Artificial evolution with Binary Decision Diagrams: a study in evolvability in neutral spaces

This thesis develops a new approach to evolving Binary Decision Diagrams, and uses it to study evolvability issues. For reasons that are not yet fully understood, current approaches to artificial evolution fail to exhibit the evolvability so readily exhibited in nature. To be able to apply evolvability to artificial evolution the field must first understand and characterise it; this will then lead to systems which are much more capable than they are currently. An experimental approach is taken. Carefully crafted, controlled experiments elucidate the mechanisms and properties that facilitate evolvability, focusing on the roles and interplay between neutrality, modularity, gradualism, robustness and diversity. Evolvability is found to emerge under gradual evolution as a biased distribution of functionality within the genotype-phenotype map, which serves to direct phenotypic variation. Neutrality facilitates fitness-conserving exploration, completely alleviating local optima. Population diversity, in conjunction with neutrality, is shown to facilitate the evolution of evolvability. The search is robust, scalable, and insensitive to the absence of initial diversity. The thesis concludes that gradual evolution in a search space that is free of local optima by way of neutrality can be a viable alternative to problematic evolution on multi-modal landscapes

Chronic type B dissecting aortoiliac aneurysm repair complicated by congenital pelvic kidney

Although the association between abdominal aortic aneurysm and pelvic kidney is rare, previous reports have described various methods of repair with successful preservation of pelvic kidney function. We describe a unique case complicated by aortic dissection. Successful intra-operative perfusion of the kidney was maintained via a temporary axillorenal shunt

How can clinical research improve European health outcomes in cancer?

We review the mechanisms by which clinical cancer research can improve health outcomes and argue that this should be central to the development of policy. Recent series of major international studies have analysed large, often nationwide, datasets for cancer patient outcomes and participation in clinical research. They have evaluated and quantified the impact of new evidence generated by randomised controlled trials on cancer survival. They show a strong and probably causal relationship between the participation in clinical research in hospitals and the outcomes for patients with the disease under study in those hospitals. Also, institutions that are active in clinical trials appear to take up well evidenced innovations more rapidly than those which are not so engaged. Further work is necessary to confirm and examine the generalisability of these findings but we argue that all of these mechanisms are likely to lead to improved outcomes for patients as a consequence of the conduct of clinical research. The size of the benefit appears to be substantial and an active programme to promote clinical research across cancer care systems should be a part of National Cancer Plans and Cancer Control Strategies

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

Implementation of child-centred outcome measures in routine paediatric healthcare practice: a systematic review

Background: Person-centred outcome measures (PCOMs) are commonly used in routine adult healthcare to measure and improve outcomes, but less attention has been paid to PCOMs in children’s services. The aim of this systematic review is to identify and synthesise existing evidence of the determinants, strategies, and mechanisms that influence the implementation of PCOMs into paediatric healthcare practice. Methods: The review was conducted and reported in accordance with PRISMA guidelines. Databased searched included CINAHL, Embase, Medline, and PsycInfo. Google scholar was also searched for grey literature on 25th March 2022. Studies were included if the setting was a children’s healthcare service, investigating the implementation or use of an outcome measure or screening tool in healthcare practice, and reported outcomes relating to use of a measure. Data were tabulated and thematically analysed through deductive coding to the constructs of the adapted-Consolidated Framework for Implementation Research (CFIR). Results were presented as a narrative synthesis, and a logic model developed. Results: We retained 69 studies, conducted across primary (n = 14), secondary (n = 13), tertiary (n = 37), and community (n = 8) healthcare settings, including both child self-report (n = 46) and parent-proxy (n = 47) measures. The most frequently reported barriers to measure implementation included staff lack of knowledge about how the measure may improve care and outcomes; the complexity of using and implementing the measure; and a lack of resources to support implementation and its continued use including funding and staff. The most frequently reported facilitators of implementation and continued use include educating and training staff and families on: how to implement and use the measure; the advantages of using PCOMs over current practice; and the benefit their use has on patient care and outcomes. The resulting logic model presents the mechanisms through which strategies can reduce the barriers to implementation and support the use of PCOMs in practice. Conclusions: These findings can be used to support the development of context-specific implementation plans through a combination of existing strategies. This will enable the implementation of PCOMs into routine paediatric healthcare practice to empower settings to better identify and improve child-centred outcomes. Trial registration: Prospero CRD 42022330013

What Stimulates Researchers to Make Their Research Usable? Towards an Openness Approach

Ambiguity surrounding the effect of external engagement on academic research has raised questions about what motivates researchers to collaborate with third parties. We argue that what matters for society is research that can be absorbed by users. We define openness as a willingness by researchers to make research more usable by external partners by responding to external influences in their own research practices. We ask what kinds of characteristics define those researchers who are more open to creating usable knowledge. Our empirical study analyses a sample of 1583 researchers working at the Spanish Council for Scientific Research (CSIC). Results demonstrate that it is personal factors (academic identity and past experience) that determine which researchers have open behaviours. The paper concludes that policies to encourage external engagement should focus on experiences which legitimate and validate knowledge produced through user encounters, both at the academic formation career stage as well as through providing ongoing opportunities to engage with third parties.The data used for this study comes from the IMPACTO project funded by the Spanish Council for Scientific Research - CSIC (Ref. 200410E639). The work also benefited from a mobility grant awarded by Eu-Spri Forum to Julia Olmos Penuela & Paul Benneworth for her visiting research to the Center of Higher Education Policy Studies. Finally, Julia Olmos Penuela also benefited from a post-doctoral grant funded by the Generalitat Valenciana (APOSTD-2014-A-006).Olmos-Peñuela, J.; Benneworth, P.; Castro-Martínez, E. (2015). What Stimulates Researchers to Make Their Research Usable? Towards an Openness Approach. 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Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant