The radical left's turn towards civil society in Greece: One strategy, two paths

The Communist Party of Greece (KKE) and the Coalition of the Radical Left (SYRIZA) made remarkable ‘turns towards civil society’ over the last decade. It is argued that this was primarily a response aimed at strengthening their social legitimacy, which had reached its lowest point in the early 1990s. Differences in the way the two parties attempted to stabilise and engage their membership and re-establish links to trade unions and new social movements can be attributed to their distinct ideological and organisational legacies. Despite those differences, their respective linkage strategies were both successful until the game-changing 2012 Greek national elections, which brought about the remarkable rise of SYRIZA and the electoral demise of the KKE

JAK inhibitors: a potential treatment for JDM in the context of the role of interferon-driven pathology

Juvenile Idiopathic Inflammatory Myopathies (IIM) are a group of rare diseases that are heterogeneous in terms of pathology that can include proximal muscle weakness, associated skin changes and systemic involvement. Despite options for treatment, many patients continue to suffer resistant disease and lasting side-effects. Advances in the understanding of the immunopathology and genetics underlying IIM may specify new therapeutic targets, particularly where conventional treatment has not achieved a clinical response. An upregulated type I interferon signature is strongly associated with disease and could be a prime target for developing more specific therapeutics. There are multiple components of the IFN pathway that could be targeted for blockade therapy.Downstream of the cytokine receptor complexes are the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, which consists of JAK1-3, TYK2, and STAT1-6. Therapeutic inhibitors have been developed to target components of this pathway. Promising results have been observed in case studies reporting the use of the JAK inhibitors, Baricitinib, Tofacitinib and Ruxolitinib in the treatment of refractory Juvenile Dermatomyositis (JDM). There is still the question of safety and efficacy for the use of JAK inhibitors in JDM that need to be addressed by clinical trials. Here we review the future for the use of JAK inhibitors as a treatment for JDM

Treatment Strategies for Central Nervous System Effects in Primary and Secondary Haemophagocytic Lymphohistiocytosis in Children

Purpose of Review: This review presents an appraisal of current therapeutic options for the treatment of central nervous system haemophagocytic lymphohistiocytosis (CNS-HLH) in the context of systemic disease, as well as when CNS features occur in isolation. We present the reader with a diagnostic approach to CNS-HLH and commonly used treatment protocols. We discuss and evaluate newer treatments on the horizon. Recent Findings: Mortality is high in patients who do not undergo HSCT, and while larger studies are required to establish benefit in many treatments, a number of new treatments are currently being evaluated. Alemtuzumab is being used as a first-line treatment for CNS-HLH in a phase I/II multicentre prospective clinical trial as an alternative to traditional HLH-1994 and 2004 protocols. It has also been used successfully as a second-line agent for the treatment of isolated CNS-HLH that is refractory to standard treatment. Ruxolitinib and emapalumab are new immunotherapies that block the Janus kinase—Signal Transducer and Activator of Transcription (JAK-STAT) pathway that have shown efficacy in refractory HLH, including for CNS-HLH disease. Summary: Treatment of CNS-HLH often requires HLH-94 or 2004 protocols followed by haematopoietic stem cell transplantation (HSCT) to maintain remission, although relapse can occur, particularly with reduced intensity conditioning if donor chimerism falls. CNS features have been shown to improve or stabilise following HSCT in CNS-HLH in the context of systemic disease and in isolated CNS-HLH. Encouraging reports of early cohort studies suggest alemtuzumab and the Janus kinase (JAK) inhibitor ruxolitinib offer potential salvage therapy for relapsed and refractory CNS-HLH. Newer immunotherapies such as tocilizumab and natalizumab have been shown to be beneficial in sporadic cases. CNS-HLH due to primary gene defects may be amenable to gene therapy in the future

Nonlinear magnetoinductive transmission lines

Power transmission in one-dimensional nonlinear magnetic metamaterials driven at one end is investigated numerically and analytically in a wide frequency range. The nonlinear magnetic metamaterials are composed of varactor-loaded split-ring resonators which are coupled magnetically through their mutual inductances, forming thus a magnetoiductive transmission line. In the linear limit, significant power transmission along the array only appears for frequencies inside the linear magnetoinductive wave band. We present analytical, closed form solutions for the magnetoinductive waves transmitting the power in this regime, and their discrete frequency dispersion. When nonlinearity is important, more frequency bands with significant power transmission along the array may appear. In the equivalent circuit picture, the nonlinear magnetoiductive transmission line driven at one end by a relatively weak electromotive force, can be modeled by coupled resistive-inductive-capacitive (RLC) circuits with voltage-dependent capacitance. Extended numerical simulations reveal that power transmission along the array is also possible in other than the linear frequency bands, which are located close to the nonlinear resonances of a single nonlinear RLC circuit. Moreover, the effectiveness of power transmission for driving frequencies in the nonlinear bands is comparable to that in the linear band. Power transmission in the nonlinear bands occurs through the linear modes of the system, and it is closely related to the instability of a mode that is localized at the driven site.Comment: 11 pages, 11 figures, submitted to International Journal of Bifurcation and Chao

Moyamoya-like cerebrovascular disease in a child with a novel mutation in myosin heavy chain 11

Heterozygous mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a contractile protein of smooth muscle cells (SMC), have been described to cause thoracic aortic aneurysm or aortic dissection (TAAD) and patent ductus arteriosus (PDA).1 Herein we expand the phenotype associated with MYH11 mutations to include moyamoya-like cerebrovascular disease

Spectrum of Neuroradiologic Findings Associated with Monogenic Interferonopathies

The genetic interferonopathies are a heterogeneous group of disorders thought to be caused by the dysregulated expression of interferons and are now commonly considered in the differential diagnosis of children presenting with recurrent or persistent inflammatory phenotypes. With emerging therapeutic options, recognition of these disorders is increasingly important, and neuroimaging plays a vital role. In this article, we discuss the wide spectrum of neuroradiologic features associated with monogenic interferonopathies by reviewing the literature and illustrate these with cases from our institutions. These cases include intracerebral calcifications, white matter T2 hyperintensities, deep WM cysts, cerebral atrophy, large cerebral artery disease, bilateral striatal necrosis, and masslike lesions. A better understanding of the breadth of the neuroimaging phenotypes in conjunction with clinical and laboratory findings will enable earlier diagnosis and direct therapeutic strategies

Microparticle-mediated VZV propagation and endothelial activation: Mechanism of VZV vasculopathy

OBJECTIVE: Varicella zoster virus (VZV) can spread anterogradely and infect cerebral arteries causing VZV vasculopathy and arterial ischemic stroke. In this study, we tested the hypothesis that virus-infected cerebrovascular fibroblasts undergo phenotypic changes that promote vascular remodeling and facilitate virus transmission in an in vitro model of VZV vasculopathy. The aims of this project were therefore to examine the changes that virus-infected human brain adventitial vascular fibroblasts (HBVAFs) undergo in an in vitro model of VZV vasculopathy and to identify disease biomarkers relating to VZV-related vasculopathy. METHODS: HBVAFs were infected with VZV, and their ability to migrate, proliferate, transdifferentiate, and interact with endothelial cells was studied with flow cytometry. Microparticles (MPs) released from these cells were isolated and imaged with transmission electron microscopy, and their protein content was analyzed with mass spectrometry. Circulating MP profiles were also studied in children with VZV and non-VZV vasculopathy and compared with controls. RESULTS: VZV-infected HBVAFs transdifferentiated into myofibroblasts with enhanced proliferative and migratory capacity. Interaction of VZV-infected HBVAFs with endothelial cells resulted in endothelial dysfunction. These effects were, in part, mediated by the release of MPs from VZV-infected HBVAFs. These MPs contained VZV virions that could transmit VZV to neighboring cells, highlighting a novel model of VZV cell-to-cell viral dissemination. MPs positive for VZV were significantly higher in children with VZV-related vasculopathy compared to children with non-VZV vasculopathy (p = 0.01) and controls (p = 0.007). CONCLUSIONS: VZV-infected HBVAFs promote vascular remodeling and facilitate virus transmission. These effects were mediated by the release of apoptotic MPs that could transmit VZV infection to neighboring cells through a Trojan horse means of productive viral infection. VZV+ MPs may represent a disease biomarker worthy of further study

Memristive Effects in Oxygenated Amorphous Carbon Nanodevices

This is the author accepted manuscript. The final version is available from IOP Publishing via the DOI in this record.Computing with resistive-switching (memristive) memory devices has shown much recent progress and offers an attractive route to circumvent the von-Neumann bottleneck, i.e. the separation of processing and memory, which limits the performance of conventional computer architectures. Due to their good scalability and nanosecond switching speeds, carbon-based resistive-switching memory devices could play an important role in this respect. However, devices based on elemental carbon, such as tetrahedral amorphous carbon or t-aC, typically suffer from a low cycling endurance. A material that has proven to be capable of combining the advantages of elemental carbon-based memories with simple fabrication methods and good endurance performance for binary memory applications is oxygenated amorphous carbon, or a-COx. Here, we examine the memristive capabilities of nanoscale a-COx devices, in particular their ability to provide the multilevel and accumulation properties that underpin computing type applications. We show the successful operation of nanoscale a-COx memory cells for both the storage of multilevel states (here 3-level) and for the provision of an arithmetic accumulator. We implement a base-16, or hexadecimal, accumulator and show how such a device can carry out hexadecimal arithmetic and simultaneously store the computed result in the self-same a-COx cell, all using fast (sub-10 ns) and low-energy (sub-pJ) input pulses.This work was funded by the EU Research & Innovation project CareRAMM, grant no. 30998

Mediterranean diet and its components in relation to all-cause mortality: meta-analysis

The beneficial association of the Mediterranean diet (MedDiet) with longevity has been consistently demonstrated, but the associations of MedDiet components have not been accordingly evaluated. We performed an updated meta-analysis of prospective cohort studies published up to 31 December 2017, to quantify the association of adherence to MedDiet, expressed as an index/score (MDS) and of its components with all-cause mortality. We estimated summary relative risks (SRR) and 95 % CI using random effects models. On the basis of thirty studies (225 600 deaths), SRR for the study-specific highest/lowest and per 1sd MDS increment were 0\ub779 (95 % CI 0\ub777, 0\ub781, \u399 2=42 %, P-heterogeneity 0\ub702) and 0\ub792 (95 % CI 0\ub790, 0\ub794, \u399 2 56 %, P-heterogeneity <0\ub701), respectively. Inversely, statistically significant associations were evident in stratified analyses by country, MDS range and publication year, with some evidence for heterogeneity across countries overall (P-heterogeneity 0\ub7011), as well as across European countries (P=0\ub7018). Regarding MDS components, relatively stronger and statistically significant inverse associations were highlighted for moderate/none-excessive alcohol consumption (0\ub786, 95 % CI 0\ub777, 0\ub797) and for above/below-the-median consumptions of fruit (0\ub788, 95 % CI 0\ub783, 0\ub794) and vegetables (0\ub794, 95 % CI 0\ub789, 0\ub798), whereas a positive association was apparent for above/below-the-median intake of meat (1\ub707, 95 % CI 1\ub701, 1\ub713). Our meta-analyses confirm the inverse association of MedDiet with mortality and highlight the dietary components that influence mostly this association. Our results are important for better understanding the role of MedDiet in health and proposing dietary changes to effectively increase adherence to this healthy dietary pattern

Tackling Exascale Software Challenges in Molecular Dynamics Simulations with GROMACS

GROMACS is a widely used package for biomolecular simulation, and over the last two decades it has evolved from small-scale efficiency to advanced heterogeneous acceleration and multi-level parallelism targeting some of the largest supercomputers in the world. Here, we describe some of the ways we have been able to realize this through the use of parallelization on all levels, combined with a constant focus on absolute performance. Release 4.6 of GROMACS uses SIMD acceleration on a wide range of architectures, GPU offloading acceleration, and both OpenMP and MPI parallelism within and between nodes, respectively. The recent work on acceleration made it necessary to revisit the fundamental algorithms of molecular simulation, including the concept of neighborsearching, and we discuss the present and future challenges we see for exascale simulation - in particular a very fine-grained task parallelism. We also discuss the software management, code peer review and continuous integration testing required for a project of this complexity.Comment: EASC 2014 conference proceedin