A European mechanism for sovereign debt crisis resolution: a proposal

This Bruegel Blueprint argues that Europe should take the lead in defining a solution to the problem of excessive public debts and create a European Crisis Resolution Mechanism (ECRM).The authors, Francois Gianviti, Anne O. Krueger, Jean Pisani-Ferry, André Sapir and Jürgen von Hagen, present the rationale for such a mechanism in the euro area and details of how an ECRM would work. The ECRM would be a permanent tool to deal with sovereign debt crises in an effective and predictable way.

Making the Internet of Things More Reliable Thanks to Dynamic Access Control

While the Internet-of-Things (IoT) infrastructure is rapidly growing, the performance and correctness of such systems becomes more and more critical. Together with flexibility and interoperability, trustworthiness related aspects, including security, privacy, resilience and robustness, are challenging goals faced by the next generation of IoT systems. In this chapter, we propose approaches for IoT tailored access control mechanisms that ensure data and services protection against unauthorized use, with the aim of improving IoT system trustworthiness and lowering the risks of massive-scale IoT-driven cyber-attacks or incidents.acceptedVersio

AFM imaging of functionalized double-walled carbon nanotubes

We present a comparative study of several non-covalent approaches to disperse, debundle and noncovalently functionalize double-walled carbon nanotubes (DWNTs). We investigated the ability of bovine serum albumin (BSA), phospholipids grafted onto amine-terminated polyethylene glycol (PLPEG2000-NH2), as well as a combination thereof, to coat purified DWNTs. Topographical imaging with the atomic force microscope (AFM) was used to assess the coating of individual DWNTs and the degree of debundling and dispersion. Topographical images showed that functionalized DWNTs are better separated and less aggregated than pristine DWNTs and that the different coating methods differ in their abilities to successfully debundle and disperse DWNTs. Height profiles indicated an increase in the diameter of DWNTs depending on the functionalization method and revealed adsorption of single molecules onto the nanotubes. Biofunctionalization of the DWNT surface was achieved by coating DWNTs with biotinylated BSA, providing for biospecific binding of streptavidin in a simple incubation step. Finally, biotin-BSA-functionalized DWNTs were immobilized on an avidin layer via the specific avidin–biotin interaction

The failure of global public health governance : a forensic analysis

Published online : 17 February 2022The emergence of the Omicron variant in November 2021 was a stark reminder of the high overall cost of the persistence globally of extremely unequal access to vaccines and treatments. What are the reasons for these failures of global collective action

Elevated levels of Endothelial cell-derived microparticles following short-term withdrawal of continuous positive airway pressure in patients with obstructive sleep apnea: Data from a randomized controlled trial

Background: Obstructive sleep apnea has been associated with impaired endothelial function; however, the mechanisms underlying this association are not completely understood. Cell-derived microparticles may provide a link between obstructive sleep apnea and endothelial dysfunction. Objectives: This randomized controlled trial aimed to examine the effect of a 2-week withdrawal of continuous positive airway pressure (CPAP) therapy on levels of circulating microparticles. Methods: Forty-one obstructive sleep apnea patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks. Results: CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels of CD62E+ endothelium-derived microparticles increased significantly in the CPAP withdrawal group compared to the continuing therapeutic CPAP group (median difference in change +32.4 per µl; 95% CI +7.3 to +64.1 per µl, p = 0.010). CPAP withdrawal was not associated with a statistically significant increase in granulocyte, leukocyte, and platelet-derived microparticles when compared with therapeutic CPAP. Conclusions: Short-term withdrawal of CPAP therapy leads to a significant increase in endothelium-derived microparticles, suggesting that microparticle formation may be causally linked to obstructive sleep apnea and may promote endothelial activation

A Single Residue Exchange Within a Viral CTL Epitope Alters Proteasome-Mediated Degradation Resulting in Lack of Antigen Presentation

AbstractCTL epitope (KSPWFTTL) encoded by AKV/MCF type of murine leukemia virus (MuLV) differs from the sequence in Friend/Moloney/Rauscher (FMR) type in one residue (RSPWFTTL). CTL experiments indicated defective processing of the FMR peptide in tumor cells. Proteasome-mediated digestion of AKV/MCF-type 26-mer peptides resulted in the early generation and higher levels of epitope-containing fragments than digestion of FMR-type peptides, explained by prominent cleavage next to R in the FMR sequence. The fragments were identified as 10- and 11-mer peptides and were efficiently translocated by TAP. The naturally presented AKV/MCF peptide is the 8-mer, indicating ER peptide trimming. In conclusion, a single residue exchange can cause CTL epitope destruction by specific proteasomal cleavage

Case report: Continuous infusions of ceftazidime-avibactam and aztreonam in combination through elastomeric infusors for 12 weeks for the treatment of bone and joint infections due to metallo-β-lactamase producing Enterobacterales

Among carbapenem-resistant Enterobacterales, metallo-beta-lactamase producing strains represent a growing therapeutic challenge. While the association of aztreonam and ceftazidime-avibactam has been investigated in recent years for the treatment of infections involving these strains, little to no clinical data support the use of this association for the treatment of bone and joint infections. We report two cases of complex bone and joint infections involving metallo-beta-lactamase-producing Enterobacterales, successfully treated at our referral center with aztreonam and ceftazidime-avibactam for 12 weeks in continuous infusions through elastomeric infusors

Three dimensional in vitro models of cancer: Bioprinting multilineage glioblastoma models

International audienceThree dimensional (3D) bioprinting of multiple cell types within optimised extracellular matrices has the potential to more closely model the 3D environment of human physiology and disease than current alternatives. In this study, we used a multi-nozzle extrusion bioprinter to establish models of glioblastoma made up of cancer and stromal cells printed within matrices comprised of alginate modified with RGDS cell adhesion peptides, hyaluronic acid and collagen-1. Methods were developed using U87MG glioblastoma cells and MM6 monocyte/macrophages, whilst more disease relevant constructs contained glioblastoma stem cells (GSCs), co-printed with glioma associated stromal cells (GASCs) and microglia. Printing parameters were optimised to promote cell-cell interaction, avoiding the 'caging in' of cells due to overly dense cross-linking. Such printing had a negligible effect on cell viability, and cells retained robust metabolic activity and proliferation. Alginate gels allowed the rapid recovery of printed cell protein and RNA, and fluorescent reporters provided analysis of protein kinase activation at the single cell level within printed constructs. GSCs showed more resistance to chemotherapeutic drugs in 3D printed tumour constructs compared to 2D monolayer cultures, reflecting the clinical situation. In summary, a novel 3D bioprinting strategy is developed which allows control over the spatial organisation of tumour constructs for pre-clinical drug sensitivity testing and studies of the tumour microenvironment

Experimental evaluation of the pseudotime principle for nonisothermal polymer flows

We have applied a series of start-up of uniaxial extensions to very high strain followed by stress relaxation. A potential temperature change was applied during the stress relaxation. We used two thermorheological simple polymers; a linear polystyrene and a branched low density polyethylene. Experiments performed with temperature changes during the stress relaxation were shown to be identical with isothermal ones in the “pseudotime”, within the accuracy of the experiments. This verifies that the pseudotime approach seems to be the general basis for nonisothermal microstructural modeling for flow of polymers. The pseudotime is given as ξ(t) = ∫to 1/aT(T(t1))dT1, where aT are the well established time-temperature superposition shift factors, calculated from the past temperatures (at time t0) in a particle path

High-sensitivity troponin and the application of risk stratification thresholds in patients with suspected acute coronary syndrome

Background: Guidelines acknowledge the emerging role of high-sensitivity cardiac troponin (hs-cTnl) for risk stratification and the early rule-out of myocardial infarction, but multiple thresholds have been described. We evaluate the safety and effectiveness of risk stratification thresholds in patients with suspected acute coronary syndrome. Methods: Consecutive patients with suspected acute coronary syndrome (n=48 282) were enrolled in a multicenter trial across 10 hospitals in Scotland. In a prespecified secondary and observational analysis, we compared the performance of the limit of detection (<2 ng/L) and an optimized risk stratification threshold (<5 ng/L) using the Abbott high-sensitivity troponin I assay. Patients with myocardial injury at presentation, with ≤2 hours of symptoms or with ST-segment elevation myocardial infarction were excluded. The negative predictive value was determined in all patients and in subgroups for a primary outcome of myocardial infarction or cardiac death within 30 days. The secondary outcome was myocardial infarction or cardiac death at 12 months, with risk modeled using logistic regression adjusted for age and sex. Results: In total, 32 837 consecutive patients (61±17 years, 47% female) were included, of whom 23 260 (71%) and 12,716 (39%) had hs-cTnl concentrations of <5 ng/L and <2 ng/L at presentation. The negative predictive value for the primary outcome was 99.8% (95% CI, 99.7%–99.8%) and 99.9% (95% CI, 99.8%–99.9%) in those with hs-cTnl concentrations of <5 ng/L and <2 ng/L, respectively. At both thresholds, the negative predictive value was consistent in men and women and across all age groups, although the proportion of patients identified as low risk fell with increasing age. Compared with patients with hs-cTnl concentrations of ≥5 ng/L but <99th centile, the risk of myocardial infarction or cardiac death at 12 months was 77% lower in those <5 ng/L (5.3% vs 0.7%; adjusted odds ratio, 0.23 [95% CI, 0.19–0.28]) and 80% lower in those <2 ng/L (5.3% vs 0.3%; adjusted odds ratio, 0.20 [95% CI, 0.14–0.29]). Conclusions: Use of risk stratification thresholds for hs-cTnl identify patients with suspected acute coronary syndrome and at least 2 hours of symptoms as low risk at presentation irrespective of age and sex