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    Essays in Macroeconomics: Consumption, Fiscal Multipliers, and Oil Prices

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    This thesis, titled Essays in Macroeconomics: Consumption, Fiscal Multipliers, and Oil Prices, contains three papers in the broad macroeconomics field three chapters. Three abstracts of the papers have been presented here. Chapter 1 aims to investigate the response of consumption to transitory shocks in a heterogeneous agent model with two assets and default risk. In order to analyse this response, the paper studies the application of discrete choice techniques (Extreme Value Shocks Method/Taste Shocks Method) in several versions of the model. The method appears to be reliable in capturing the effect of endogeneity of the borrowing constraint due to default in both the one-asset and two-asset models. The baseline results show that the presence of default raises the aggregate marginal propensity to consume as the pricing of risk creates further credit frictions for many households. Furthermore, the findings also suggest that households' responses vary more widely across heterogeneous households if there are endogenous borrowing constraints and spreads. Keywords: Heterogeneous agent model, MPC, Tasteshock, Liquid/illiquid asset, Default. Chapter 2 examines the effects of social spending on GDP growth in the UK economy. The Structural Vector Autoregressive (SVAR) method with sign restriction has been applied to quarterly data for 27 years in order to assess the impact of social expenditure shocks on economic growth. The study suggests that a positive shock in social spending increases GDP growth in the short term. In addition, results are robust to different countries and under different monetary policies. Furthermore, the analysis found that negative tax shock also has a positive impact on GDP. Keywords: Social spending, GDP growth, Structural Vector Autoregressive (SVAR), Sign restriction. Chapter 3 investigates the influence of the pandemic and trade policy uncertainty on the dynamics of oil price returns over the last two decades, using a Mixed-Frequency Vector Autoregressive (MF-VAR) model. The study found that pandemic uncertainty and, more importantly, trade policy uncertainty significantly explain EU Brent and WTI oil price returns. Additionally, pandemic and trade policy uncertainty shocks are linked with lower (higher) oil price returns in the short-term (medium-term). Furthermore, while the mixed-frequency approach captures the persistent response of oil price returns to the uncertainty shocks, the single common-frequency (i.e., quarterly) framework only uncovers a muted reaction. Keywords: Oil price fluctuations, Pandemic uncertainty, Trade policy uncertainty, World uncertainty, Mixed-frequency VAR model, Mixed-frequency Granger-causality test

    The role of cardiovascular multimodality imaging in the evaluation of Anderson-Fabry disease: from early diagnosis to therapy monitoring A clinical consensus statement of the ESC Working Group on Myocardial & Pericardial Diseases and the European Association of Cardiovascular Imaging of the ESC.

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    Anderson-Fabry disease (AFD) is a rare genetic disease with X-linked transmission characterized by a defect in the enzyme alpha-galactosidase A (alpha-GAL), which impairs glycosphingolipid metabolism and leads to an excessive storage of globotriaosylceramide (Gb3) within lysosomes. AFD involves renal, cardiac, vascular, and nervous systems and is mainly observed in male patients with onset in childhood, although cardiac manifestation is often shown in adults. AFD cardiomyopathy is caused by the accumulation of Gb3 within myocytes first showed by left ventricular (LV) hypertrophy and diastolic dysfunction, leading to restrictive cardiomyopathy and systolic heart failure with biventricular involvement. The diagnosis of AFD cardiomyopathy may be insidious in the first stages and requires accurate differential diagnosis with other cardiomyopathies with hypertrophic phenotype. However, it is fundamental to promptly initiate specific therapies that have shown promising results, particularly for early treatment. A careful integration between clinical evaluation, genetic tests, and cardiac imaging is required to diagnose AFD with cardiac involvement. Basic and advanced echocardiography, cardiac magnetic resonance, and nuclear imaging may offer pivotal information for early diagnosis (Central illustration) and the management of these patients is often limited to centres with high expertise in the field. This clinical consensus statement, developed by experts from the European Society of Cardiology (ESC) Working Group on Myocardial & Pericardial Diseases and the European Association of Cardiovascular Imaging of the ESC, aims to provide practical advice for all clinicians regarding the use of multimodality imaging to simplify the diagnostic evaluation, prognostic stratification, and management of cardiac involvement in AFD

    You’ve got a friend in me: Deciphering the genomics of host empowerment by symbiotic microbes

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    Animals have established unique symbiotic associations with microbial partners that improve their life history traits. We have started to gain appreciation of animals as metaorganisms, in conjunction with their associated microbiome, as an intertwined system that operates in a concerted effort. Multiple fitness benefits have been observed in animals that have established symbioses with particular microbial symbionts, yet the genetic mechanisms underlying these drastic phenotypic shifts remain unexplored. Here I show the genomic mechanisms by which symbiotic microbes empower their host animals. I explore how, in the marine environment, the endosymbiotic Oceanospirillum enables the bone eating worm Osedax to feed on whale bones, and how the metabolic differences in the ectosymbionts of Osedax make them a de facto second skin cloaking the sessile animal in its harsh environment. In the terrestrial world of aphids, I uncover how this successful agricultural pest avoids parasitism by its natural enemy through hosting special strains of H. defensa that carry toxins with unique specificity to the larvae of its enemy. I also explore the genomic intricacies that shaped the evolution of the symbiont Regiella insecticola which has one of the broadest portfolios of phenotypic advantages conferred to its hosts

    Prolonged persistence of mutagenic DNA lesions in somatic cells.

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    DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment1-3. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours3,4, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium5-12. Persistent DNA lesions occurred at increased rates, with distinctive mutational signatures, in donors exposed to tobacco or chemotherapy, suggesting that they can arise from exogenous mutagens. In haematopoietic stem cells, persistent DNA lesions, probably from endogenous sources, generated the characteristic mutational signature SBS1913; occurred steadily throughout life, including in utero; and endured for 2.2 years on average, with 15-25% of lesions lasting at least 3 years. We estimate that on average, a haematopoietic stem cell has approximately eight such lesions at any moment in time, half of which will generate a mutation with each cell cycle. Overall, 16% of mutations in blood cells are attributable to SBS19, and similar proportions of driver mutations in blood cancers exhibit this signature. These data indicate the existence of a family of DNA lesions that arise from endogenous and exogenous mutagens, are present in low numbers per genome, persist for months to years, and can generate a substantial fraction of the mutation burden of somatic cells

    Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies.

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    In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses. The associations are enriched for antidepressant targets and provide potential repurposing opportunities. Polygenic scores trained using European or multi-ancestry data predicted MD status across all ancestries, explaining up to 5.8% of MD liability variance in Europeans. These findings advance our global understanding of MD and reveal biological targets that may be used to target and develop pharmacotherapies addressing the unmet need for effective treatment

    Using Serious Games for Learning Business Ethics: Exploring its Socio-Technical Enablers and Cross-Cultural Influences

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    This article investigates the impact of socio-technical and cultural factors on business management students’ learning of ethical skills in a serious gaming environment. A survey study (n=302) was conducted with participants from two British universities. SEM (structural equation modelling) was used to test the empirical model, and the results of this study show that technical enablers and social enablers impact learners’ performance and perception of serious games as pedagogically effective learning tools. Additionally, we observe cultural differences in learners’ conative behaviour towards serious games when learners are drawn from Anglo and Confucian cultures, high-performance and low-performance orientation cultures, and emotionally oriented shame and guilt cultures. By applying and extending the socio-technical theory of information systems to a serious gaming environment, this article has identified some key social-technical and cultural enablers that can influence and facilitate the adoption of serious games as an effective practice-based learning or training instrument

    Understanding and Improving User-controlled Content Moderation Systems on Social Media

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    This thesis presents a comprehensive exploration of the design and execution of user-controlled content moderation systems that prioritize both fairness and efficiency. These systems range from decentralised blocklists on Twitter to Web3 content moderation (referred to as ''mute'') on memo.cash. memo.cash is a microblogging platform built on the Bitcoin Cash (BCH) blockchain and stands out as the only Web3 platform that enables user-to-user moderation. In contrast, other Web3 platforms like Steemit and Noise.cash employ a less decentralized approach, involving community moderators and administrators. Through extensive data mining, encompassing social interactions and moderation actions from 2.8 million Twitter users and 24 thousand memo.cash users, a thorough analysis of user behaviour among moderated users and moderators, and in-depth machine learning classification and moderation recommendation, this research offers insights into the perspectives and practices of various stakeholders. These stakeholders include users who invest time or financial resources in moderation and individuals whose timelines are affected by content hiding. This study not only furnishes theoretical insights but also offers practical guidance. It prompts the challenges of individual users engaging in moderation while upholding the principles of free speech. It also delves into designing solutions that cater to the diverse needs of user groups and the integration of automated moderation tools

    Exploring the policy implementation of a holistic approach to cancer investigation in non-specific symptom pathways in England: An ethnographic study.

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    OBJECTIVES: This study aimed to explore the policy implementation of non-specific symptom pathways within the English National Health Service. METHODS: A multi-site ethnographic project was conducted in four hospitals that contained non-specific symptom pathways between November 2021 and February 2023. The research involved observation (44 h), interviews (n = 54), patient shadowing, and document review. RESULTS: The study examined how the policy concept of 'holistic' care was understood and put into practice within four non-specific symptom pathways. Several challenges associated with providing holistic care were identified. One key challenge was the conflict between delivering holistic care and meeting timed targets, such as the Faster Diagnosis Standard, due to limited availability of imaging and diagnostic tools. The interpretation of a holistic approach varied among participants, with some acknowledging that the current model did not recognise holistic care beyond cancer exclusion. The findings also revealed a lack of clarity and differing opinions on the boundaries of holistic care, resulting in wide variation in NSS pathway implementation across health care providers. Additionally, holistic investigation of non-specific symptoms in younger patients were seen to pose difficulties due to younger patients' history of health anxiety or depression, as well as concerns over radiological risk exposure. CONCLUSIONS: The study highlights the complexity of implementing non-specific symptom pathways in light of standardised timed cancer targets and local cancer policies. There is a need for appropriately funded organisational models of care that prioritise holistic care in a timely manner over solely meeting cancer targets. Decision-makers should also consider the role of non-specific symptom pathways within the broader context of chronic disease management, with a particular emphasis on expanding diagnostic capacity

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