Iclaprim reduces the incidence and severity of Staphylococcus aureus-induced septic arthritis in a murine model

Staphylococcus aureus is the most common non-gonococcal aetiology of septic arthritis. The efficacy of iclaprim against S. aureus LS-1, a clinical strain identified from a patient with septic arthritis, was studied in MF1 mice to evaluate the activity of iclaprim, which is in clinical development, in preventing joint infections. Iclaprim (2.5–80 mg kg− 1) administered as a single dose via the tail vein reduced the incidence of S. aureus septic arthritis and mortality in an experimental murine model of septic arthritis

Development of large radii half-wave plates for CMB satellite missions

The successful European Space Agency (ESA) Planck mission has mapped the Cosmic Microwave Background (CMB) temperature anisotropy with unprecedented accuracy. However, Planck was not designed to detect the polarised components of the CMB with comparable precision. The BICEP2 collaboration has recently reported the first detection of the B-mode polarisation. ESA is funding the development of critical enabling technologies associated with B-mode polarisation detection, one of these being large diameter half-wave plates. We compare different polarisation modulators and discuss their respective trade-offs in terms of manufacturing, RF performance and thermo-mechanical properties. We then select the most appropriate solution for future satellite missions, optimized for the detection of B-modes.Comment: 16 page

Histone deacetylase 4 is crucial for proper skeletal muscle development and disease

Epigenetics plays a pivotal role in modulating gene response to physiological or pathological stimuli. Histone Deacetylase inhibitors (HDACi) have been used in the treatment of various cancers1, are ef-fective in several animal models of neurodegenerative diseases, including amyotrophic lateral scle-rosis (ALS), and are currently in clinical trial to promote muscle repair in muscular dystrophies2. However, long-term use of pan-HDAC inhibitors is not tolerated3. The assignment of distinct biologi-cal functions to individual HDACs in skeletal muscle is a prerequisite to improve the efficacy of pharmacological treatments based on HDACi. HDAC4 is a member of class II HDACs that mediates many cellular responses. Clinical reports suggest that inhibition of HDAC4 can be beneficial to cancer cachexia, dystrophic or ALS patients. All the above conditions are characterized by progressive mus-cle wasting and up-regulation of HDAC4 expression in skeletal muscle, suggesting a potential role for this protein in regulating these diseases. To study the role of HDAC4 with a genetic approach, we generated several models of muscle disease in mice lacking HDAC4 in skeletal muscle: cancer ca-chexia, by implanting Lewis lung carcinoma (LLC), muscular dystrophy, by using mdx mice, or ALS, by using SODG93A mice. Lack of HDAC4 worsens skeletal muscle atrophy induced by both LLC and ALS, demonstrated by a reduction in muscle mass and myofibers size. Conversely, dystrophic mice lacking HDAC4 in skeletal muscle show an increased number of necrotic myofibers and run less efficiently than mdx mice. The aggravation of the dystrophic phenotype may be partially due to the impairment in skeletal muscle regeneration observed in mice lacking HDAC4 in skeletal muscle. Our results indi-cate that HDAC4 is necessary for maintaining skeletal muscle homeostasis and function. Current studies aim to investigate the molecular mechanisms underlying the role of HDAC4 in skeletal mus-cle maintenance in response to cancer cachexia, ALS or muscular dystrophy

HDAC4 is necessary for satellite cell differentiation and muscle regeneration

In response to injury, skeletal muscle exhibits high capacity to regenerate and epigenetics controls multiple steps of this process (Giordani et al., 2013). It has been demonstrated in vitro that completion of muscle differentiation requires shuttling of histone deacetylase 4 (HDAC4), a member of class IIa HDACs, from the nucleus to the cytoplasm and consequent activation of MEF2-dependent differentiation genes (McKinsey et al., 2000). In vivo, HDAC4 expression is up-regulated in skeletal muscle upon injury, suggesting a role for this protein in muscle regeneratio

Long-term safety and effectiveness of canakinumab therapy in patients with cryopyrin-associated periodic syndrome: results from the β-Confident Registry.

OBJECTIVE: To report the long-term safety and effectiveness of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID), in a real-world setting. METHODS: From December 2009 to December 2015, the β-Confident Registry prospectively enrolled patients with CAPS and non-CAPS conditions who received canakinumab per routine care and were prospectively followed for up to 6 years. The registry protocol did not mandate specific visits or procedures; however, all observed adverse events (AEs) and serious adverse events (SAEs) had to be recorded. Canakinumab effectiveness was evaluated by Physician's Global Assessment (PGA). RESULTS: Of 288 patients enrolled, 3 were excluded due to missing informed consent. Among the remaining 285 patients, 243 (85.3%) were patients with CAPS and 42 (14.7%) had atypical CAPS (6.3%) or other conditions (8.4%). The median age was 26.6 years. Based on PGA, 58 of 123 (47.2%) patients with CAPS had no disease activity at 48 months, and 65 of 123 (52.8%) experienced mild/moderate disease activity at 48 months. Among CAPS phenotypes, AE incidence rates per 100 patient-years were lowest for FCAS (73.1; 95% CI 60.3 to 87.8) compared with those with MWS (105.0; 95% CI 97.2 to 113.2) or NOMID (104.6; 95% CI 86.6 to 125.2). One hundred twenty-eight SAEs were reported in 68 patients with CAPS (incidence rate/100 patient-years, 14.0; 95% CI 11.6 to 16.6). One death (metastatic rectal adenocarcinoma in a patient with MWS) was reported. CONCLUSIONS: The response to canakinumab was sustained for up to 6 years. Canakinumab demonstrated a favourable safety profile over long-term treatment in patients with CAPS. TRIAL REGISTRATION NUMBER: NCT01213641

SOLE Project – Demonstration of a Multistatic and Multiband Coherent Radar Network

The aim of the NATO-SPS SOLE project is demonstrating the feasibility and the high performance of a radar network thanks to photonics. Indeed, the coherence offered by photonics makes the proposed distributed radar system capable of an efficient implementation of MIMO processing and ISAR imaging, enhancing the performance in terms of resolution and precision. The advantage of a fully coherent, multistatic radar system here is experimentally proven by a 5-time cross-range resolution enhancement thanks to MIMO processing, and in an efficient focusing in ISAR imaging

The evolution of the footwall to the Ronda subcontinental mantle peridotites: insights from the Nieves Unit (western Betic Cordillera)

Strongly heterogeneous deformation and extreme metamorphic gradients characterize the dominantly carbonate Nieves Unit in the footwall to the Ronda mantle extrusion wedge in the western Betic Cordillera. A well-developed foliation and mineral lineation, together with isoclinal intrafolial folds, occur in silicate-bearing, calcite or dolomite marbles within a c. 1.5 km thick metamorphic aureole underlying the peridotites. For the inferred maximum pressure of 300 MPa, petrological investigations allow us to define temperature ranges for the main zones of the metamorphic aureole: >510 °C (probably c. 700 °C) for the forsterite zone; 510–430 °C for the diopside zone; 430–360 °C for the tremolite zone; 360–330 °C for the phlogopite zone. Field structural analysis integrated with petrological, microstructural and electron backscatter diffraction textural data document large finite strains consistent with general shear within the metamorphic aureole, associated with NW-directed thrusting of the peridotites. On the other hand, post-kinematic silicate growth suggests that heat diffusion from the high-temperature peridotites continued after the final emplacement of the Ronda mantle extrusion wedge, leading to final zoning of the metamorphic aureole and to local partial annealing of calcite marble textures, particularly in the highest-temperature zone of the thermally softened footwall carbonates. Following substantial cooling, renewed crustal shortening affected the whole Nieves Unit, resulting in widespread development of NE–SW-trending meso-scale folds

In-Vivo Expansion of T Regulatory Cells by Rapamycin in a Calcineurin-Inhibitor Free GVHD Prophylaxis in Unmanipulated Haploidentical Stem Cell Transplantation (SCT)

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