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SonOpt: Sonifying Bi-objective Population-Based Optimization Algorithms
No full textWe propose SonOpt, the first (open source) data sonification application for monitoring the progress of bi-objective populationbased optimization algorithms during search, to facilitate algorithm understanding. SonOpt provides insights into convergence/stagnation of search, the evolution of the approximation set shape, location of recurring points in the approximation set, and population diversity. The benefits of data sonification have been shown for various non-optimization related monitoring tasks. However, very few attempts have been made in the context of optimization and their focus has been exclusively on single-objective problems. In comparison, SonOpt is designed for biobjective optimization problems, relies on objective function values ofnon-dominated solutions only, and is designed with the user (listener) in mind; avoiding convolution of multiple sounds and prioritising ease of familiarizing with the system. This is achieved using two sonification paths relying on the concepts of wavetable and additive synthesis.This paper motivates and describes the architecture of SonOpt, and then validates SonOpt for two popular multi-objective optimization algorithms (NSGA-II and MOEA/D). Experience SonOpt yourself viahttps://github.com/tasos-a/SonOpt-1.0.Keywords: sonification · optimization · algorithmic behaviour · metaheuristics · evolutionary computation · process monitoring · SonOpt
Autistic Girls and Emotionally Based School Avoidance: Supportive factors for successful re-engagement in mainstream high school
No full textSchool can be challenging for autistic girls who are at risk of internalised anxiety which can ultimately lead to school avoidance. Low attendance is acknowledged as negatively impacting on educational attainment and exacerbating mental health difficulties. Semi-structured interviews were conducted with three autistic girls aged 13-15 years from different high schools, their parent(s) and key adult. Thematic analysis identified the first phase of re-engagement is developing a trusting student-key adult relationship. This provides the foundation for social and emotional intervention. Challenges were also acknowledged and possible improvements reflected upon. These results will aid educators and researchers aiming to support the successful inclusion of autistic girls at risk of experiencing emotionally based school avoidance in mainstream high schools
New Reaction Pathways by Integrating Chemo- and Biocatalysis
No full textThe combination of chemo- and biocatalysis in one-pot (integrated catalysis) is a powerful approach to develop new routes towards important products under mild and environmentally benign reaction conditions. Integrated catalysis can improve overall synthetic efficiency and, due to the complementary nature of chemo- and biocatalysts, transformations can be performed, which would be otherwise challenging using a single catalyst. In this review, we highlight recent trends for the combination of enzymes with chemocatalysts. Transition-metal catalysis, organocatalysis, and photoredox catalysis have been combined with different biocatalysts and discussed accordingly. We highlight further how integrated catalysis does not only deliver benign substitutes for known transformations but moreover enables transformations which would be otherwise impossible
Cluster Model Study into the Catalytic Mechanism of α-Ketoglutarate Biodegradation by the Ethylene-Forming-Enzyme Reveals Structural Differences with Nonheme Iron Hydroxylases
No full textEthylene is an important signaling molecule in plants that triggers the growth of leaves, flowers and fruits. One of the enzymes involved in the biosynthesis of ethylene is the ethylene-forming enzyme (EFE), which is an usual nonheme iron enzyme that biodegrades α-ketoglutarate to three CO2 molecules and ethylene. As the detailed mechanism of EFE and its biosynthesis of ethylene remains controversial and particularly the function of the co-substrate L-arginine, we decided to pursue a density functional theory study on possible pathways of the enzyme leading to its ethylene biosyn-thesis and test many possible pathways and mechanisms. A large active site cluster model of 322 atoms was created that contains all features of the first- and second-coordination sphere of the active site and substrate (α-ketoglutarate) binding pockets. The calculations identify a persuccinate intermediate that triggers a bifurcation pathway in the enzyme and either reacts with a molecule of CO2 to form carbonate or forms a high-valent iron(IV)-oxo species through heterolytic dioxygen bond cleavage. Our studies show that both bifurcation pathways converge to the same intermediate again and can lead to ethylene products, although the two pathways have different kinetics. Interestingly, our studies also show that the iron(IV)-oxo itself can form carbonate and ethylene but through much higher barriers. As a matter of fact, these barriers are higher in energy than typical aliphatic hydroxylation barriers and may not be competitive with arginine hydroxylation. Inclusion of L-arginine co-substrate into the model leads to minor changes in the structure and fold and its charge and dipole moment does not seem to affect the first stage of the catalytic cycle. Moreover, key activation barriers appear little affected by the inclusion of L-arginine into the model. We, therefore, believe that L-arginine’s role is to lock α-ketoglutarate and its products into a tight binding pocket to enable its degradation and to prevent early release of CO2. Our studies show that due to distinct differences in α-ketoglutarate positioning between different arginine activating nonheme iron dioxygenases in the co-substrate binding pocket and its tighter binding in EFE, we predict that the release of CO2 is prevented in the first stage of the oxygen activation mechanism. This enables attack of CO2 on a persuccinate complex to form carbonate products leading to ethylene formation. The work gives suggestions on the engineering of EFE into a hydroxylase or improve the ethylene biosynthesis
Impact and control of fouling in radioactive environments.
No full textFouling and scaling of equipment in the nuclear industry is a significant and challenging problem that effects multiple areas across the entire nuclear fuel cycle. Consequences such as the blockage of fluid flow, accumulation of radionuclides, reduction of heat-transfer energy and enhancement of corrosion, all can have detrimental effects on safety and performance as well as incurring substantial damage and maintenance costs amounting to billions of pounds a year. This review focuses on pipelines and understanding the mechanisms of formation and radionuclide incorporation of inorganic and biological fouling, and microbially influenced corrosion (MIC) mechanisms, as well as exploring prevalent examples in the nuclear industry and parallels in the oil and gas industries. The review will also cover advancements in fouling and scale mitigation and treatment strategies, which are imperative to reduce economic loses and avoid safety hazards in nuclear as well as many other industries
Biographical accounts of the impact of fatigue in young people with sickle cell disease
No full textChildren and young people (CYP) with sickle cell disease (SCD) are a 'missing voice' in the debate on biography and sociology of chronic illness, meaning we know little about the social consequences of the illness for CYP. This paper examines the meaning of fatigue (a common symptom) for adolescents with SCD. Analysing 24 in-depth interviews with adolescents aged 12-17 years in Ghana, we draw on the distinction proposed by Bury (1988) between 'meanings as significance' and 'meanings as consequence' to examine biographical aspects of fatigue. We argue that concepts of 'biographical disruption' and 'normal illness' do not easily accommodate the experience of CYP with congenital chronic illnesses like SCD, as their sense of (un)disruption and normality/continuity is contextualised relative to normative expectations about what it is to be a young person. At biographical transition points, illness/symptoms present from birth may evolve, shift and become experienced as 'new', 'different', or 'non-normal'. They may become restrictive rather than continuous or disruptive. These experiences are influenced primarily by normative biographical expectations and the pursuit of identity affirmations. We propose that biographical restriction, biographical enactment, biographical abandonment and biographical reframing are more relevant concepts for understanding the experiences of CYP living with SCD
Impact of myocardial fibrosis on cardiovascular structure, function and functional status in heart failure with preserved ejection fraction
No full textMyocardial fibrosis, measured using cardiovascular magnetic resonance extracellular volume (ECV), is associated with adverse outcome in heart failure with preserved ejection fraction but the mechanisms by which myocardial fibrosis exerts this deleterious effect are unclear. We performed mediation analyses of data from the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial to determine whether myocardial fibrotic regression causes changes in cardiovascular function and functional status following antifibrotic therapy. Regression of myocardial fibrosis correlated with improvements in 6-minute walk test and KCCQ clinical summary score. The only outcome variable that demonstrated a treatment effect was an increase in left ventricular ejection fraction (LVEF). The estimated average causal mediation effects of myocardial ECV, absolute myocardial extracellular matrix volume and absolute myocardial cellular volume on LVEF were 6.1%, 21.5%, and 13.7% respectively, none of which were significant and therefore not mediated by myocardial fibrosis. (PIROUETTE; NCT02932566)
Denosumab and risk of community-acquired pneumonia: A population-based cohort study
No full textContext: Recent meta-analyses of randomized controlled trials raised concerns that denosumab might increase the risk of infection. However, data of denosumab on the risk of community-acquired pneumonia is sparse. Objective: To examine the risk of community-acquired pneumonia in subjects receiving denosumab compared to those receiving alendronate.Design: We conducted a propensity score-matched cohort study with a UK primary care database (IQVIA Medical Research Database). We examined the relation of denosumab to community-acquired pneumonia using a Cox proportional hazard model.Participants: The study subjects were osteoporotic patients >45 years who were initiators of denosumab or alendronate from August 1, 2010, to September 17, 2020.Outcome Measures: Community-acquired pneumonia.Results: Patients treated with denosumab (n=933) were compared with those treated with alendronate (n=4,652). In the matched population, the mean (SD) age was 77 (11) years, 89% were women, and about half of the study population had a history of major osteoporotic fracture. Over five years follow-up, the incidence of community-acquired pneumonia per 1000 person-years was 72.0 (95% confidence interval [CI] 60.1, 85.7) in the denosumab group and 75.1 (95%CI 69.4, 81.2) in the alendronate group. The hazard of community-acquired pneumonia was similar between denosumab and alendronate users (hazard ratio [HR] 0.96; 95% 0.79, 1.16). The results remain consistent in a series of sensitivity analyses, with HR ranging from 0.82 (95% CI 0.65, 1.04) to 0.99 (95% CI 0.81, 1.21).Conclusion: Denosumab does not significantly increase the susceptibility of community-acquired pneumonia and could possibly be safely used for the management of osteoporosis. <br/