4,973 research outputs found

    Mathematical models to evaluate the impact of increasing serotype coverage in pneumococcal conjugate vaccines

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    Of over 100 serotypes of Streptococcus pneumoniae, only 7 were included in the first pneumo- coccal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation. This thesis has four aims. First, to explore the limitations and assumptions of published pneu- mococcal models and the implications for future vaccine formulation and policy. Second, to conduct a trend analysis assembling all the available evidence for serotype replacement in Europe, North America and Australia to characterise invasive pneumococcal disease (IPD) caused by vaccine-type (VT) and non-vaccine-types (NVT) serotypes. The motivation behind this is to assess the patterns of relative abundance in IPD cases pre- and post-vaccination, to examine country-level differences in relation to the vaccines employed over time since introduction, and to assess the growth of the replacement serotypes in comparison with the serotypes targeted by the vaccine. The third aim is to use a Bayesian framework to estimate serotype-specific invasiveness, i.e. the rate of invasive disease given carriage. This is useful for dynamic transmission modelling, as transmission is through carriage but a majority of serotype-specific pneumococcal data lies in active disease surveillance. This is also helpful to address whether serotype replacement reflects serotypes that are more invasive or whether serotypes in a specific location are equally more invasive than in other locations. Finally, the last aim of this thesis is to estimate the epidemiological and economic impact of increas- ing serotype coverage in PCVs using a dynamic transmission model. Together, the results highlight that though there are key parameter uncertainties that merit further exploration, divergence in serotype replacement and inconsistencies in invasiveness on a country-level may make a universal PCV suboptimal.Open Acces

    TOWARDS AN UNDERSTANDING OF EFFORTFUL FUNDRAISING EXPERIENCES: USING INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS IN FUNDRAISING RESEARCH

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    Physical-activity oriented community fundraising has experienced an exponential growth in popularity over the past 15 years. The aim of this study was to explore the value of effortful fundraising experiences, from the point of view of participants, and explore the impact that these experiences have on people’s lives. This study used an IPA approach to interview 23 individuals, recognising the role of participants as proxy (nonprofessional) fundraisers for charitable organisations, and the unique organisation donor dynamic that this creates. It also bought together relevant psychological theory related to physical activity fundraising experiences (through a narrative literature review) and used primary interview data to substantiate these. Effortful fundraising experiences are examined in detail to understand their significance to participants, and how such experiences influence their connection with a charity or cause. This was done with an idiographic focus at first, before examining convergences and divergences across the sample. This study found that effortful fundraising experiences can have a profound positive impact upon community fundraisers in both the short and the long term. Additionally, it found that these experiences can be opportunities for charitable organisations to create lasting meaningful relationships with participants, and foster mutually beneficial lifetime relationships with them. Further research is needed to test specific psychological theory in this context, including self-esteem theory, self determination theory, and the martyrdom effect (among others)

    Epilepsy Mortality: Leading Causes of Death, Co-morbidities, Cardiovascular Risk and Prevention

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    a reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected ... Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by ..

    Political Islam and grassroots activism in Turkey : a study of the pro-Islamist Virtue Party's grassroots activists and their affects on the electoral outcomes

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    This thesis presents an analysis of the spectacular rise of political Islam in Turkey. It has two aims: first to understand the underlying causes of the rise of the Welfare Party which -later became the Virtue Party- throughout the 1990s, and second to analyse how grassroots activism influenced this process. The thesis reviews the previous literature on the Islamic fundamentalist movements, political parties, political party systems and concentrates on the local party organisations and their effects on the party's electoral performance. It questions the categorisation of Islamic fundamentalism as an appropriate label for this movement. An exploration of such movements is particularly important in light of the event of 11`x' September. After exploring existing theoretical and case studies into political Islam and party activism, I present my qualitative case study. I have used ethnographic methodology and done participatory observations among grassroots activists in Ankara's two sub-districts covering 105 neighbourhoods. I examined the Turkish party system and the reasons for its collapse. It was observed that as a result of party fragmentation, electoral volatility and organisational decline and decline in the party identification among the citizens the Turkish party system has declined. However, the WP/VP profited from this trend enormously and emerged as the main beneficiary of this process. Empirical data is analysed in four chapters, dealing with the different aspects of the Virtue Party's local organisations and grassroots activists. They deal with change and continuity in the party, the patterns of participation, the routes and motives for becoming a party activist, the profile of party activists and the local party organisations. I explore what they do and how they do it. The analysis reveals that the categorisation of Islamic fundamentalism is misplaced and the rise of political Islam in Turkey cannot be explained as religious revivalism or the rise of Islamic fundamentalism. It is a political force that drives its strength from the urban poor which has been harshly affected by the IMF directed neoliberal economy policies. In conclusion, it is shown that the WP/VP's electoral chances were significantly improved by its very efficient and effective party organisations and highly committed grassroots activists

    Walking with the Earth: Intercultural Perspectives on Ethics of Ecological Caring

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    It is commonly believed that considering nature different from us, human beings (qua rational, cultural, religious and social actors), is detrimental to our engagement for the preservation of nature. An obvious example is animal rights, a deep concern for all living beings, including non-human living creatures, which is understandable only if we approach nature, without fearing it, as something which should remain outside of our true home. “Walking with the earth” aims at questioning any similar preconceptions in the wide sense, including allegoric-poetic contributions. We invited 14 authors from 4 continents to express all sorts of ways of saying why caring is so important, why togetherness, being-with each others, as a spiritual but also embodied ethics is important in a divided world

    Hunting Wildlife in the Tropics and Subtropics

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    The hunting of wild animals for their meat has been a crucial activity in the evolution of humans. It continues to be an essential source of food and a generator of income for millions of Indigenous and rural communities worldwide. Conservationists rightly fear that excessive hunting of many animal species will cause their demise, as has already happened throughout the Anthropocene. Many species of large mammals and birds have been decimated or annihilated due to overhunting by humans. If such pressures continue, many other species will meet the same fate. Equally, if the use of wildlife resources is to continue by those who depend on it, sustainable practices must be implemented. These communities need to remain or become custodians of the wildlife resources within their lands, for their own well-being as well as for biodiversity in general. This title is also available via Open Access on Cambridge Core

    Developing automated meta-research approaches in the preclinical Alzheimer's disease literature

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    Alzheimer’s disease is a devastating neurodegenerative disorder for which there is no cure. A crucial part of the drug development pipeline involves testing therapeutic interventions in animal disease models. However, promising findings in preclinical experiments have not translated into clinical trial success. Reproducibility has often been cited as a major issue affecting biomedical research, where experimental results in one laboratory cannot be replicated in another. By using meta-research (research on research) approaches such as systematic reviews, researchers aim to identify and summarise all available evidence relating to a specific research question. By conducting a meta-analysis, researchers can also combine the results from different experiments statistically to understand the overall effect of an intervention and to explore reasons for variations seen across different publications. Systematic reviews of the preclinical Alzheimer’s disease literature could inform decision making, encourage research improvement, and identify gaps in the literature to guide future research. However, due to the vast amount of potentially useful evidence from animal models of Alzheimer’s disease, it remains difficult to make sense of and utilise this data effectively. Systematic reviews are common practice within evidence based medicine, yet their application to preclinical research is often limited by the time and resources required. In this thesis, I develop, build-upon, and implement automated meta-research approaches to collect, curate, and evaluate the preclinical Alzheimer’s literature. I searched several biomedical databases to obtain all research relevant to Alzheimer’s disease. I developed a novel deduplication tool to automatically identify and remove duplicate publications identified across different databases with minimal human effort. I trained a crowd of reviewers to annotate a subset of the publications identified and used this data to train a machine learning algorithm to screen through the remaining publications for relevance. I developed text-mining tools to extract model, intervention, and treatment information from publications and I improved existing automated tools to extract reported measures to reduce the risk of bias. Using these tools, I created a categorised database of research in transgenic Alzheimer’s disease animal models and created a visual summary of this dataset on an interactive, openly accessible online platform. Using the techniques described, I also identified relevant publications within the categorised dataset to perform systematic reviews of two key outcomes of interest in transgenic Alzheimer’s disease models: (1) synaptic plasticity and transmission in hippocampal slices and (2) motor activity in the open field test. Over 400,000 publications were identified across biomedical research databases, with 230,203 unique publications. In a performance evaluation across different preclinical datasets, the automated deduplication tool I developed could identify over 97% of duplicate citations and a had an error rate similar to that of human performance. When evaluated on a test set of publications, the machine learning classifier trained to identify relevant research in transgenic models performed was highly sensitive (captured 96.5% of relevant publications) and excluded 87.8% of irrelevant publications. Tools to identify the model(s) and outcome measure(s) within the full-text of publications may reduce the burden on reviewers and were found to be more sensitive than searching only the title and abstract of citations. Automated tools to assess risk of bias reporting were highly sensitive and could have the potential to monitor research improvement over time. The final dataset of categorised Alzheimer’s disease research contained 22,375 publications which were then visualised in the interactive web application. Within the application, users can see how many publications report measures to reduce the risk of bias and how many have been classified as using each transgenic model, testing each intervention, and measuring each outcome. Users can also filter to obtain curated lists of relevant research, allowing them to perform systematic reviews at an accelerated pace with reduced effort required to search across databases, and a reduced number of publications to screen for relevance. Both systematic reviews and meta-analyses highlighted failures to report key methodological information within publications. Poor transparency of reporting limited the statistical power I had to understand the sources of between-study variation. However, some variables were found to explain a significant proportion of the heterogeneity. Transgenic animal model had a significant impact on results in both reviews. For certain open field test outcomes, wall colour of the open field arena and the reporting of measures to reduce the risk of bias were found to impact results. For in vitro electrophysiology experiments measuring synaptic plasticity, several electrophysiology parameters, including magnesium concentration of the recording solution, were found to explain a significant proportion of the heterogeneity. Automated meta-research approaches and curated web platforms summarising preclinical research could have the potential to accelerate the conduct of systematic reviews and maximise the potential of existing evidence to inform translation

    Strung pieces: on the aesthetics of television fiction series

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    As layered and long works, television fiction series have aesthetic properties that are built over time, bit by bit. This thesis develops a group of concepts that enable the study of these properties, It argues that a series is made of strung pieces, a system of related elements. The text begins by considering this sequential form within the fields of film and television. This opening chapter defines the object and methodology of research, arguing for a non-essentialist distinction between cinema and television and against the adequacy of textual and contextual analyses as approaches to the aesthetics of these shows. It proposes instead that these programmes should be described as televisual works that can be scrutinised through aesthetic analysis. The next chapters propose a sequence of interrelated concepts. The second chapter contends that series are composed of building blocks that can be either units into which series are divided or motifs that unify series and are dispersed across their pans. These blocks are patterned according to four kinds of relations or principles of composition. Repetition and variation are treated in tandem in the third chapter because of their close connection, given that variation emerges from established repetition. Exception and progression are also discussed together in the fourth chapter since they both require a long view of these serial works. The former, in order to be recognised as a deviation from the patterns of repetition and variation. The latter, In order to be understood in Its many dimensions as the series advances. Each of these concepts is further detailed with additional distinctions between types of units, motifs, repetitions, variations, and exceptions, using illustrative examples from numerous shows. In contrast, the section on progression uses a single series as case study, Carnivàle (2003-05), because this is the overarching principle that encompasses all the others. The conclusion considers the findings of the research and suggests avenues for their application
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