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Clinical utility of self-reported sleep duration and insomnia symptoms in type 2 diabetes prediction
Get PDFAims/hypothesis: Suboptimal sleep health is linked to higher risks for incident type 2 diabetes. We aimed to assess the clinical utility of adding self-reported sleep traits to a type 2 diabetes prediction model. Methods: In this cohort study, we used UK Biobank data and Cox proportional hazards models to examine how self-reported sleep duration and insomnia symptoms were associated with incident type 2 diabetes risk. Harrell’s C statistic and net reclassification improvement (NRI) were used to assess whether sleep traits improved the incident type 2 diabetes discrimination and predictive utility achieved using QDiabetes variables, with and without including a type 2 diabetes polygenic risk score (PGS). Independent replication was explored in the Nurses’ Health Study, the Nurses’ Health Study II and the Health Professionals Follow-up Study. Results: Extremes of sleep duration and occasional or frequent insomnia symptoms were associated with higher risks for incident type 2 diabetes. In the UK Biobank and replication cohorts, adding sleep traits to the QDiabetes risk score did not improve type 2 diabetes prediction (C statistic: QDiabetes alone 0.8933; QDiabetes + sleep duration 0.8939; QDiabetes + insomnia 0.8931; QDiabetes + sleep traits 0.8935). The corresponding total NRI values were: 0.08 (95% CI −0.18, 0.33), 0.04 (95% CI −0.08, 0.16) and 0.04 (95% CI −0.10, 0.18). Inclusion of PGS data marginally improved the type 2 diabetes risk prediction achieved using The QDiabetes calculator, with or without the inclusion of sleep traits in the model (QDiabetes + PGS: C statistic 0.8945; total NRI 0.20 [95% CI 0.12, 0.28]; QDiabetes + PGS + sleep traits: C statistic 0.8946; total NRI 0.18 [95% CI 0.09, 0.27]). Conclusions/interpretation: While sleep duration and insomnia symptoms were associated with type 2 diabetes risk, they are not useful for improving type 2 diabetes prediction beyond QDiabetes model performance. Inclusion of a type 2 diabetes PGS marginally improved prediction but lacked clear clinical utility. Graphical Abstract
Improving the sensitivity to neutrinoless double beta decay in SNO+
Get PDFSNO+ is a multi-purpose neutrino detector located 2 km underground in Sudbury, Canada. The inside of the detector is currently being filled with liquid scintillator, which will then be loaded with tellurium-130 in order to search for neutrinoless double beta decay (0νββ).
This thesis concerns itself with ways to improve the sensitivity of SNO+ to this process and achieves it in two ways. Firstly, it is demonstrated that an increase of the light output of 15−20% can be achieved with the addition of an amine to the tellurium-loaded scintillator mixture. The higher light output results in better energy resolution of the detector, which conversely translates in higher sensitivity to 0νββ. Furthermore, it is demonstrated that this addition is important for stabilisation of the tellurium-loaded scintillator with regards to water exposure. Secondly, the application of multi-site event classification techniques in signal extraction in SNO+ is discussed. A likelihood analysis including topological and timing pulse shape discrimination (PSD) parameters as additional observables is presented. These PSD parameters differentiate between interactions with point-like and multi-site energy depositions. Their use can therefore break the degeneracy between any "point-like" 0νββ signal and more distributed energy depositions from radioactive background decays involving γs, such as from cosmogenic or external sources. The resulting expected lower limit on 0νββ half-life is 1.80 ×10^26 years at 90% confidence after 3 years of data taking. Furthermore, it is demonstrated that this analysis would allow for a genuine 0νββ observation for effective Majorana mass of 75−181 meV at 99% confidence after 3 years, which is 40−50% lower than what is achievable without the inclusion of PSD
“Getting it right”: when and how extractive firms improve their human rights behaviour
No full textIn the aftermath of corporate scandals in the 1990s, including oil spills and violence against anti-mining protestors, various multi-stakeholder initiatives emerged to address corporate abuse within the extractive sectors worldwide. While some view these global human rights norms as significant progress, others raise concerns about firms adopting them superficially to enhance their image without genuinely transforming their human rights practices. But what about the rare case where a firm takes deliberate steps to improve its human rights behaviour? What conditions would prompt such shifts and how are they implemented?
Using Ghana as a country of study, I adopt a grounded mixed-method approach to investigate when and how extractive firms improve their human rights behaviour. By combining data from an originally constructed database with interviews, I uncovered patterns of corporate abuse within Ghana's extractive sectors and explored the corresponding remedies employed. I then closely examine the critical case of an extractive firm attempting to improve its past human rights records. My findings highlight an economic crisis that threatened the firm's survival as a pivotal catalyst (when) in prompting the human rights reforms. During the firm’s restructuring, internal change agents introduced (1) human rights awareness raising, (2) administrative and procedural changes, (3) personnel changes, and (4) changes to community engagement and development practices (how). Despite these improvements, perspectives from affected community members reveals unresolved tensions, with some demanding more substantial initiatives to promote the enjoyment of their economic, social, cultural, and solidarity rights.
This thesis makes important theoretical, empirical, and analytical contributions to the sociological literature on business and human rights. Firstly, it offers a grounded theory on extractive firms’ transition from abusing to respecting human rights. Empirically, it shows the possibilities and limits of becoming a more human rights-oriented extractive firm. Analytically, it explains why substantive changes to extractive firms' human rights practices remain the exception rather than the norm
Preliminaries to artificial consciousness: a multidimensional heuristic approach
Get PDFThe pursuit of artificial consciousness requires conceptual clarity to navigate its theoretical and empirical challenges. This paper introduces a composite, multilevel, and multidimensional model of consciousness as a heuristic framework to guide research in this field. Consciousness is treated as a complex phenomenon, with distinct constituents and dimensions that can be operationalized for study and for evaluating their replication. We argue that this model provides a balanced approach to artificial consciousness research by avoiding binary thinking (e.g., conscious vs. non-conscious) and offering a structured basis for testable hypotheses. To illustrate its utility, we focus on "awareness" as a case study, demonstrating how specific dimensions of consciousness can be pragmatically analyzed and targeted for potential artificial instantiation. By breaking down the conceptual intricacies of consciousness and aligning them with practical research goals, this paper lays the groundwork for a robust strategy to advance the scientific and technical understanding of artificial consciousness
Total cost of ownership of heat pumps and policy choice: the case of Great Britain
Get PDFHeat pumps are essential for decarbonizing heating, as shown by numerous studies. Their adoption depends significantly on economic attractiveness. Using Great Britain (GB) as a case study, this paper examines the total cost of ownership (TCO) for heat pumps versus gas boilers. TCO is calculated using official energy statistics, field trial data, and residential energy prices, alongside scenario analyses on business as usual, shifting levies from electricity bills to general taxation or to gas bills. Findings reveal that heat pumps provide cost savings for units performing at an above-average efficiency under standard tariffs but yield significant savings with smart tariffs. Results indicate that a carbon tax on gas, matching electricity permit prices, has limited impact. However, shifting levies from electricity to general taxation significantly enhances TCO compared to gas heating, with even greater incentives when levies are shifted to gas heating
Health and associated economic benefits of reduced air pollution and increased physical activity from climate change policies in the UK
Get PDFClimate change policies do not always include analysis of air quality and physical activity co-benefits. We compared business as usual (BAU) UK policy with Net Zero scenarios from the UK Climate Change Committee for road transport and building sectors. We quantified and monetised the health benefits of the Balanced Net Zero (BNZP) and Widespread Innovation (WI) Pathways.
Air pollution concentrations were predicted using Chemical Transport Models and population-weighted. Shifts from car to walking and cycling for transport were converted to METhrs/week. Literature concentration–response functions were combined with baseline rates from routine statistics/other sources. Mortality and multi-morbidity impacts were calculated using lifetable analysis, and an incidence/prevalence model from 2019 to 2154 (a lifetime after 2050). Monetary values were applied to the results.
The BNZP policy compared with BAU gave 4.9 (95 % confidence interval 1.0–9.0) million life-years gained (LYG) (UK population, to 2154), including 1.1 (0.7–1.6) million LYG from active travel improvements. Avoided COPD and childhood asthma cases were 201,000 (150,000 – 250,000) and 192,000 (64,600–311,000). The monetised air quality morbidity benefits (£52.1 (36.4 – 67.8) billion) substantially added to the air quality mortality benefits (£77.9 (42.9 to 90.8) billion). Total yearly monetised benefits for BNZP vs BAU summed to 2154 (air pollution/active travel) were £153 (122 to 184) billion (core); 278 (228 to 334) billion (+outcomes with weaker evidence).
Adding the effects of air pollution reductions on disease incidence, with effects of air pollution and physical activity on mortality, increases the monetised benefits that may justify Net Zero policies in cost-benefit analysis
Spatial, social and environmental drivers of the timing of reproduction in the wild
Get PDFPhenotypic variation provides the raw material needed for natural selection, and therefore identifying what causes and maintains this variation is important for understanding ecological and evolutionary processes. Behavioural timing traits, such as when an individual begins breeding during the reproductive season (often referred to as phenology), often show continuous variation between individuals within populations. Like any quantitative trait, this variation is influenced by both genetic and environmental factors, but disentangling their respective contributions can be challenging. Estimating the genetic contribution requires careful consideration of environmental effects across suitable scales. The environment experienced by individuals will encompass both physical and social factors, and will often vary over small scales. The study of small-scale environmental (both physical and social) effects on phenotypic variation is becoming a growing area of interest and is widely recognised as important for determining the causes and consequences of phenotypic variation between individuals. To explain the phenotypic variation observed in phenological traits there must be consideration of 1) environmental factors at the appropriate spatial scale and 2) the social dependence of these responses, both of which I address in this thesis. Our study system, a long-term monitored population of great tits in Wytham Woods, Oxford, UK, provides a robust dataset for investigating these questions. This population has been monitored extensively for over 60 years, with detailed data collected on individual birds’ breeding attempts every spring, offering unique insights into the drivers of variation in a seasonal timing trait. First, in Chapter 2, I used multi-matrix quantitative genetic animal models to quantify the relative contributions of additive genetic and environmental factors to phenotypic variation, accounting for similarities between the local environment of individuals by modelling spatial proximity and breeding environment similarity. I found that the environment experienced by individuals explains around a fifth of the variation seen in reproductive timing, and accounting for this leads to decreased estimates of heritability. In Chapter 3, I considered the social influence on breeding timing and explored how the age of neighbouring individuals in the population affects the variation seen in timing, drawing conclusions on the possible effect of neighbouring birds on a focal bird’s timing decisions. I found that adults breed relatively later when their neighbours are also adults, but no evidence that local age structure affects juvenile timing. This may indicate that juveniles do not use social cues from older more experienced birds to time breeding, potentially due to limited phenotypic plasticity. In Chapter 4, I look at the influence of familiarity with breeding partners and breeding sites on breeding timing. I find that birds with either familiar partners, or birds nesting in a familiar nest box, lay earlier relative to a population level measure of laying date. The same pattern was found when considering laying date as mismatch to a local laying average. Interestingly, I found there is however no evidence of an additive effect of having both a familiar partner and nest box, but instead it appears that familiarity with either advances laying similarly. Finally, in Chapter 5, I explore the ecological and individual drivers of multiple breeding attempts within seasons, and discuss how this might be important as a reproductive strategy. I found the occurrence of second breeding attempts in this population is non-random in regards to when individuals are initiating them, and appears to be shaped by individual factors, including age and timing of first-brood failure. I then bring all these areas together in Chapter 6 and discuss how this thesis impacts our knowledge about the causes of intraspecific variation in this population, and what this might mean for other phenological traits more broadly too
Private by default: reasonable expectations in secondary uses of patient data
Get PDFThe ‘reasonable expectations of privacy’ test has become central to English information law. The fact-specificity of this test has obfuscated the scope of patients’ privacy rights. In both R (W, X, Y & Z) v Secretary of State for Health and Prismall v Google, the claimants were found to lack a circumstantially reasonable expectation of privacy when their identifiable information was disclosed outside the healthcare system, obviating the need for justification under Article 8 European Convention on Human Rights (ECHR). In response to these developments, this article argues for a legal presumption of privacy when patients’ data are used for purposes other than their healthcare. This would be a development of the courts’ existing ‘starting point’ of assuming reasonable expectations of privacy in identifiable medical information. The two cases explored in this article suggest that this ‘starting point’ is not enough, and still affords judges broad discretion to evaluate a (non-exhaustive) list of factors in each individual case. For the sake of the clarity and accessibility of patients’ rights, I argue that privacy should be presumed by default when their data are used for purposes other than their healthcare
The Central Cemetery at Ingombe Ilede, Zambia: Chronology and Connections
Get PDFIngombe Ilede is located just north of the Zambezi River, and has often been seen as a trading station connected to Central Africa, the Zimbabwe Plateau and the Indian Ocean. Discussion of the richly appointed burials in its Central Cemetery has been hindered by uncertainty over their ages. In this article, we report four new radiocarbon dates from Ingombe Ilede and six new dates from sites in northern Zimbabwe that are relevant to a wider understanding of Ingombe Ilede and its connections. These ten dates are all on organic fiber cores within copper and bronze jewelry, for which we also report chemical compositions, lead isotope ratios, and (for bronzes) tin isotopic ratios. We show that the richer burials in the Central Cemetery were interred no earlier than the mid fifteenth century. By this time copper from the Central African Copperbelt, 500–700 km north of the Zambezi, had been transported into northern Zimbabwe for at least two centuries, as had tin from the Bushveld Large Igneous Province (BLIP) 900–1000 km south of the Zambezi. The rich burials at Ingombe Ilede represent a late phase of a longstanding trade in copper from the Copperbelt to the Zimbabwean plateau
CircANKRD52 Augments the Growth and Invasion of Melanoma Cells by Sponging miR ‐141‐3p and Upregulating PRKACB
Get PDFAccumulating data have shown that circRNAs act pivotal roles in cancer progression. However, the role and molecular mechanism of circRNAs in melanoma remain undocumented. GEO dataset was used to identify the differentially expressed circRNAs between melanoma and normal tissues, and the expression and prognosis of circANKRD52 (hsa_circ_0026926) in melanoma were assessed by qRT‐PCR analysis. EdU, Transwell, Flow cytometry analysis, human umbilical vein endothelial cells (HUVECs) coculture assay as well as in vivo tumourigenesis models were utilised to assess cell growth and invasion. The specific binding between circANKRD52 and miR‐141‐3p was confirmed by bioinformatic analysis, RIP, RNA pull‐down, and luciferase reporter assays. The effect of circANKRD52 or miR‐141‐3p on PRKACB expression was evaluated by Western blot assay. We found that circANKRD52 was upregulated in melanoma tissue samples and cell lines and associated with poor survival and tumour recurrence in patients with melanoma. Knockdown of circANKRD52 repressed the growth and invasion of melanoma cells in vitro and in vivo, whereas ectopic expression of circANKRD52 promoted these effects. Moreover, circANKRD52 could bind to miR‐141‐3p, leading to upregulation of PRKACB, and downregulation of miR‐141‐3p restored melanoma cell growth and invasion. Our findings demonstrate that circANKRD52 promotes the growth and angiogenesis of melanoma cells by sponging miR‐141‐3p and upregulating PRKACB