Efficient real-time monitoring of an emerging influenza epidemic: how feasible?

A prompt public health response to a new epidemic relies on the ability to monitor and predict its evolution in real time as data accumulate. The 2009 A/H1N1 outbreak in the UK revealed pandemic data as noisy, contaminated, potentially biased, and originating from multiple sources. This seriously challenges the capacity for real-time monitoring. Here we assess the feasibility of real-time inference based on such data by constructing an analytic tool combining an age-stratified SEIR transmission model with various observation models describing the data generation mechanisms. As batches of data become available, a sequential Monte Carlo (SMC) algorithm is developed to synthesise multiple imperfect data streams, iterate epidemic inferences and assess model adequacy amidst a rapidly evolving epidemic environment, substantially reducing computation time in comparison to standard MCMC, to ensure timely delivery of real-time epidemic assessments. In application to simulated data designed to mimic the 2009 A/H1N1 epidemic, SMC is shown to have additional benefits in terms of assessing predictive performance and coping with parameter non-identifiability.MRC, NIH

Efficient real-time monitoring of an emerging influenza pandemic: How feasible?

A prompt public health response to a new epidemic relies on the ability to monitor and predict its evolution in real time as data accumulate. The 2009 A/H1N1 outbreak in the UK revealed pandemic data as noisy, contaminated, potentially biased and originating from multiple sources. This seriously challenges the capacity for real-time monitoring. Here, we assess the feasibility of real-time inference based on such data by constructing an analytic tool combining an age-stratified SEIR transmission model with various observation models describing the data generation mechanisms. As batches of data become available, a sequential Monte Carlo (SMC) algorithm is developed to synthesise multiple imperfect data streams, iterate epidemic inferences and assess model adequacy amidst a rapidly evolving epidemic environment, substantially reducing computation time in comparison to standard MCMC, to ensure timely delivery of real-time epidemic assessments. In application to simulated data designed to mimic the 2009 A/H1N1 epidemic, SMC is shown to have additional benefits in terms of assessing predictive performance and coping with parameter nonidentifiability

Doping-dependent study of the periodic Anderson model in three dimensions

We study a simple model for $f$-electron systems, the three-dimensional periodic Anderson model, in which localized $f$ states hybridize with neighboring $d$ states. The $f$ states have a strong on-site repulsion which suppresses the double occupancy and can lead to the formation of a Mott-Hubbard insulator. When the hybridization between the $f$ and $d$ states increases, the effects of these strong electron correlations gradually diminish, giving rise to interesting phenomena on the way. We use the exact quantum Monte-Carlo, approximate diagrammatic fluctuation-exchange approximation, and mean-field Hartree-Fock methods to calculate the local moment, entropy, antiferromagnetic structure factor, singlet-correlator, and internal energy as a function of the $f-d$ hybridization for various dopings. Finally, we discuss the relevance of this work to the volume-collapse phenomenon experimentally observed in f-electron systems.Comment: 12 pages, 8 figure

Genes in the postgenomic era

We outline three very different concepts of the gene - 'instrumental', 'nominal', and 'postgenomic'. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists in a wide range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype

A justification of whistleblowing

Penultimate version accepted for publicationWhistleblowing is the act of disclosing information from a public or private organization in order to reveal cases of corruption that are of immediate or potential danger to the public. Blowing the whistle involves personal risk, especially when legal protection is absent, and charges of betrayal, which often come in the form of legal prosecution under treason laws. In this article we argue that whistleblowing is justified when disclosures are made with the proper intent and fulfill specific communicative constraints in addressing issues of public interest. Three communicative constraints of informativeness, truthfulness and evidence are discussed in this regard. We develop a ‘harm test’ to assess the intent for disclosures, concluding that it is not sufficient for justification. Along with the proper intent, a successful act of whistleblowing should provide information that serves the public interest. Taking cognizance of the varied conceptions of public interest, we present an account of public interest that fits the framework of whistleblowing disclosures. In particular, we argue that whistleblowing is justified inter alia when the information it conveys is of a presumptive interest for a public insofar as it reveals an instance of injustice or violation of a civil or political right done against and unbeknown to some members of a polity.Project: ‘Change of Direction. Fostering Whistleblowing in the Fight against Corruption’ co-funded by the Internal Security Fund of the European Union (Grant Agreement Number: HOME/2014/ISFP/AG/EFCE/7233); SFRH/BPD/108669/2015info:eu-repo/semantics/publishedVersio

Economic crisis and the construction of a neo-liberal regulatory regime in Korea

A consistent theme of the literature on the ontology of the 1997 South Korean crisis is the key role played by regulatory failures and the growing weakness of the state. This paper seeks to briefly highlight both the insights and the limitations of this approach to understanding the crisis. Having done so, we shall set out the argument that the crisis created an opportunity for reformist Korean élites to advance their longstanding, but previously frustrated, project to create a comprehensive unambiguously neo-liberal regulatory regime. This paper will also seek to highlight the implications of our reading of the development of the Korean political economy for broader debates on economic liberalisation, crisis and the future of the developmental state

‘Dominant ethnicity’ and the ‘ethnic-civic’ dichotomy in the work of A. D. Smith

This article considers the way in which the work of Anthony Smith has helped to structure debates surrounding the role of ethnicity in present-day nations. Two major lines of enquiry are evident here. First, the contemporary role of dominant ethnic groups within 'their' nations and second, the interplay between ethnic and civic elements in nationalist argument. The two processes are related, but maintain elements of distinctiveness. Smith's major contribution to the dominant ethnicity debate has been to disembed ethnicity from the ideologically-charged and/or anglo-centric discourse of ethnic relations and to place it in historical context, thereby opening up space for dominant group ethnicity to be considered as a distinct phenomenon. This said, Smith's work does not adequately account for the vicissitudes of dominant ethnicity in the contemporary West. Building on the classical works of Hans Kohn and Friedrich Meinecke, Anthony Smith has also made a seminal contribution to the debate on civic and ethnic forms of national identity and nationalist ideology. As well as freeing this debate from the strong normative overtones which it has often carried, he has continued to insist that the terms civic and ethnic should be treated as an ideal-typical distinction rather than a scheme of classification

Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein

Publisher Copyright: © 2022 National Academy of Sciences. All rights reserved.Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available coronavirus disease 2019 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors, which block formation of the so-called heptad repeat 1 and 2 (HR1HR2) six-helix bundle of the SARS-CoV-2 spike (S) protein and thus interfere with viral membrane fusion. We performed structural studies of the HR1HR2 bundle, revealing an extended, well-folded N-terminal region of HR2 that interacts with the HR1 triple helix. Based on this structure, we designed an extended HR2 peptide that achieves single-digit nanomolar inhibition of SARS-CoV-2 in cell-based and virus-based assays without the need for modifications such as lipidation or chemical stapling. The peptide also strongly inhibits all major SARS-CoV-2 variants to date. This extended peptide is ∼100-fold more potent than all previously published short, unmodified HR2 peptides, and it has a very long inhibition lifetime after washout in virus infection assays, suggesting that it targets a prehairpin intermediate of the SARS-CoV-2 S protein. Together, these results suggest that regions outside the HR2 helical region may offer new opportunities for potent peptide-derived therapeutics for SARS-CoV-2 and its variants, and even more distantly related viruses, and provide further support for the prehairpin intermediate of the S protein.Peer reviewe

Magnetic Moment Collapse-Driven Mott Transition in MnO

The metal-insulator transition in correlated electron systems, where electron states transform from itinerant to localized, has been one of the central themes of condensed matter physics for more than half a century. The persistence of this question has been a consequence both of the intricacy of the fundamental issues and the growing recognition of the complexities that arise in real materials, even when strong repulsive interactions play the primary role. The initial concept of Mott was based on the relative importance of kinetic hopping (measured by the bandwidth) and on-site repulsion of electrons. Real materials, however, have many additional degrees of freedom that, as is recently attracting note, give rise to a rich variety of scenarios for a ``Mott transition.'' Here we report results for the classic correlated insulator MnO which reproduce a simultaneous moment collapse, volume collapse, and metallization transition near the observed pressure, and identify the mechanism as collapse of the magnetic moment due to increase of crystal field splitting, rather than to variation in the bandwidth.Comment: 18 pages, 5 figur

The CUAVA-2 CubeSat: A Second Attempt to Fly the Remote Sensing, Space Weather Study and Earth Observation Instruments

This paper presents the 6U CubeSat mission conducted by the ARC Training Centre for CubeSats, UAVs, and their Applications (CUAVA) at the University of Sydney. CUAVA-2, the second CubeSat project following the CUAVA-1 mission, builds upon lessons learned from its predecessor. CUAVA-1, the first satellite launched by CUAVA, carried first-generation payloads for earth observation goals and technology demonstrations but experienced communication difficulties. A fault root analysis was performed on CUAVA-1 to inform the design of CUAVA-2. The CUAVA-2 satellite incorporates a hyperspectral imager for applications in agriculture, forestry, coastal and marine environments, urban areas, water hazard assessment, and mineral exploration. It also includes a GPS reflectometry payload for remote sea state determination, as well as secondary payloads for technology demonstration and space weather study. This paper discusses the fault analysis findings, lessons learned, and design inputs from CUAVA-1, showcasing their integration into the CUAVA-2 satellite, which is scheduled for launch in February 2024