FMDV replicons encoding green fluorescent protein are replication competent

The study of replication of viruses that require high bio-secure facilities can be accomplished with less stringent containment using non-infectious 'replicon' systems. The FMDV replicon system (pT7rep) reported by Mclnerney et al. (2000) was modified by the replacement of sequences encoding chloramphenicol acetyl-transferase (CAT) with those encoding a functional L proteinase (Lpro) linked to a bi-functional fluorescent/antibiotic resistance fusion protein (green fluorescent protein/puromycin resistance, [GFP-PAC]). Cells were transfected with replicon-derived transcript RNA and GFP fluorescence quantified. Replication of transcript RNAs was readily detected by fluorescence, whilst the signal from replication-incompetent forms of the genome was >2-fold lower. Surprisingly, a form of the replicon lacking the Lpro showed a significantly stronger fluorescence signal, but appeared with slightly delayed kinetics. Replication can, therefore, be quantified simply by live-cell imaging and image analyses, providing a rapid and facile alternative to RT-qPCR or CAT assays

The meta-crisis of secular capitalism

The current global economic crisis concerns the way in which contemporary capitalism has turned to financialisation as a double cure for both a falling rate of profit and a deficiency of demand. Although this turning is by no means unprecedented, policies of financialisation have depressed demand (in part as a result of the long-term stagnation of average wages) while at the same time not proving adequate to restore profits and growth. This paper argues that the current crisis is less the ‘normal’ one that has to do with a constitutive need to balance growth of abstract wealth with demand for concrete commodities. Rather, it marks a meta-crisis of capitalism that is to do with the difficulties of sustaining abstract growth as such. This meta-crisis is the tendency at once to abstract from the real economy of productive activities and to reduce everything to its bare materiality. By contrast with a market economy that binds material value to symbolic meaning, a capitalist economy tends to separate matter from symbol and reduce materiality to calculable numbers representing ‘wealth’. Such a conception of wealth rests on the aggregation of abstract numbers that cuts out all the relational goods and the ‘commons’ on which shared prosperity depends

Informing the development of Australia's national eating disorders research and translation strategy : a rapid review methodology

Background Eating disorders (EDs) are highly complex mental illnesses associated with significant medical complications. There are currently knowledge gaps in research relating to the epidemiology, aetiology, treatment, burden, and outcomes of eating disorders. To clearly identify and begin addressing the major deficits in the scientific, medical, and clinical understanding of these mental illnesses, the Australian Government Department of Health in 2019 funded the InsideOut Institute (IOI) to develop the Australian Eating Disorder Research and Translation Strategy, the primary aim of which was to identify priorities and targets for building research capacity and outputs. A series of rapid reviews (RR) were conducted to map the current state of knowledge, identify evidence gaps, and inform development of the national research strategy. Published peer-reviewed literature on DSM-5 listed EDs, across eight knowledge domains was reviewed: (1) population, prevalence, disease burden, Quality of Life in Western developed countries; (2) risk factors; (3) co-occurring conditions and medical complications; (4) screening and diagnosis; (5) prevention and early intervention; (6) psychotherapies and relapse prevention; (7) models of care; (8) pharmacotherapies, alternative and adjunctive therapies; and (9) outcomes (including mortality). While RRs are systematic in nature, they are distinct from systematic reviews in their aim to gather evidence in a timely manner to support decision-making on urgent or high-priority health concerns at the national level. Results Three medical science databases were searched as the primary source of literature for the RRs: Science Direct, PubMed and OVID (Medline). The search was completed on 31st May 2021 (spanning January 2009-May 2021). At writing, a total of 1,320 articles met eligibility criteria and were included in the final review. Conclusions For each RR, the evidence has been organised to review the knowledge area and identify gaps for further research and investment. The series of RRs (published separately within the current series) are designed to support the development of research and translation practice in the field of EDs. They highlight areas for investment and investigation, and provide researchers, service planners and providers, and research funders rapid access to quality current evidence, which has been synthesised and organised to assist decision-making

Watson Health: A New Approach to Population Health and Research

Background/Aims: The population health management movement requires key strategies be employed by some of the nation’s largest and most prestigious physician groups and health systems (most included in the HCSRN) to automate the management of their populations and improve health outcomes. Watson Health represents a health information technology (IT) and big data insights approach to enhance patient experience, management and outcomes. We bring together common data sources for evidence that is consistent across platforms, including payers, providers and pharmaceuticals. Methods: Utilizing advanced analytics and IT structures, Watson Health data infrastructure management allows physicians and researchers to gain insights from existing data assets. Built on top of the enterprise data warehouse, interface strategies such as Explorys and Phytel have been built and instituted at several organizations. We have established trusted data for all stakeholders in the health care ecosystem to provide evidence that is needed for the collaboration between all aspects of health management and life sciences development. Results: With the Explorys and Phytel tools, we were able to build tools to assist physicians and other care-team members. Data from registries, other providers, pharmacies, claims and laboratory sources was used to identify gaps in care that needed to be filled. Identification of specific patient populations can easily be identified for care alerts, clinical trial eligibility, research enrollment or follow-up at a huge time savings for the care team and research staff. Conclusion: To create a sustainable health care system that provides affordable, high-quality health care to all, a population health management approach like that offered by Watson Health needs to be adopted by physicians and outcomes validated by health care research. Current electronic health records lack many of the features required to improve population health; therefore, new technologies are important to reach the overarching goal to improve population health

Geometrical Constraints of Observing Very High Energy Earth-Skimming Neutrinos from Space

International audienceThe detection of very-high-energy (VHE) neutrinos (Eν  10 PeV) is a challenge that future generations of experiments are being designed and constructed to address. One promising method relies on using the Earth as a neutrino target for indirect detection of skimming tau neutrinos interacting within the Earth and producing tau leptons that are able to escape and decay in the atmosphere. The tau decay produces upward-moving Extensive Air Showers (EASs). A space-based or suborbital instrument observing the ground near the Earth limb can search for the beamed Cherenkov signal produced by the up-going EAS resulting from the tau-lepton decay. In this paper, we derive the geometrical constraints for such an observation in general and for the specific case of the Probe Of Extreme Multi-Messenger Astrophysics (POEMMA) mission currently under study, focusing on the Cherenkov signal detection. We show that, using reasonable orbital parameters, POEMMA can achieve full-sky coverage to search for potential neutrino sources over the length of its mission. We also show that follow-up of a transient Target-of-Opportunity (ToO), such as a flaring source, can be achieved within an orbit time scale depending on the source location on the celestial sphere and its relative position with respect to the Sun and the Moon

Design and Testing of High Power, Repetitively Pulsed Solid-State Closing Switches

Repetitively pulsed closing switches are often required in high-power physics experiments. Traditionally, ignitrons have been used for these applications. There are reasons why ignitrons have undesirable features, such as the high trigger current which causes electromagnetic interference, the arc instability and environmental concern with the mercury used in the switches. With the development of ever increasing power rating of solid-state switches, in particular thyristors, the designer has the tools to replace ignitrons with solid-state devices. Using as an example a recently designed and tested 10 kV, 80 kA high-power switch, the design philosophy for repetitively pulsed switches is developed. The parameters which impose the greatest challenge on the device, such as di/dt, temperature rise and reverse blocking voltage are investigated with respect to their capability when operating in the pulsed mode. Starting with the available device data sheet information and published results of the dependency of the number of life cycles as a function of the device temperature, it is shown how the overload capability of a device for short term pulsed applications can be exploited. The detailed design of a 2 Hz, 10{sup 8} cycle, 12.5 kV, 80 kA, 3 ms switch, with a short circuit capability of 250 kA, is presented. The paper concludes with a short summary about device limits in voltage, current amplitude and pulse length ratings for repetitively pulsed switches using available thyristors