adaptive cardiac remodelling, including LV hypertrophy to normalize wall stress and maintain cardiac contractile function. However, chronic increases in BP results in the development of hypertensive heart disease (HHD). HHD describes the maladaptive changes during cardiac remodelling which result in reduced systolic and diastolic function and eventually heart failure. This includes ventricular dilation due to eccentric hypertrophy, cardiac fibrosis which stiffens the ventricular wall and microvascular rarefaction resulting in a decrease in coronary blood flow albeit an increase in energy demand. Chronic activation of the renin-angiotensin-system (RAS) with its effector peptide angiotensin (Ang)II plays a key role in the development of hypertension and the maladaptive changes in HHD. Ang II acts via the angiotensin type 1 receptor (AT1R) to mediate most of its pathological actions during HHD, including stimulation of cardiomyocyte hypertrophy, activation of cardiac fibroblasts and increased collagen deposition. The counter-regulatory axis of the RAS which is centred on the ACE2/Ang-(1-7)/Mas axis has been demonstrated to counteract the pathological actions of Ang II in the heart and vasculature. Ang-(1-7) via the Mas receptor prevents Ang II-induced cardiac hypertrophy and fibrosis and improves cardiac contractile function in animal models of HHD. In contrast, less is known about Ang-(1-9) although evidence has demonstrated that Ang-(1-9) also antagonises Ang II and is anti-hypertrophic and anti-fibrotic in animal models of acute cardiac remodelling. However, so far it is not well documented whether Ang-(1-9) can reverse established cardiac dysfunction and remodelling and whether it is beneficial when administered chronically. Therefore, the main aim of this thesis was to assess the effects of chronic Ang-(1-9) administration on cardiac structure and function in a model of Ang II-induced cardiac remodelling. Furthermore, this thesis aimed to investigate novel pathways contributing to the pathological remodelling in response to Ang II. First, a mouse model of chronic Ang II infusion was established and characterised by comparing the structural and functional effects of the infusion of a low and high dose of Ang II after 6 weeks. Echocardiographic measurements demonstrated that low dose Ang II infusion resulted in a gradual decline in cardiac function while a high dose of Ang II induced acute cardiac contractile dysfunction. Both doses equally induced the development of cardiac hypertrophy and cardiac fibrosis characterised by an increase in the deposition of collagen I and collagen III. Moreover, increases in gene expression of fibrotic and hypertrophic markers could be detected following high dose Ang II infusion over 6 weeks. Following this characterisation, the high dose infusion model was used to assess the effects of Ang-(1-9) on cardiac structural and functional remodelling in established disease. Initially, it was evaluated whether Ang-(1-9) can reverse Ang II-induced cardiac disease by administering Ang-(1-9) for 2-4 weeks following an initial 2 week infusion of a high dose of Ang II to induce cardiac contractile dysfunction. The infusion of Ang-(1-9) for 2 weeks was associated with a significant improvement of LV fractional shortening compared to Ang II infusion. However, after 4 weeks fractional shortening declined to Ang II levels. Despite the transient improvement in cardiac contractile function, Ang-(1-9) did not modulate blood pressure, LV hypertrophy or cardiac fibrosis. To further investigate the direct cardiac effects of Ang-(1-9), cardiac contractile performance in response to Ang-(1-9) was evaluated in the isolated Langendorff-perfused rat heart. Perfusion of Ang-(1-9) in the paced and spontaneously beating rat heart mediated a positive inotropic effect characterised by an increase in LV developed pressure, cardiac contractility and relaxation. This was in contrast to Ang II and Ang-(1-7). Furthermore, the positive inotropic effect to Ang-(1-9) was blocked by the AT1R antagonist losartan and the protein kinase A inhibitor H89. Next, endothelial-to-mesenchymal transition (EndMT) as a novel pathway that may contribute to Ang II-induced cardiac remodelling was assessed in Ang II-infused mice in vivo and in human coronary artery endothelial cells (HCAEC) in vitro. Infusion of Ang II to mice for 2-6 weeks resulted in a significant decrease in myocardial capillary density and this was associated with the occurrence of dual labelling of endothelial cells for endothelial and mesenchymal markers. In vitro stimulation of HCAEC with TGFβ and Ang II revealed that Ang II exacerbated TGF-induced gene expression of mesenchymal markers. This was not correlated with any changes in SMAD2 or ERK1/2 phosphorylation with co-stimulation of TGFβ and Ang II. However, superoxide production was significantly increased in HCAEC stimulated with Ang II but not TGFβ. Finally, the role of Ang II in microvesicle (MV)-mediated cardiomyocyte hypertrophy was investigated. MVs purified from neonatal rat cardiac fibroblasts were found to contain detectable Ang II and this was increased by stimulation of fibroblasts with Ang II. Treatment of cardiomyocytes with MVs derived from Ang II-stimulated fibroblasts induced cardiomyocyte hypertrophy which could be blocked by the AT1R antagonist losartan and an inhibitor of MV synthesis and release brefeldin A. Furthermore, Ang II was found to be present in MVs isolated from serum and plasma of Ang II-infused mice and SHRSP and WKY rats. Overall, the findings of this thesis demonstrate for the first time that the actions of Ang-(1-9) in cardiac pathology are dependent on its time of administration and that Ang-(1-9) can reverse Ang II-induced cardiac contractile dysfunction by acting as a positive inotrope. Furthermore, this thesis demonstrates evidence for an involvement of EndMT and MV signalling as novel pathways contributing to Ang II-induced cardiac fibrosis and hypertrophy, respectively. These findings provide incentive to further investigate the therapeutic potential of Ang-(1-9) in the treatment of cardiac contractile dysfunction in heart disease, establish the importance of novel pathways in Ang II-mediated cardiac remodelling and evaluate the significance of the presence of Ang II in plasma-derived MVs.