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Measuring carbon capability beyond the carbon footprint
Get PDFMeeting climate action targets requires both individual and systemic change. Behaviour change can contribute to system change through actions in the public sphere, including influence and citizenship. However, current measurement approaches, such as personal carbon footprints, emphasise individual consumption and underrepresent public-sphere contributions. This study operationalises a framework which integrates individuals’ motivation and capacity to reduce emissions within broader systems of provision. We present a methodology to quantify public-sphere actions and capabilities alongside consumption behaviours, generating a comprehensive capability score. Applying this approach to a representative survey UK residents (N = 2001), we find moderate-to-low climate action capability, with the lowest scores in transport, food, and civic domains. Regression analyses indicate gender, education, and climate knowledge predict higher capability. This methodology offers an integrated tool to assess both private and public climate actions, informing strategies for more effective engagement and policy interventions
Controlled Human Infection of Healthy Adults With Lyophilized Neisseria lactamica Induces Asymptomatic, Immunogenic Nasopharyngeal Carriage in the United Kingdom and Mali
Get PDFBackground: Carriage of Neisseria lactamica (Nlac), a harmless nasopharyngeal commensal, correlates inversely with carriage of Neisseria meningitidis (Nmen), a common cause of meningitis and sepsis outbreaks in sub-Saharan Africa. Nasally administered lyophilized Nlac (LyoNlac) might interrupt carriage and transmission of Nmen in sub-Saharan settings without requirement of a cold chain, but whether LyoNlac can establish colonization is undetermined. Methods: Healthy adult volunteers aged 18–45 years were inoculated intranasally with 104–107 colony forming units (CFU) of reconstituted, lyophilized Nlac strain Y92-1009 (LyoNlac) in 2 dose-ranging controlled human infection studies conducted in the United Kingdom and Mali. Safety was measured as a primary objective. Secondary objectives included the dose achieving ≥70% colonization rates for each setting, colonization kinetics, and serological responses. Both trials were registered with ClinicalTrials.gov (United Kingdom: NCT04135053, Mali: NCT04665791) and are complete. Results: Intranasal inoculation with LyoNlac was well tolerated with no significant safety concerns. In the United Kingdom, 105 CFU yielded 100% colonization (n = 10/10) while in Mali, 107 CFU achieved 65% colonization (n = 13/20). An increase in Nlac- and Nmen-specific IgG from pre-challenge to day 28 post-challenge was observed in colonized participants—median fold-change [interquartile range] United Kingdom: Nlac 2.24 [1.37–4.24], Nmen 1.39 [1.20–3.70] and Mali: Nlac 1.31 [1.04–1.94], Nmen 1.32 [0.99–1.73]. No significant seroconversion occurred in non-colonized participants. Conclusions: Intranasal inoculation with LyoNlac was safe and induced immunogenic nasopharyngeal colonization in healthy adults in the United Kingdom and Mali. Future clinical trials to determine whether LyoNlac reduces meningococcal carriage and transmission in the meningitis belt are warranted
Dairy consumption and risk of cardiometabolic diseases: a prospective cohort study of the China Kadoorie Biobank
Get PDFBackground: Previous evidence on the associations of dairy intake with risk of cardiometabolic diseases has been inconsistent with studies showing either inverse, null or positive associations. Objective: We aimed to assess these associations in China, where dairy consumption level is low and cardiometabolic disease patterns differ from those in the West. Methods: The China Kadoorie Biobank is a prospective cohort study with ~512,000 adult participants recruited from ten diverse localities in China during 2004-08. At baseline and periodic resurveys, information on the consumption frequency of major food groups was collected using a validated interviewer-administered laptop-based questionnaire. During approximately 5.4 million person-years of follow-up, 18,306 diabetes, 33,946 ischemic heart diseases (IHD, including 3888 acute myocardial infarction [MI]), 33,670 ischemic stroke (IS), 7191 intracerebral haemorrhage (ICH) cases, and 13,241 cardiovascular deaths were recorded. Cox regression was used to calculate adjusted hazard ratios (HRs) relating dairy intake to cardiometabolic diseases risk. Results: At baseline, 10.7% of participants regularly consumed (i.e. ≥4 days/week) dairy products, while 70.0% reported never or rare consumption. After adjusting for potential confounders including BMI, dairy consumption was significantly and positively associated with IHD but inversely associated with risks of acute MI, ICH and cardiovascular death, with HRs for regular consumers vs non-consumers being 1.09 (95% CI: 1.06-1.12), 0.88 (0.80- 0.98), 0.69 (0.62-0.76) and 0.82 (0.77-0.87), respectively, but not with diabetes and IS. These associations were largely independent of systolic blood pressure. Conclusions: In Chinese adults, higher dairy consumption was associated with lower risks of acute MI, ICH and cardiovascular death. Future studies are warranted to further elucidate these relationships and their causalit
Algorithmic fairness and bias mitigation in clinical machine learning for equitable patient outcomes
Get PDFIn recent years, the integration of machine learning algorithms into clinical settings has shown immense potential for improving healthcare outcomes. However, concerns regarding fairness and equity in machine learning models have garnered increasing attention, particularly in healthcare where biased algorithms can perpetuate existing disparities. This thesis investigates the role of fairness-aware algorithms in addressing these issues within clinical machine learning applications. Through case studies and empirical analyses, this research explores how biases manifest and impact model performance across diverse patient populations, highlighting the challenges and opportunities in promoting fairness within clinical machine learning. Subsequently, drawing on datasets from multiple healthcare institutions, we propose and assess the effectiveness of fairness-aware techniques in advancing equitable healthcare outcomes. Ultimately, this thesis contributes to the ongoing dialogue on fairness in machine learning, providing insights and recommendations for the development of ethically sound and socially responsible machine learning algorithms in healthcare
Fast policy learning for linear-quadratic control with entropy regularization
No full textThis paper proposes and analyzes two new policy learning methods, regularized policy gradient and iterative policy optimization (IPO), for a class of discounted linear-quadratic control (LQC) problems over an infinite time horizon with entropy regularization. Assuming access to the exact policy evaluation, both proposed approaches are proved to converge linearly in finding optimal policies of the regularized LQC. Moreover, the IPO method can achieve a superlinear convergence rate once it enters a local region around the optimal policy. Finally, when the optimal policy for a reinforcement learning (RL) problem with a known environment is appropriately transferred as the initial policy to an RL problem with an unknown environment, the IPO method is shown to converge at a superlinear rate if the two environments are sufficiently close. A model-free version of the policy-based methods is also discussed. Performances of these proposed algorithms are supported by numerical examples
Bringing External Validity into Sociological Research
Get PDFThe so-called causal revolution that has spread through economics and into adjacent social sciences, including sociology, has been very much concerned with developing methods by which to arrive at credible causal estimates, especially in nonexperimental, observational settings. In the language of experiments, it has focussed on internal validity. But much less attention has been paid to external validity, that is, whether a causal relationship holds in situations other than the one in which it was found. Thinking about external validity obliges us to consider why we are trying to estimate causal relationships in the first place, and what we think they are for. In this paper we discuss in greater detail what we mean by internal and external validity and set out the assumptions required for causal estimates to have both. We consider some examples from sociological research and the challenges to external validity that they illustrate. We urge sociologists, especially those engaged in nonexperimental research, to pay more attention to external validity. But we also stress that this is important not only for causal research but also for other research, and we illustrate issues of external validity that may arise in a wide variety of noncausal studies. We conclude with some practical suggestions and remarks concerning some of the general issues that arise from our work
The Mitochondrial Guardian α‐Amyrin Mitigates Alzheimer's Disease Pathology via Modulation of the DLK‐SARM1‐ULK1 Axis
Get PDFHigh consumption of colorful fruits and vegetables correlates with low dementia risk, but the exact molecules and the underlying biological mechanisms governing their bioactive profiles are largely unknown. Using a 10‐year observational cohort study coupled with an AI‐driven systems pharmacology platform, we identified a natural triterpenoid compound found in colorful fruits and vegetables, α‐Amyrin (αA), as a therapeutic candidate for Alzheimer's disease (AD). The efficacy of αA in treating the symptoms of AD, such as Tau tangles, damaged mitochondria, and memory loss, was examined using cross‐species models; αA retained memory in AD‐like animal models while also strongly inhibiting Tau pathology, especially p‐Tau217, in a cellular ‘Tau seeding’ system and in Tau[P301S] mice, followed by validation using a human 3D microfluidic system. At molecular level, αA is a robust mitochondrial regulator, enhancing mitochondrial stress resilience and activation of mitophagy. Mechanistically, αA inhibits dual leucine zipper kinase (DLK), leading to the inhibition of DLK‐Sterile Alpha and TIR Motif Containing 1 (SARM1)‐dependent neurodegeneration; this inhibition frees unc‐51 Like Autophagy Activating Kinase 1 (ULK1) from the ULK1‐SARM1 complex, allowing it to participate in autophagy/mitophagy. αA also shows strong translational potential with a 10.1 h half‐life and the ability to cross the blood‐brain barrier. Our results indicate that αA may act as a mitochondrial guardian against AD via modulating the DLK‐SARM1‐ULK1‐autophagy/mitophagy axis while further preclinical and clinical studies are warranted
Machine learning for enzyme catalytic activity: current progress and future horizons
Get PDFEnzyme catalysis, with its advantages in environmental sustainability and efficiency, is gaining traction across diverse industrial applications, such as waste utilization and pharmaceutical biomanufacturing. However, optimizing enzyme catalytic activity remains a significant challenge. To facilitate enzyme mining and engineering, machine learning (ML) models have emerged to predict enzyme substrate specificity, enzyme turnover number, and enzyme catalytic optimum. This review endeavored to assist researchers in effectively utilizing predictive models for enzyme catalytic activity through presenting recent advancements and analyzing different approaches. We also pointed out existing limitations (e.g. dataset imbalance) and offered suggestions on potential enhancements to address them. We identified that the attention mechanism, inclusion of new features such as product information and temperature, and using transfer learning to leverage different datasets were three main useful modeling strategies. Furthermore, we envisaged that accurate predictors of enzyme catalytic activity would potentially transform enzyme and metabolic engineering, and the optimization of biocatalysis
Multimodal interpretation of notation
Get PDFChallenges related to the teaching and learning of formal notation in school mathematics are widely documented, and specifically in relation to the underlying mathematical structures that the notation is intended to convey. In this article, we draw on embodied cognition to examine the interactions among three students working with the software Grid Algebra. Embodied cognition emphasises the role of gesture and movement in learning and understanding mathematics. Grid Algebra uses movement to direct students’ attention to mathematical operations on numbers and numerical expressions within the grid and the structure of these operations, while the software takes care of the formal notation of the numerical expressions that describe these sequences of operations. We analyse how different modes of communication work together to scaffold students’ fluency with operations and the formal notation representing these operations and the order in which they are performed. The dynamic between notation, speech, movement and position allows students to educate their interpretation of mathematical notation through the movements and positions that they are very familiar with
Aquinas on definition and essence
Get PDFThe thesis presents a systematic investigation into Thomas Aquinas’s metaphysical essentialism by focusing on his interpretation of Aristotle’s Metaphysics Z. The investigation is centered on Aquinas’s interpretation of the ’notion of the ‘logical mode’ that opens Aristotle’s treatment of essence in Z 4. While much of the scholarly tradition has interpreted Aquinas’s modus logicus as either preliminary or dialectical in nature, my work argues that Aquinas method is demonstrative and properly applied to the metaphysical field: it employs logical intentions as valid starting points for metaphysical conclusions. Chapter 1 provides a conceptual and textual foundation for the modus logicus, arguing against its reduction to dialectics and showing its legitimacy as a metaphysical method.Chapter 2 examines Aquinas’s treatment of essence in terms of per se predications and real definitions in his Commentary on Z 4, identifying a set of logical and definitional criteria labelled under the Predicative Simplicity Criterion (PSC). These criteria establish the conditions for something X to be the essence of Y. Eventually, the treatment of Aquinas’s Commentary on Z 4 is integrated with a passage from Summa Contra Gentiles II, 58, where Aquinas argues in modus logicus from the reality of per se1 predications to the reality of the ontological unity of the essence. I call it the Predicative Simplicity Argument (PSA). Chapter 3 investigates the problem of the hylomorphic composition of sensible essences in Aquinas’s interpretation of Z 10-11, showing how Aquinas applies his modus logicus to prove the reality of prime matter and the necessarily enmattered character of a sensible essence. This leads to a metaphysical account of essence as a unified and simple principle, despite its composite nature. Aquinas’s perspective on Z 10-11 is also critically compared with some contemporary Aristotelian interpreters. Chapter 4 analyzes Aquinas’s Commentary on Z 12 and his solution to the problem of the unity of a genus+differentia definition. I show how the logical problem of the unity of the definition can be solved by showing its fundamental relation with the unity of the hylomorphic essence. I call Aquinas’s model of the unity of the definition UTM (Unitarian Transformative Model). As a matter of fact, Aquinas’s elaboration has a striking similarity with the discussions in contemporary ethics and philosophy of mind on additive vs transformative accounts of human rationality