Volunteering for the Commonwealth Games: what can realist synthesis contribute to health policy making?

The aim of this thesis was to investigate, using the real-time test case of the 2014 Commonwealth Games, whether the realist synthesis methodology could contribute to the making of health policy in a meaningful way. This was done by looking at two distinct research questions: first, whether realist synthesis could contribute new insights to the health policymaking process, and second, whether the 2014 Commonwealth Games volunteer programme was likely to have any significant, measurable, impact on health inequalities experienced by large sections of the host population. The 2014 Commonwealth Games legacy laid out ambitious plans for the event, in which it was anticipated that it would provide explicit opportunities to impact positively on health inequalities. By using realist synthesis to unpick the theories underpinning the volunteer programme, the review identifies the population subgroups for whom the programme was likely to be successful, how this could be achieved and in what contexts. In answer to the first research question, the review found that while realist methods were able to provide a more nuanced exposition of the impacts of the Games volunteer programme on health inequalities than previous traditional reviews had been able to provide, there were several drawbacks to using the method. It was found to be resource-intensive and complex, encouraging the exploration of a much wider set of literatures at the expense of an in-depth grasp of the complexities of those literatures. In answer to the second research question, the review found that the Games were, if anything, likely to exacerbate health inequalities because the programme was designed in such a way that individuals recruited to it were most likely to be those in least need of the additional mental and physical health benefits that Games volunteering was designed to provide. The following thesis details the approach taken to investigate both the realist approach to evidence synthesis and the likelihood that the 2014 Games volunteer programme would yield the expected results.

Oxidative stress and its haemodynamic consequences in chronic kidney disease

Chronic kidney disease (CKD) is associated with increased cardiovascular risk in comparison with the general population. This can be observed even in the early stages of CKD, and rises in proportion to the degree of renal impairment. Not only is cardiovascular disease (CVD) more prevalent in CKD, but its nature differs too, with an excess of morbidity and mortality associated with congestive cardiac failure, arrhythmia and sudden death, as well as the accelerated atherosclerosis which is also observed. Conventional cardiovascular risk factors such as hypertension, dyslipidaemia, obesity, glycaemia and smoking, are highly prevalent amongst patients with CKD, although in many of these examples the interaction between risk factor and disease differs from that which exists in normal renal function. Nevertheless, the extent of CVD cannot be fully explained by these conventional risk factors, and non-conventional factors specific to CKD are now recognised to contribute to the burden of CVD. Oxidative stress is a state characterised by excessive production of reactive oxygen species (ROS) and other radical species, a reduction in the capacity of antioxidant systems, and disturbance in normal redox homeostasis with depletion of protective vascular signalling molecules such as nitric oxide (NO). This results in oxidative damage to macromolecules such as lipids, proteins and DNA which can alter their functionality. Moreover, many enzymes are sensitive to redox regulation such that oxidative modification to cysteine thiol groups results in activation of signalling cascades which result in adverse cardiovascular effects such as vascular and endothelial dysfunction. Endothelial dysfunction and oxidative stress are present in association with many conventional cardiovascular risk factors, and can be observed even prior to the development of overt, clinical, vascular pathology, suggesting that these phenomena represent the earliest stages of CVD. In the presence of CKD, there is increased ROS production due to upregulated NADPH oxidase (NOX), increase in a circulating asymmetric dimethylarginine (ADMA), uncoupling of endothelial nitric oxide synthase (eNOS) as well as other mechanisms. There is also depletion in exogenous antioxidants such as ascorbic acid and tocopherol, and a reduction in activity of endogenous antioxidant systems regulated by the master gene regulator Nrf-2. In previous studies, circulating markers of oxidative stress have been shown to be increased in CKD, together with a reduction in endothelial function in a stepwise fashion relating to the severity of renal impairment. Not only is CVD linked to oxidative stress, but the progression of CKD itself is also in part dependent on redox sensitive mechanisms. For example, administration of the ROS scavenger tempol attenuates renal injury and reduces renal fibrosis seen on biopsy in a mouse model of CKD, whilst conversely, supplementation with the NOS inhibitor L-NAME causes proteinuria and renal impairment. Previous human studies examining the effect of antioxidant administration on vascular and renal function have been conflicting however. The work contained in this thesis therefore examines the effect of antioxidant administration on vascular and endothelial function in CKD. Firstly, 30 patients with CKD stages 3 – 5, and 20 matched hypertensive controls were recruited. Participants with CKD had lower ascorbic acid, higher TAP and ADMA, together with higher augmentation index and pulse wave velocity. There was no difference in baseline flow mediated dilatation (FMD) between groups. Intravenous ascorbic acid increased TAP and O2-, and reduced central BP and augmentation index in both groups, and lowered ADMA in the CKD group only. No effect on FMD was observed. The effects of ascorbic acid on kidney function was then investigated, however this was hindered by the inherent drawbacks of existing methods of non-invasively measuring kidney function. Arterial spin labelling MRI is an emerging imaging technique which allows measurement of renal perfusion without administration of an exogenous contrast agent. The technique relies upon application of an inversion pulse to blood within the vasculature proximal to the kidneys, which magnetically labels protons allowing measurement upon transit to the kidney. At the outset of this project local experience using ASL MRI was limited and there ensued a prolonged pre-clinical phase of testing with the aim of optimising imaging strategy. A study was then designed to investigate the repeatability of ASL MRI in a group of 12 healthy volunteers with normal renal function. The measured T1 longitudinal relaxation times and ASL MRI perfusion values were in keeping with those found in the literature; T1 time was 1376 ms in the cortex and 1491 ms in the whole kidney ROI, whilst perfusion was 321 mL/min/100g in the cortex, and 228 mL/min/100g in the whole kidney ROI. There was good reproducibility demonstrated on Bland Altman analysis, with a CVws was 9.2% for cortical perfusion and 7.1% for whole kidney perfusion. Subsequently, in a study of 17 patients with CKD and 24 healthy volunteers, the effects of ascorbic acid on renal perfusion was investigated. Although no change in renal perfusion was found following ascorbic acid, it was found that ASL MRI demonstrated significant differences between those with normal renal function and participants with CKD stages 3 – 5, with increased cortical and whole kidney T1, and reduced cortical and whole kidney perfusion. Interestingly, absolute perfusion showed a weak but significant correlation with progression of kidney disease over the preceding year. Ascorbic acid was therefore shown to have a significant effect on vascular biology both in CKD and in those with normal renal function, and to reduce ADMA only in patients with CKD. ASL MRI has shown promise as a non-invasive investigation of renal function and as a biomarker to identify individuals at high risk of progressive renal impairment.

Query routing in cooperative semi-structured peer-to-peer information retrieval networks

Conventional web search engines are centralised in that a single entity crawls and indexes the documents selected for future retrieval, and the relevance models used to determine which documents are relevant to a given user query. As a result, these search engines suffer from several technical drawbacks such as handling scale, timeliness and reliability, in addition to ethical concerns such as commercial manipulation and information censorship. Alleviating the need to rely entirely on a single entity, Peer-to-Peer (P2P) Information Retrieval (IR) has been proposed as a solution, as it distributes the functional components of a web search engine – from crawling and indexing documents, to query processing – across the network of users (or, peers) who use the search engine. This strategy for constructing an IR system poses several efficiency and effectiveness challenges which have been identified in past work. Accordingly, this thesis makes several contributions towards advancing the state of the art in P2P-IR effectiveness by improving the query processing and relevance scoring aspects of a P2P web search. Federated search systems are a form of distributed information retrieval model that route the user’s information need, formulated as a query, to distributed resources and merge the retrieved result lists into a final list. P2P-IR networks are one form of federated search in routing queries and merging result among participating peers. The query is propagated through disseminated nodes to hit the peers that are most likely to contain relevant documents, then the retrieved result lists are merged at different points along the path from the relevant peers to the query initializer (or namely, customer). However, query routing in P2P-IR networks is considered as one of the major challenges and critical part in P2P-IR networks; as the relevant peers might be lost in low-quality peer selection while executing the query routing, and inevitably lead to less effective retrieval results. This motivates this thesis to study and propose query routing techniques to improve retrieval quality in such networks. Cluster-based semi-structured P2P-IR networks exploit the cluster hypothesis to organise the peers into similar semantic clusters where each such semantic cluster is managed by super-peers. In this thesis, I construct three semi-structured P2P-IR models and examine their retrieval effectiveness. I also leverage the cluster centroids at the super-peer level as content representations gathered from cooperative peers to propose a query routing approach called Inverted PeerCluster Index (IPI) that simulates the conventional inverted index of the centralised corpus to organise the statistics of peers’ terms. The results show a competitive retrieval quality in comparison to baseline approaches. Furthermore, I study the applicability of using the conventional Information Retrieval models as peer selection approaches where each peer can be considered as a big document of documents. The experimental evaluation shows comparative and significant results and explains that document retrieval methods are very effective for peer selection that brings back the analogy between documents and peers. Additionally, Learning to Rank (LtR) algorithms are exploited to build a learned classifier for peer ranking at the super-peer level. The experiments show significant results with state-of-the-art resource selection methods and competitive results to corresponding classification-based approaches. Finally, I propose reputation-based query routing approaches that exploit the idea of providing feedback on a specific item in the social community networks and manage it for future decision-making. The system monitors users’ behaviours when they click or download documents from the final ranked list as implicit feedback and mines the given information to build a reputation-based data structure. The data structure is used to score peers and then rank them for query routing. I conduct a set of experiments to cover various scenarios including noisy feedback information (i.e, providing positive feedback on non-relevant documents) to examine the robustness of reputation-based approaches. The empirical evaluation shows significant results in almost all measurement metrics with approximate improvement more than 56% compared to baseline approaches. Thus, based on the results, if one were to choose one technique, reputation-based approaches are clearly the natural choices which also can be deployed on any P2P network.