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    Structure of mushy layers grown from perfectly and imperfectly conducting boundaries. Part 1. Diffusive solidification

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    We model transient mushy-layer growth for a binary alloy solidifying from a cooled boundary, characterising the impact of liquid composition and thermal growth conditions on the mush porosity and growth rate. We consider cooling from a perfectly conducting isothermal boundary, and from an imperfectly conducting boundary governed by a linearised thermal boundary condition. For an isothermal boundary we characterise different growth regimes depending on a concentration ratio, which can also be viewed as characterising the ratio of composition-dependent freezing point depression versus the temperature difference across the mushy layer. Large concentration ratio leads to high porosity throughout the mushy layer and an asymptotically simplified model for growth with an effective thermal diffusivity accounting for latent heat release from internal solidification. Low concentration ratio leads to low porosity throughout most of the mushy layer, except for a high-porosity boundary layer localised near the mush–liquid interface. We identify scalings for the boundary-layer thickness and mush growth rate. An imperfectly conducting boundary leads to an initial lag in the onset of solidification, followed by an adjustment period, before asymptoting to the perfectly conducting state at large time. We develop asymptotic solutions for large concentration ratio and large effective heat capacity, and characterise the mush structure, growth rate and transition times between the regimes. For low concentration ratio the high porosity zone spans the full mush depth at early times, before localising near the mush–liquid interface at later times. Such variation of porosity has important implications for the properties and biological habitability of mushy sea ice

    GPU accelerated image quality assessment-based software for transient detection

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    Fast imaging localises celestial transients using source finders in the image domain. The need for high computational throughput in this process is driven by nextgeneration telescopes such as Square Kilometre Array (SKA), which, upon completion, will be the world’s largest aperture synthesis radio telescope. It will collect data at unprecedented velocity and volume. Due to the vast amounts of data the SKA will produce, current source finders based on source extraction may be inefficient in a wide-field search. In this paper, we focus on the software development of GPUaccelerated transient finders based on Image Quality Assessment (IQA) methods — Low-Information Similarity Index (LISI) and augmented LISI (augLISI). We accelerate the algorithms using GPUs, achieving kernel time of approximately 0.1 milliseconds for transient finding in 2048 × 2048 images

    Identifying antifungal resistance mechanisms and modes of action using SAturated Transposon Analysis in Yeast (SATAY)

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    Fungal pathogens are a serious burden for public health and global food security. This problem is exacerbated by the rapid emergence of resistance to our limited armamentarium of antifungal compounds. The future control of fungal diseases therefore depends on the discovery of antifungals with novel modes of action and the development of robust resistance management strategies. These strategies require a comprehensive understanding of the molecular mechanisms governing antifungal resistance, yet our knowledge is incomplete. Recently, a powerful transposon sequencing method was developed in Saccharomyces cerevisiae, called SAturated Transposon Analysis in Yeast (SATAY). SATAY couples saturated transposon mutagenesis to next-generation sequencing, allowing the genome-wide identification of growth-affecting loci in a straightforward and time-efficient manner. Importantly, SATAY can identify loss- and gain-of-function mutations conferring antifungal resistance, as well as the direct targets of antifungal compounds. This thesis applies SATAY to uncover novel antifungal resistance mechanisms and to examine the modes of action of nine antifungal compounds. These screens reveal antifungal drug targets, transporters responsible for drug uptake or efflux, as well as metabolic, signalling and trafficking pathways affecting antifungal susceptibility. The most novel and interesting findings in these screens are characterised further. This includes the discovery of Hol1 as the transporter that concentrates the potent antifungal ATI-2307 within yeast, a finding that unveils a straightforward evolutionary path to ATI-2307 resistance with minimal fitness cost. SATAY is also performed in drug-sensitive strains to examine antifungals that lack activity against conventional laboratory strains. This approach is utilised to test a previously proposed model for the mode of action of Fludioxonil, and identifies cell wall mannosylphosphate as the target for the natural antifungal Chitosan. Together, this thesis improves our understanding of several antifungal modes of action and unveils a diverse array of resistance mechanisms, supporting efforts to address the increasing threats posed by multidrug-resistant fungal pathogens

    Impact of interspecific competition on African wild dogs (Lycaon pictus) in an ecosystem with artificial perennial water provision

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    Interspecific competition with large predators affects African wild dogs through food resource competition, exclusion from prey rich areas, kleptoparasitism, injury, mortality, den site selection, and human landscape exposure. Waterhole distance and density can work as surrogates on prey aggregation and abundance, which in turn these resources attract large dominant predators. Subordinate smaller predators, such as African wild dogs, have to balance the trade-off between resource acquisition and the risk of encountering large predators. My aim is to determine how African wild dogs cope with the competition with larger dominant predators (mainly lions and spotted hyaenas - hyaenas) in a semi-arid ecosystem with artificial water provision: Hwange National Park (HNP), Zimbabwe. In HNP, during the dry season the only water available for animals is mainly found in artificial waterholes, which makes this area ideal to perform this research. First, I evaluated the food resource competition of African wild dogs with competing predators (cheetahs, leopards, lions and hyaenas) in different seasons and across areas with different waterhole densities, using predators scats to analyse diet composition, diet comparisons, diet overlap, niche breadth, and prey preference (Chapter 2). Secondly, I assessed the level of kleptoparasitism risk for African wild dogs from lions and hyaenas in areas with different waterhole densities and at different distances from waterholes (0 and 5 km away), using playback experiments simulating African wild dog kills and analysing the data with hurdle models (Chapter 3). Thirdly, I evaluated if African wild dogs avoid large competing predators (leopards, lions and hyaenas) reactively or proactively in space and time at different spatial and temporal scales, using camera trap data to perform generalized linear mixed models, activity pattern overlap and time-to-event analyses (Chapter 4). Finally, I discussed water management strategies to help decrease the level of interspecific competition on African wild dogs and assist in their conservation (Chapter 5). My main results show that: a) prey conservation mainly in low waterhole density areas is crucial to decrease food resource competition between African wild dogs with large predators (Chapter 2); b) areas with too high waterhole densities increased the kleptoparasitism risk on African wild dogs and hence the risk of agonistic encounters with dominant predators through an increase on the number of dominant predators arriving at playback locations (Chapter 3); c) African wild dogs preferred temporal partitioning over spatial partitioning to avoid large predators, and African wild dogs were able to co-occur in areas (rich in prey) with high aggregation and density of dominant predators as long as there were enough permanent waterhole densities (at least ~0.01 waterholes per km2) and not too high hyaena densities (above ~14 hyaenas/100km2) (Chapter 4). Specifically to decrease the interspecific competition intensity of African wild dogs with larger predators, it is important that there are areas with enough permanent waterholes (at least ~0.01 waterholes per km2) during the late dry season, but to also limit the number of artificial waterholes created in high waterhole density areas (above ~0.03 waterholes per km2) (Chapter 5). A heterogeneous water management system is recommended. This study is relevant to the overarching conservation work in areas with water provisioning as a conservation management tool

    The political-economic risks of AI

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    The political and economic risks of artificial intelligence have been over shadowed by fears of malicious superintelligence and killer robots. Due to AI’s distinctive features—automation of cognitive tasks, global scalability, general-purpose technology, and importance to national security—its impact could be unlike earlier rounds of automation. It is possible that AI creates a superabundant world with unprecedented human freedom. In this essay, however, I will explore a tail risk in which human-level artificial general intelligence (AGI) radically concentrates the global economy, breaks democratic and egalitarian institutions, and tears the social fabric, collapsing human productivity. The closest precedent would be the cultural devastation of indigenous societies by colonialism. I will describe how this process might unfold and propose measures to ensure AI has widespread benefits. Competition policy emerges as a critical tool, as do adaptive changes to political institutions. Without appropriate measures, there may be no AI-driven growth take-off and the inequality that emerges would dwarf anything experienced to date

    Desire and disinterest in Dusklands

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    Disinterest is one of the most distrusted of all the terms which pass down to us from post-Kantian aesthetic theory, because it is often taken to imply an ideologically suspect transcendence of the desiring embodied subject. Yet the need to which it points persists, as is evident from Coetzee’s discussion of ‘free play’ in his essay ‘Erasmus: Madness and Rivalry’ (1992), where a certain conception of aesthetic disinterest (a sought-for ‘evasive (non)position inside/outside the play’) is seen as being related to, rather than disavowing, the desire of writer and readers alike. This paper traces the prehistory of these important remarks back to the period of Dusklands, and to Herbert Marcuse’s attempt to conjoin Freudian psychoanalysis with post-Kantian aesthetic theory. I will argue that Marcuse was an influence Coetzee needed both to assimilate and to challenge

    Asymmetric projection of introspection reveals a behavioural and neural mechanism for interindividual social coordination

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    When we collaborate with others to tackle novel problems, we anticipate how they will perform their part of the task to coordinate behavior effectively. We might estimate how well someone else will perform by extrapolating from estimates of how well we ourselves would perform. This account predicts that our metacognitive model should make accurate predictions when projected onto people as good as, or worse than, us but not on those whose abilities exceed our own. We demonstrate just such a pattern and that it leads to worse coordination when working with people more skilled than ourselves. Metacognitive projection is associated with a specific activity pattern in anterior lateral prefrontal cortex (alPFC47). Manipulation of alPFC47 activity altered metacognitive projection and impaired interpersonal social coordination. By contrast, monitoring of other individuals’ observable performance and outcomes is associated with a distinct pattern of activity in the posterior temporal parietal junction (TPJp)

    Interventions for quitting vaping

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    Rationale There is limited guidance on the best ways to stop using nicotine‐containing vapes (otherwise known as e‐cigarettes) and ensure long‐term abstinence, whilst minimising the risk of tobacco smoking and other unintended consequences. Treatments could include pharmacological interventions, behavioural interventions, or both. Objectives To conduct a living systematic review assessing the benefits and harms of interventions to help people stop vaping compared to each other or to placebo or no intervention. To also assess how these interventions affect the use of combustible tobacco, and whether the effects vary based on participant characteristics. Search methods We searched the following databases from 1 January 2004 to 24 April 2024: CENTRAL; MEDLINE; Embase; PsycINFO; ClinicalTrials.gov (through CENTRAL); World Health Organization International Clinical Trials Registry Platform (through CENTRAL). We also searched the references of eligible studies and abstracts from the Society for Research on Nicotine and Tobacco 2024 conference, and contacted study authors. Eligibility criteria Randomised controlled trials (RCTs) recruiting people of any age using nicotine‐containing vapes, regardless of tobacco smoking status. Studies had to test an intervention designed to support people to quit vaping, and plan to measure at least one of our outcomes. Outcomes Critical outcomes: vaping cessation; change in combustible tobacco use at six months or longer; number of participants reporting serious adverse events (SAEs) at one week or longer. Risk of bias We used the Cochrane RoB 1 tool to assess bias in the included studies. Synthesis methods We followed standard Cochrane methods for screening and data extraction. We grouped studies by comparisons and outcomes reported, and calculated individual study and pooled effects, as appropriate. We used random‐effects Mantel‐Haenszel methods to calculate risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. We used random‐effects inverse variance methods to calculate mean differences and 95% CI for continuous outcomes. We assessed the certainty of the evidence using the GRADE approach. Included studies Nine RCTs, representing 5209 participants motivated to stop using nicotine‐containing vapes at baseline, are included. In six studies, participants were abstinent from smoking tobacco cigarettes at baseline, although most studies included some participants who had previously smoked. Eight studies included participants aged 18 or older, three included only young adults (18 to 24 years), and one included 13‐ to 17‐year‐olds only. We judged three studies at low risk, three at high risk, and three at unclear risk of bias. Synthesis of results Pharmacological interventions for quitting nicotine vaping Studies assessed combination nicotine replacement therapy (NRT), cytisine, and varenicline as pharmacological interventions for quitting vaping in comparison to placebo or no/minimal support (control). The point estimate for combination NRT indicated possible benefit, but the CI incorporated the possibility of no benefit and a potential benefit of control (very low‐certainty evidence due to imprecision and risk of bias; RR 2.57, 95% CI 0.29 to 22.93; 1 study, 16 participants). The one study investigating cytisine did not report vaping cessation rates at six months or longer. Varenicline increased vaping cessation rates at six months, but the evidence was low certainty due to imprecision (RR 2.00, 95% CI 1.09 to 3.68; 1 study, 140 participants). Zero participants reported SAEs in the studies of combination NRT versus no/minimal support (1 study, 508 participants; low‐certainty evidence due to imprecision) and cytisine versus placebo (1 study, 159 participants; low‐certainty evidence due to imprecision). Three studies investigating varenicline measured the number of participants reporting SAEs. However, only one study reported an SAE (in the intervention arm); therefore, the effect estimate was calculated based on that single study (RR 2.60, 95% CI 0.11 to 62.16; 95 participants; low‐certainty evidence due to imprecision). Behavioural interventions for quitting nicotine vaping Studies assessed reducing nicotine concentration and vaping behaviour (1 study) and text message‐based interventions (3 studies) as behavioural interventions for stopping vaping in comparison to no/minimal support (control). In one study, the point estimate suggested nicotine/vaping reduction increased vaping cessation compared to minimal support at six‐month follow‐up, but the CI incorporated the possibility of no intervention effect and higher cessation rates in the control arm (RR 3.38, 95% CI 0.43 to 26.30; 17 participants; very low‐certainty due to imprecision and risk of bias). There was low‐certainty evidence (downgraded two levels due to indirectness) that text message‐based interventions may have increased vaping cessation rates compared to control in 13‐ to 24‐year‐olds (RR 1.32, 95% CI 1.19 to 1.47; I2 = 0%; 2 studies, 4091 participants). The one study investigating nicotine/vaping behaviour reduction did not report on SAEs. One of the studies investigating text message‐based interventions did report on SAEs; however, zero events were reported in both study arms (508 participants; low‐certainty evidence due to imprecision). No studies reported change in combustible tobacco smoking at six‐month follow‐up or longer. Authors' conclusions There is low‐certainty evidence that text message‐based interventions designed to help people stop nicotine vaping may help more youth and young adults to successfully stop than no/minimal support, and low‐certainty evidence that varenicline may also help people quit vaping. Data exploring the effectiveness of combination NRT, cytisine, and nicotine/vaping behaviour reduction are inconclusive due to risk of bias and imprecision. Most studies that measured SAEs reported none; however, more data are needed to draw clear conclusions. Of note, data from studies investigating these interventions for quitting smoking have not demonstrated serious concerns about SAEs. No studies assessed the change in combustible tobacco smoking, including relapse to or uptake of tobacco smoking, at six‐month follow‐up or longer. It is important that future studies measure this so the complete risk profile of relevant interventions can be considered. We identified 20 ongoing RCTs. Their incorporation into the evidence base and the continued identification of new studies is imperative to inform clinical and policy guidance on the best ways to stop vaping. Therefore, we will continue to update this review as a living systematic review by running searches monthly and updating the review when relevant new evidence that will strengthen or change our conclusions emerges. Funding Cancer Research UK (PRCPJT‐Nov22/100012). National Institute of Health Research (NIHR206123) Registration Protocol available via DOI: 10.1002/14651858.CD016058

    Sexual violence at higher education institutions: prevalence, nature, and opportunities for prevention

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    Background: Sexual violence (SV) in higher education institutions (HEIs) threatens student safety, health, well-being, and educational outcomes. While there is an abundance of evidence from the United States on SV in these settings, there is a need to understand how this issue manifests itself both globally and in the United Kingdom (UK) context. Universities UK has specifically called for UK HEIs to collect adequate data on SV at HEIs to inform current and future prevention and response initiatives. Objectives: The first objective was to gather and synthesise the available evidence on the prevalence of SV at HEIs globally. The second objective was to explore the prevalence, nature, and culture of SV among students at a UK HEI by implementing a pilot survey at the University of Oxford. Method: First, I conducted a systematic review of SV prevalence studies at HEIs and meta-analysed the prevalence of SV disaggregated by gender, type of SV, and world region. Second, in collaboration with stakeholders across the University of Oxford, I developed a cross-sectional survey (the OUR SPACE survey) to measure the prevalence, nature, and context of SV at the University of Oxford. This survey was administered to all full-time registered students in 2021. Using the OUR SPACE data, I estimated the past-year prevalence of SV at the University of Oxford disaggregated by type of SV, gender identity, sexual orientation, and ethnicity. I also used the OUR SPACE data to analyse respondent attitudes about SV, respondent bystander behaviours, and the relationship between the two variables. Results: Through the systematic review with meta-analyses of prevalence studies I found that 11% of students experienced SV (which included attempted and completed forced sexual touching, coercive sex, and attempted or completed rape) while attending an HEI. Among the students participating in the OUR SPACE survey, I found 20% experienced at least one act of SV and 53% experienced at least one act of sexual harassment (which included unwanted acts of a sexual nature that did not involve physical touch, such as crude sexual or sexist remarks and stalking). Across both studies I found that women and transgender and gender-diverse people experienced the largest burden of all types of SV. Using the OUR SPACE data, I also found that gendered differences persisted across willingness to engage in bystander behaviour to prevent or respond to SV, with men being less likely to engage in bystander behaviour to prevent SV and more likely to endorse attitudes that place the blame of SV on victims or survivors. I further found that respondents with attitudes of SV that placed the blame for SV on survivors were less willing to engage in bystander behaviour to prevent or respond to SV. Conclusion: I contributed to existing evidence on the prevalence, nature, and culture of SV in HEIs. In doing so I experienced barriers such as limitations to the existing evidence base on prevalence studies (e.g., nonresponse bias and measurement issues) and limitations to the validity and generalisability of the OUR SPACE data (e.g., low response rate). I also encountered significant political sensitivities with regard to reporting the findings to relevant stakeholders, potentially threatening the ability of internal researchers to carry out such research, as suggested by Universities UK. Despite these challenges, this research has the potential to impact the way policy makers and practitioners prioritise the problem of SV in the UK and inform the development of evidence-based programming to address and respond to the problem

    Contribution of poultry farm practice to the structure and composition of bacterial communities in the soil of poultry farms in Lagos, Nigeria

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    Background: Poultry farming practices can impact soil health by altering its microbial and organic composition. On one hand, this could improve soil fertility, but on the other, it may pose health risks to humans and the environment. In this study, we assessed the microbial community structure and composition of poultry litter impacted soil in poultry farms in Lagos Nigeria. Methods: Composite soil samples were collected from two farms (PF01A and PF02B) in a poultry estate and from a pristine environment (CTR) without farming activity. Metagenomic analysis was performed using 16S rRNA gene amplicon sequencing and bioinformatics analysis. Results: The most abundant phyla in poultry-impacted soils were Firmicutes (54–69%), Bacteroidetes (18–19%), and Actinobacteria (3–17%), with a low relative abundance of Proteobacteria (7%). In contrast, CTR soil was dominated by the phylum Proteobacteria (30%) and had a low relative abundance of Bacteroidetes (2%). Bacteria strains, including Jeotgalibaca arthritidis, Lysinibacillus jejuensis, and the novel species Enterococcus lemanii and Enterococcus eurekensis, were among dominant taxa in PF01A and PF02B.Some dominant bacterial species such as Corynbacterium xerosis and Ignatzschineria indica have been implicated in human infections and are known to be multidrug resistant. Conclusion: In this study, a high abundance of bacterial operational taxonomic units (OTUs) were found in soil from poultry farms. The presence of poultry litter significantly changed the composition of the bacterial community in the soil. This alteration did not only affect the microbial structure and health of the soil, it also increased the presence of clinically important bacteria, which could pose potential risks to public health

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