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Avoiding unintentionally correlated shocks in proxy vector autoregressive analysis
Get PDFNoting that the shocks in vector autoregressive models can be correlated if a number of shocks is identified individually by multiple proxy variables, we propose a Generalized Method of Moments (GMM) approach for estimation that enforces uncorrelated shocks. We point out that if each proxy identifies exactly one shock and is uncorrelated with all other shocks, uncorrelatedness of the shocks provides over-identifying restrictions that can be used in our approach to improve the estimation efficiency of the structural parameters. It also opens up the possibility to use Hansen’s J-test to check the model specification. Our method generalizes other GMM proposals that work under more restrictive assumptions. We illustrate its usefulness by two empirical examples from the recent literature
Understanding excessive sleep in people with psychotic disorders
No full textBackground: There has been increasing attention to sleep disturbances such as insomnia in psychosis, due to its impact on symptoms, well-being, and recovery. However, excessive sleep and extended sleep duration are common in psychosis (partly linked to sedating antipsychotic medication) and have been relatively neglected, despite plausible interactions with symptoms, functioning, and broader well-being. Aim: This study aimed to explore the experience of extended sleep duration and excessive sleepiness, or their combination (hypersomnia) in people with psychotic disorders through a qualitative interview around the experience, impacts, contributors, and role of treatment. Method: Ten patients experiencing excessive sleep (defined as excessive daytime sleepiness >3 days a week; extended sleep duration of > 11 h in 24 h or >9 h at night; or a combination of these) alongside a diagnosed psychotic disorder were recruited. They met with the researcher online to participate in a semi-structured interview, which was analysed using thematic analysis. Results: Five major themes were developed: (1) The Exhausting Everyday, (2) Medication is the story? (3) Indescribable Tiredness, (4) Overruled by Sleep and (5) An Unfair Fight. Excessive sleep impacts multiple domains of individual well-being and recovery – for example, limiting patients in everyday tasks and socializing. Cycles of emotional avoidance and inactivity were identified as potential maintainers or exacerbators of excessive sleep, in addition to medication side effects. Patients reported difficulty conveying the impact of their sleepiness symptoms to clinicians or others. Conclusion: The results support that excessive sleep requires further attention as a problematic and impactful sleep presentation in this group. Further research is needed to improve recognition and assessment of problematic excessive sleep, and how existing practices or novel treatments may be applied to reduce its impact on recovery
0 to 9 and the New York Avant-Garde:Publishing by Numbers
No full textEdited and self-published by Bernadette Mayer and Vito Acconci from 1967 to 1969, 0 to 9 not only documented some of the most compelling examples of intermedia performance, contemporary poetry, and post-formalist art of the period, but also pioneered new ways of conceiving (and using) the magazine as medium and instrument. 0 to 9 and the New York Avant-Garde: Publishing by Numbers examines how the magazine both responded to and helped shape key developments in New York’s often fractious avant-garde communities. The book pays particular attention to the ways in which Mayer and Acconci foregrounded the material and generic qualities of the magazine and conceived their periodical as a means of generating (as well as documenting) art and poetry. 0 to 9 and the New York Avant-Garde considers the ways in which 0 to 9 interacted with other artistic movements and theoretical concerns of the period—including cybernetics, Pop Art, structuralism, and information theory. Arguing for the enduring importance of the magazine, and its unique position in the history of New York’s experimental art and literary scenes, this study contends that 0 to 9 was both a swan song of 1960s idealism and a precursor for the directions that avant-garde art would take in the decades that followed the magazine’s demise
Process-based machine learning observationally constrains future regional warming projections
Get PDFWe present the results of a novel process-based machine learning method to constrain climate model uncertainty in future regional temperature projections. Ridge-ERA5 - a ridge regression model - learns coefficients to represent observed relationships between daily near-surface temperature anomalies and predictor variables from ERA5 reanalysis in Northern Hemisphere land regions. Combining the historically constrained Ridge-ERA5 coefficients with inputs from CMIP6 future projections enables a derivation of observational constraints on regional warming. Although the multi-model mean falls within the constrained range of temperatures in all tested regions, a subset of models which predict the greatest degree of warming tend to be excluded and decomposition of the constraint into predictor variable contributions suggests error-cancellation of feedbacks in some models and regions
Imagining Responsible and Just Smart Home Technologies: Troubling Sociotechnical Systems Through Co-Design
Get PDFSmart home technologies (SHTs) are prominently featured in energy transition plans due to their potential to mitigate climate change effects. The representation of SHTs and their associated imaginaires significantly shapes perceptions and technology development. However, mass adoption of these technologies risks deepening social inequalities, enabling pervasive surveillance, and worsening environmental impacts. Previous studies involving users to foresee undesirable technology impacts fail to challenge industry solutionism effectively. This thesis reports on a co-design process organised to trouble dominant unfair sociotechnical systems behind SHTs, aiming to foster a more responsible and just imaginaire for the technology.
Working with 22 co-designers grouped as professionals, early adopters, and late adopters of SHTs, the study included five exploratory and speculative design workshops, an online focus group, and 14 evaluative interviews, analysed through qualitative coding and visual analysis. The co-design process uncovered three key insights: (i) prevalent techno-positivism exists in the imaginaires across different adopter groups and expert circles; (ii) issues with SHTs are systemic, impacting devices and usability, production and consumption, and the broader relationship between people and technology; (iii) when enacted through a democratic participation infrastructure focusing on mutual learning, co-design can disrupt unequal power dynamics, leading to more responsible and equitable outcomes associated with SHTs.
Co-design can enhance distinct social groups' abilities to critically represent alternative imaginaires. Viewing participants as partners rather than research subjects fosters a different relationship between industry and users, challenging dominant sociotechnical systems. This thesis presents three contributions: (a) conceptual framing SHT through its troubles instead of promised solutions; (b) maintaining engagement with SHT troubles via a non-solutionist co-design methodology; and (c) evidencing participants’ journeys of critical consciousness in co-designed speculative artefacts. Without challenging broader systemic and power dynamics, participatory practices like co-design risk perpetuating the same injustices produced by mainstream design
Taking the Colonial Bull by the Horns:The Everyday Aspirations and Resistance of Disabled and Black Students in Nigerian and South African Universities
No full textIn this chapter, we examine students' aspirations for a decolonised higher education through the quotidian demands of racial and disabled identities within higher education (HE) institutions in South Africa and Nigeria. We frame aspiration as a phenomenon that embodies the dreams and goals of students, and in their absence, focus on achievement and progress diminishe
Weberviruses are gut-associated phages that infect Klebsiella spp
Get PDFWeberviruses are bacteriophages (phages) that can infect and lyse clinically relevant, multidrug-resistant (MDR) strains of Klebsiella. They are an attractive therapeutic option to tackle Klebsiella infections due to their high burst sizes, long shelf life, and associated depolymerases. In this study, we isolated and characterized seven new lytic phages and compared their genomes with those of their closest relatives. Gene-sharing network, ViPTree proteome, and terL gene-sequence-based analyses incorporating all publicly available webervirus genomes [n = 258 from isolates, n = 65 from metagenome-assembled genome (MAG) datasets] confirmed the seven phages as members of the genus Webervirus and identified a novel genus (Defiantjazzvirus) within the family Drexlerviridae. Using our curated database of 265 isolated phage genomes and 65 MAGs (n = 330 total), we found that weberviruses are distributed globally and primarily associated with samples originating from the gut: sewage (154/330, 47%), wastewater (83/330, 25%), and human faeces (66/330, 20%). We identified three distinct clusters of potential depolymerases encoded within the 330 genomes. Due to their global distribution, frequency of isolation and lytic activity against the MDR clinical Klebsiella strains used in this study, we conclude that weberviruses and their depolymerases show promise for development as therapeutic agents against Klebsiella spp
Kibble-Zurek scaling of the superfluid-supersolid transition in an elongated dipolar gas
Get PDFWe simulate interaction quenches crossing from a superfluid to a supersolid state in a dipolar quantum gas of Dy164 atoms, trapped in an elongated tube with periodic boundary conditions, via the extended Gross-Pitaevskii equation. A freeze-out time is observed through a delay in supersolid formation after crossing the critical point. We compute the density-density correlations at the freeze-out time and extract the frozen correlation length for the solid order. An analysis of the freeze-out time and correlation length versus the interaction quench rate allows us to extract universal exponents corresponding to the relaxation time and correlation length based on predictions of the Kibble-Zurek mechanism. Over several orders of magnitude, clear power-law scaling is observed for both the freeze-out time and the correlation length, and the corresponding exponents are compatible with predictions based on the excitation spectrum calculated via Bogoliubov theory. Defects due to independent local breaking of translational symmetry, contributing to globally incommensurate supersolid order, are identified, and their number at the freeze-out time is found to also scale as a power law. Our results support the hypothesis of a continuous transition whose universality class remains to be determined but appears to differ from that of the (1 + 1)-dimensional XY model
Resilient tree-planting strategies for carbon dioxide removal under compounding climate and economic uncertainties
Get PDFTo meet decarbonization targets, nations around the globe have made ambitious commitments to expand forested land. Operationalizing these commitments requires choosing a planting strategy: How many trees should be planted, of which species, and where? Given those choices must be made now but have long-term consequences, such decisions are plagued by uncertainty. For example, species that are well suited to present conditions may perform poorly under future climates, yet those future climates are themselves highly uncertain. Using the exemplar of the United Kingdom, a nation committed to achieving net zero emissions by midcentury, we quantify key uncertainties pertaining to coevolving climate and economic conditions and examine how modern methods of decision-making under uncertainty can advise on planting choices. Our analysis reveals that the best planting strategy assuming a “high-emissions” future is radically different to that for a future that remains on a “near-historic” path. Planting for the former while experiencing the latter results in substantial net costs to UK society. Assimilating uncertainty into decision-making identifies planting strategies that diversify risk and significantly reduce the probability of high-cost outcomes. Importantly, our research reveals that the scope for mitigating risk through choice of planting strategy is relatively limited. Despite this persistent risk, we find that tree planting remains a highly cost-effective carbon removal solution when compared to alternative technologies, even when those alternatives are assumed to be riskless
Cell signalling crosstalk between the epidermal growth factor receptor, β1-integrin and the c-Met receptor drives tunneling nanotube formation in lung adenocarcinoma
No full textNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths, with lung adenocarcinoma accounting for over half of all cases. Despite advances in targeted therapies, chemoresistance remains a major challenge, driven by complex alterations in receptor tyrosine kinases (RTK), integrin signalling, and intercellular communication within the tumour microenvironment (TME). Tunneling nanotubes (TNTs), which are F-actin-based structures facilitating long-distance transfer of oncogenic cargo, are an emerging mode of cell-to-cell communication implicated in cancer progression and chemoresistance, though their regulation remains poorly understood. The RTKs c-Met and EGFR, activated by hepatocyte growth factor (HGF) and epidermal growth factor (EGF) respectively, are frequently overexpressed in NSCLC and contribute to tumour aggressiveness. Both receptors independently crosstalk with β1-integrin, but whether they cooperate in a shared pathway to regulate TNT formation is unknown. Given the limitations of standard cancer therapies, alternative and combinatorial treatment strategies are also of clinical interest. This research investigated the signalling crosstalk between EGFR, c-Met, and β1-integrin in TNT formation in A5ti9 lung adenocarcinoma cells, while also exploring the broader implications of nanomedicine, and natural product-based therapies in cancer.
This research revealed a previously unexplored signalling crosstalk between the EGFR, β1-integrin and c-Met receptor in the formation of TNTs in A549 cells. Both HGF and EGF individually, as well as in combination, promoted TNT formation to a similar extent at higher concentrations; however, enhanced responses were observed with combined treatment at lower concentrations, suggesting crosstalk. The TNTs observed in this study were F-actin positive, with the presence of α-tubulin in thicker regions. Inhibitor studies identified that HGF/c-Met and EGF/EGFR signalling converged via the MAPK and PI3K pathways to drive TNT formation. Notably, dual inhibition of EGFR and c-Met was necessary to fully abrogate TNTs induced by simultaneous EGF+HGF stimulation. Furthermore, dual targeting of both receptors or their downstream MAPK/PI3K pathways resulted in a greater inhibition of TNT formation, suggesting potential compensatory signalling between the EGF/EGFR and HGF/c-Met axes. β1-integrin was also identified as a key mediator of TNT formation in response to both HGF, EGF, and EGF+HGF, with evidence of its role in linking receptor signalling to cytoskeletal remodelling via paxillin recruitment and Arp2/3 activation. The study further explored the impact of natural compounds and nanoparticles. Certain natural products demonstrated dual behaviour, where they exerted cytotoxic effects on cancer cells while an acetophenone-based fraction from the Knema membranifolia plant also induced TNT formation, highlighting the complexity of their cellular impact. Additionally, TNTs were shown to facilitate nanoparticle transfer, offering a compelling potential for their exploitation in drug delivery. In summary, this research has primarily characterised the crosstalk between EGFR, c-Met, and β1-integrin as a novel mechanism of TNT formation, which can have significant clinical implications in lung adenocarcinoma and overcoming chemoresistance via triple-targeting strategies. In addition, the identification of the modulatory effects of natural products and TNT-mediated transport of nanoparticles highlight the potential alternative role of TNTs in drug delivery