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This thesis is about the perceptual nature of aesthetic experience and the importance of nature as a paradigmatic object of aesthetic perception and aesthetic experience more broadly conceived. For this reason, it merits serious attention by philosophers working in aesthetics, as has been argued since Ronald Hepburn’s seminal essay “Contemporary Aesthetics and the Neglect of Natural Beauty”. If aesthetic experience is anything, it is at least perceptual. It is a mode of perceptual experience that is the result of having been attentive to and having discriminated between, the aesthetic and non-aesthetic, and invites room for reflection on, and connections to be made with, cognitive and emotive processes. Rooting the aesthetic in perception allows us to recognize and understand that it has an impact on our daily activities, rather than being restricted either to a particular kind of object, to the knowledge we might have about it, or to intense, rarefied aesthetic experience. If an object is to be an aesthetic object it need not be an artwork, indeed, one might even argue that nature is more interesting an aesthetic object from the perspective that it is indeterminate, not the result of human intentionality, and from an existential point of view, one that acknowledges our dependence on it. In the course of the argument, I thus resist the idea that the aesthetic experience of art is necessarily prior to the aesthetic experience of nature. The perceptual account put forward is based on a realist account of aesthetic properties that considers aesthetic properties to be perceptual properties and that considers aesthetic experience to be perceptually rich. I link it to the idea of ‘whole formalism’, a perceptual, aesthetic account that is nestled in the wider thought that aesthetic perception relates, although not causally, to other features of experience, such as emotion, and knowledge. Perceptual, aesthetic experience is thus not reduced to an austere account of aesthetic formalism. The thesis begins by analysing historical accounts of aesthetic perception, beginning with Plato, Aristotle and Aquinas. It builds on this analysis by reinterpreting crucial concepts to the discipline of aesthetics, such as disinterest and formalism that originated in the eighteenth century and are relevant to the idea of aesthetic perception. It then brings the idea of aesthetic perception up to date by addressing the current debate about cognitivism and non-cognitivism about aesthetic experience where nature is concerned. By tracing the idea of aesthetic perception historically, I will have also shown the role of nature as a paradigm of aesthetic experience through history and that nature is a repository for rich aesthetic experience and for rich experiential engagement with it.

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 588,452 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies. Multi-ancestry genome-wide association analyses and systematic variant-to-gene mapping strategies implicate new genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.

High-quality implementation research is fundamental to increasing the uptake of evidence-based interventions in healthcare and ultimately improving healthcare delivery and outcomes. However, the development of high-quality implementation research proposals and the identification of the 'best' implementation research proposals to fund are hampered by the lack of criteria for their appraisal. This study describes the development and evaluation of the Implementation Research Proposal Appraisal Criteria (ImpResPAC), a comprehensive tool developed to help research teams identify strengths and weaknesses of their implementation research proposals and provide grant reviews with clear criteria for appraising the conceptual and methodological quality of implementation research proposals. A two-stage sequential mixed-methods design, including content development (stage 1) and a two-round modified e-Delphi (stage 2a & 2b), was employed. Stage 1: Informed by the structure and content of the Implementation Science Research Development (ImpRes) tool and supplementary guide, and a previous study in which five of the ten ImpRes domains were operationalised to develop five ImpResPAC domains, the ImpResPAC development team developed the initial content of ImpResPAC. Purposive and snowball sampling was used to recruit an Expert Advisory Panel (EAP), of individuals that have made a significant contribution to the conceptual and methodological advancement of implementation science. Stage 2a: The EAP provided feedback on ImpResPAC. Based on the feedback, the ImpResPAC development team made extensive revisions to ImpResPAC. Stage 2b: The refined ImpResPAC was shared with the EAP for further feedback and evaluation. Sixty-eight international experts formed the EAP. ImpResPAC includes 71 domain items, each indicative of high-quality implementation research. The domain items are organised over 10 domains each representing a core element of implementation research. Based on feedback, user instructions were refined, and a glossary of terms used in ImpResPAC was developed. ImpResPAC is a comprehensive and transparent quantitative tool to appraise the conceptual and methodological quality of implementation research proposals in healthcare. Application of ImpResPAC has several potential and immediate benefits; it will support research teams identify strengths and weaknesses of their implementation research proposals and in turn develop high-quality proposals, enable grant reviewers to identify the 'best' implementation research proposals to fund, and provide a comprehensive tool to be used by educators to appraise implementation research proposals submitted as part of implementation science teaching and training initiatives.

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 cases and 64,762 controls of European descent, followed by genotyping of top association signals in 60,738 additional individuals. This genomic analysis identified 13 novel loci harboring one or more SNPs that were associated with CAD at P<5×10−8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 novel loci displayed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6 to 17 percent increase in the risk of CAD per allele. Notably, only three of the novel loci displayed significant association with traditional CAD risk factors, while the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the novel CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.