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Quantum illumination protocols can be implemented to improve imaging performance in the low photon flux regime even in the presence of both background light and sensor noise. However, the extent to which this noise can be rejected is limited by the rate of accidental correlations resulting from the detection of photon or noise events that are not quantum-correlated. Here we present an improved protocol that rejects up to ≳ 99.9 % of background light and sensor noise in the low photon flux regime, improving upon our previous results by an order of magnitude. This improvement, which requires no information regarding the scene or noise statistics, will enable extremely low light quantum imaging techniques to be applied in environments previously thought difficult and be an important addition to the development of covert imaging, quantum microscopes, and quantum LIDAR. [ABSTRACT FROM AUTHOR]

• This EHA-ESMO Clinical Practice Guideline provides key recommendations on the management of multiple myeloma. • Authorship includes a multidisciplinary group of experts from different institutions and countries in Europe. • Key treatment recommendations are provided for both newly diagnosed myeloma patients and patients with relapsed/refractory disease. • Recommendations for the treatment of plasma cell leukaemia, solitary plasmacytoma and smouldering myeloma are also provided. • Key recommendations for myeloma complications, including bone disease and renal impairment, are included. [ABSTRACT FROM AUTHOR]

The integrated commissioning of the tungsten (W) environment in steady-state tokamak (WEST) was started with the superconducting magnet cool-down and completed one year after by the injection of 2.5 MW of additional power. It consisted of several steps: local system commissioning, integrated commissioning without plasma, and first plasma operation. This article reviews these WEST commissioning phases and highlights the experiences and the lessons learned. The magnet cooling down operation was initiated in late September 2016. The vacuum vessel was pumped out three weeks before the first plasma. The impregnation and curing of the two in-vessel divertor coils was performed at 180 °C during two days contributing to the baking of the vacuum vessel. In the meanwhile, rehearsal sessions for testing the CODAC systems were organized every month. The toroidal, poloidal, and divertor field coils were energized and their performance was tested successfully allowing moving to the first plasma operation phase. After a few attempts, plasma breakdown was achieved confirming that all systems were properly running and synchronized. Due to several micro air leaks on fiber optic feedthroughs and issues with the design of the in-vessel stabilizing plates, plasma current ramp-up could not be achieved in a first step. Once these issues have been fixed, confined plasmas could be obtained. Diverted plasmas were then achieved and the plasma current was increased up to 800 kA for more than 10 s. Up to 2.5 MW of additional power was eventually successfully coupled to the plasma. [ABSTRACT FROM AUTHOR]

The article demonstrates the first full-field imaging system using quantum illumination by an enhanced detection protocol. It mentions that the quantum illumination protocol differs from usual quantum schemes in that the advantage is maintained even in the presence of noise and loss. the importance of the suppression of background light and noise for quantum imaging.

The WEST platform consists in a major upgrade of Tore Supra towards a steady-state tungsten (W) diverted tokamak. In support of this, significant developments are performed on the measurement systems (diagnostics); the control, data access and communication (CODAC); the plasma control system (PCS), the monitoring and protection of the first wall and modelling to prepare the restart of the plasma. Thanks to collaboration agreements already in force, most of the developments and some hardware procurements are performed with the help of several international partners. This paper discusses the present status of developments regarding the measurements and control for the WEST project. In particular, the integration of about 50 diagnostics in ports is completed, and their in-vessel and ex-vessel installation is underway. The refurbishment of the CODAC network architecture has been completed. The development of the new acquisition units based on PXI and of the Plasma Control System (PCS) is ongoing and some units are already available. In parallel, to prepare the plasma restart, the development of plasma magnetic and kinetic controllers has been performed on simplified plant and actuator models and plasma models. [ABSTRACT FROM AUTHOR]

Abstarct: The operation of present day tokamak and future machine like ITER is more and more demanding in terms of plasma control both for increasing plasma performance, stability and ensuring machine protection. Additionally saving experimental time by validating the pre-programmed plasma scenario through a simulator is also of major importance. These issues highlight the necessity to build new tools such as a generic multipurpose plasma discharge flight simulator. Such a project has been recently started at CEA and is based on the integrated tokamak modeling task force formalism and simulation platform. The paper reports on the present status of the project, reviewing in particular the needs for new tool development, the architecture of the generic multipurpose tokamak plasma discharge flight simulator, with the different software/hardware interfaces. A first test case of this tool in the “full simulation” modes and using the European simulation platform is discussed. [Copyright &y& Elsevier]

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10−7). We identified a subgroup of patients presenting at diagnosis with both low β2-microglobulin <4 mg/l and high hemoglobin (Hb) 10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high β2-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.Leukemia (2007) 21, 2020–2024; doi:10.1038/sj.leu.2404832; published online 12 July 2007 [ABSTRACT FROM AUTHOR]

This report describes the long-term outcome of a cohort of 127 de novo multiple myeloma patients treated with at least one course of high-dose therapy (HDT) in a single institution between June 1985 and December 1995, for whom the minimum follow-up duration for survivors is 6 years. The 12-year overall survival (OS) and event-free survival (EFS) rates are 24.9% and 3.1%, respectively, and the median survival and EFS are 49 and 17 months, respectively. Only four patients are alive and disease-free 79, 90, 132 and 153 after the first HDT, respectively. Three of them received a subsequent allogeneic bone marrow transplantation. Three factors significantly influence OS in this series: B2M at diagnosis, age, and the completion of a second HDT. The 10-year survival is 18.9% for the group of patients with B2M level >3 mg/l at diagnosis as compared with 41% for patients with B2M ≤ 3, with a median survival of 31 months vs 73 (P = 0.01). The 10-year survival is 23.4% for the group of patients aged >55 years as compared with 36.5% for patients aged < 55 years, with a median survival of 34.5 months vs 70.5 (P = 0.04). The 10-year survival is 20.4% for the group of patients who did not receive a second HDT as compared with 35.2% for patients who completed a second HDT, with a median survival of 29 months vs 70 (P = 0.02). In this study we show that some patients treated with HDT experience durable remission and prolonged survival. This survival is significantly influenced by age (≤ 55 years), B2M at diagnosis (43 mg/l) and by the completion of two cycles of HDT. [ABSTRACT FROM AUTHOR]

FasL and TRAIL are apoptotic ligands of the TNF-like cytokines family, acting via activation of the transmembrane death domain containing receptors Fas for FasL, and DR4 or DR5 for TRAIL. A glycosylphosphatidylinositol-linked TRAIL receptor called DcR1 behaves as a decoy receptor inhibiting TRAIL-mediated cell death in several cellular systems. We engineered and stably expressed a chimeric GPI-linked Fas receptor (Fas-GPI) in T-lymphocyte cell lines constitutively expressing functional transmembrane Fas. Surprisingly, despite lacking the death domain region of functional Fas, Fas-GPI was able to significantly increase Fas-mediated cell death triggered by membrane bound or soluble FasL, whereas engagement of Fas-GPI alone did not trigger apoptosis. This potentiating effect, but not transmembrane Fas activation, was selectively inhibited by protein kinase C activation with phorbol esters, demonstrating that Fas-GPI activated a specific synergistic signal transduction pathway. Fas-GPI and transmembrane Fas were localized in distinct membrane compartments, since Fas-GPI, but not transmembrane Fas, was found in the glycolipid-rich membrane microdomains. These results suggest that apoptosis induced by members of this ligand/receptors family may be differentially modulated through other and parallel signalling pathways. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the therapeutic attributes and pathological conditions of the insulin-like growth factor-1 (IGF-1) receptor as an inhibitor of tumor cells growth and apoptosis in patients with multiple myeloma.

A letter to the editor is presented in response to the article "Stem cell collection in patients with de novo multiple myeloma treated with the combination of bortezomib and dexamethasone before autologous stem cell transplantation according to IFM 2005–01 trial," in April 29, 2010 issue.

• Remote experiment with WEST in Cadarache from Japan was successfully performed. • Pulse edit, discussion, monitoring and intershot analyses were feasible from remote. • Analyses of ITER by distributed computing resource with replicated data is proposed. Remote experiment with WEST tokamak in CEA Cadarache from ITER Remote Experimentation Centre (REC) in Rokkasho had been successfully carried out under the agreement between the Government of Japan and the European Atomic Energy Community for the joint implementation of the Broader Approach (BA) activities in the field of fusion energy research. The WEST and the REC sites were connected with the international broadband network for science and education of SINET, GÉANT and RENATER. Due to a long distance over 10,000 km of two sites, the latency was about 200 ms (round trip time) in total via the direct line between EU and Japan of SINET5. Based on the communication between local and remote participants, plasma discharges were successfully executed repeatedly according to the pulse schedule produced by remote Session Leader after the approval by Engineer in Charge on WEST site. Intershot analyses were successfully executed during the pulse interval on an analysis server prepared in Partners network in the WEST for external collaborator. Full function required for the remote experiments were successfully demonstrated in the large size tokamak facility, WEST. For remote participation of ITER, however, it is expected that the amount of experimental data and the number of remote participations will become very large. Distributed database system based on data replication using high-speed data transferring method and distributed computing resources in local and remote sites are proposed as a possible solution in ITER. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) is a new treatment option in patients with systemic AL amyloidosis (AL). The purpose of this review is to summarize the clinical experience of ASCT for AL, and to discuss the feasibility and the future developments of this new approach. [ABSTRACT FROM AUTHOR]

The article reports that directional cell motility relies on the ability of single cells to establish a front-rear polarity and can occur in the absence of external cues. Topics discussed include establishment of a one-dimensional microfabricated migration assay, generic stick-slip behavior initiated by contractility-dependent stochastic detachment of adhesive contacts at one side of the cell and the adhesion-dependent initiation of migration.

• Heat transfer coefficients were identify using experimental data • Radiative effects have been included and analyzed in the identification methodology • Thermocouple position and initial temperature impact the coefficient values This paper is devoted to the identification of the heat transfer coefficient between a high temperature glass and a cast iron punch taking radiative effect into account. A 1D numerical thermal model taking the radiative effects into account has been developed to simulate the contact between a punch and a glass cylinder. It was coupled with an inverse identification methodology to determine the heat transfer coefficient using experimental data carried out in the LAMIH. First, the sensitivity of the identification of the heat transfer coefficient with respect to different parameters (initial glass temperature, thermocouple position, radiation) will be introduced. A second part will show the identification of heat transfer coefficient using experimental data taking into account radiative effects. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing a prospective phase II trial of Rituximab infusions in patients with multiple myeloma expressing CD20.

Examines the effectiveness of clarithromycin in advanced multiple myeloma. Effectiveness of conventional chemotherapy followed by stem cell transplantation in the treatment of multiple myeloma; Patients information treated to examine the effectiveness of clarithromycin.

Abstract: Degradation of the electrochemical performance of LiFePO4 upon air exposure, assigned to a corrosion-type aging mechanism, implies the incorporation of hydroxyl groups and the formation of an amorphous tavorite-like phase at the surface. Using a carbon coating provides an efficient protection from this detrimental process but also modifies the surface in contact with the electrolyte. The formation and evolution of electrode/electrolyte interphases forming on both air-aged and carbon coated LiFePO4 are discussed based on combined quantitative 7Li, 19F MAS NMR, EIS and EELS measurements. Concerning the air-aged LiFePO4, the electrode/electrolyte interactions are dominated by the dissolution of the active material and an exacerbated reaction of incorporated hydroxyl groups with the electrolyte salt, resulting in a LiF rich interphase. This dissolution of the outer part of active material particles is accompanied by the departure of the previously formed interphase and a new interphase is then formed on a newly exposed surface. The resistive LiF rich interphase passivates the active material particles during cycling, forming a resistive film, hindering both Li ion transfer and material corrosion. Cellulose acetate based carbon coating prevents air-aging but yields to an accumulation of organic lithiated species, allowing Li transfer and maintaining good electrochemical performance. [Copyright &y& Elsevier]

To determine whether isotype matched immunoglobulin (Ig; Ig'κ/Ig'λ) ratios had prognostic significance in patients with intact Ig multiple myeloma (MM). Novel immunoassays measuring serum concentrations of the Ig heavy chain/light chain (HLC) subsets IgGκ, IgGλ, IgAκ and IgAλ were compared with monoclonal protein ('M-spike') quantification by serum protein electrophoresis, β(2)-microglobulin (β(2)-M), albumin, serum free light chain (FLC) and cytogenetic markers in relation to outcome in 339 MM patients. Abnormal IgGκ/IgGλ and IgAκ/IgAλ ratios present in the respective tumor isotypes at clinical presentation were predictive of shorter progression-free survival (PFS) (hazard ratio (HR) 1.9; P=0.0002), predominantly due to the suppression of the uninvolved (polyclonal) Ig of the same isotype as the tumor (HR 1.8; P=0.002). No significant associations were observed between PFS and M-spike concentrations, suppression of non-tumor Igs of different isotypes or FLC κ/λ ratios. β(2)-M and HLC ratios were independently prognostic (P=0.045 and P=0.001). A staging system using β(2)-M and extreme HLC ratios (<0.01 or >200) had greater prognostic value than the widely used ISS staging system (HR 1.7; P=0.00002 vs HR 1.3; P=0.017). These results suggest that HLC ratios may have a role in clinical management of MM. [ABSTRACT FROM AUTHOR]

Presents a longitudinal study on epidemiology of bacterial, fungal and viral infections in adult recipients of bone marrow transplants. Uses of bone marrow transplantation; Patients and methods; Results of the study; Discussion.

In order to determine the clinical impact of CD34+ cell selected autologous transplantation in multiple myeloma (MM), we have performed a retrospective case-controlled analysis comparing 21 MM patients receiving high-dose melphalan and autologous transplantation with CD34+ peripheral blood stem cells (PBSC) as front-line therapy to 21 control patients receiving unselected products. Case matching was performed using the following criteria: age and beta2-microglobulin at diagnosis and disease status at the time of transplantation. Both cohorts were homogeneous in term of induction treatment and conditioning regimen. Patients were collected for CD34+ selection after priming with G-CSF alone. Significantly fewer CD34+ cells/kg were infused to patients in the selected group as compared to patients in the control group: 2.2 (range 0.5-14.3) vs 9.4 (range 1.1-15) (P < 0.001). The median time to neutrophil recovery > or =0.05 x 10(9)/l was 10 days for the CD34+ group and 9.5 days for the control group (P = 0.357). The median time to platelet recovery > or = 20 x 10(9)/l was 9 days for the CD34+ group and 4.5 days for the control group (P = 0.005). Response rates were comparable in both groups (85.7% in the CD34+ group vs 90.4% in the control group). At 3 years, event-free survival (32% in the CD34+ group vs 39% in the control group) and overall survival (85% in the CD34+ group vs 79% in the control group) were not significantly different. Finally, use of unselected products dramatically reduced the cost of the transplantation procedure. This study shows that CD34+ cell selected autologous transplantation is more expensive than transplantation with unselected products and does not improve the clinical outcome of patients with MM. [ABSTRACT FROM AUTHOR]

As currently delineated, Hygrophorus sect. Olivaceoumbrini is a polyphyletic assembly within subg. Colorati, encompassing glutinous and pigmented taxa. According to available literature, between a dozen and twenty species may belong in the section, mostly represented in continental and boreal forests of Europe and North America. However, the limited phylogenetic and biogeographic coverage of the genus does not presently allow for a reliable assessment of its taxonomic boundaries, nor does it provide a complete picture of species diversity within sect. Olivaceoumbrini. In an ongoing effort to confer an evolutionary backbone to Hygrophorus systematics, we assembled and analysed a dataset comprising 268 intercontinental sequences, including holotypes of 7 taxa previously not positioned phylogenetically, and enriched with collections from largely unexplored Mediterranean and Anatolian ecosystems. Overall, 30 clades are identified within 5 distinct lineages, including 11 species putatively new to science. Seven of these are formally described here as H. agathosmoides, H. albofloccosus, H. canadensis, H. limosus, H. marcocontui, H. pinophilus and H. pustulatoides spp. nov. This enriched coverage of section Olivaceoumbrini s.lat. calls for a re-evaluation of its natural boundaries into a core monophyletic clade, including H. olivaceoalbus and five closely related lookalikes, as well as the assignment of the section rank to the four remaining lineages: sect. Fuscocinerei sect. nov., sect. Limacini sect. nov., sect. Nudolidi sect. nov. and sect. Tephroleuci, respectively. We also stabilize the usage of six historical names, H. glutinifer, H. hyacinthinus, H. mesotephrus, H. olivaceoalbus, H. pustulatus and H. tephroleucus, through designation of two neotypes, three lectotypes and four epitypes. [ABSTRACT FROM AUTHOR]

The experimental flow stress curves of structural steels obtained from axisymmetric compression tests conducted under hot-working conditions very often include the frictional effects present at the tool/specimen interface. Such effects have a significant influence on the flow stress and therefore, should be corrected prior to any quantitative analysis aimed at determining the constitutive description of these materials. Commonly, such a correction is carried out by assuming a constant friction coefficient (μ) or friction factor (m) independent of deformation conditions, which is an unrealistic approach. The present investigation analyzes experimentally the frictional effects that occur when steel is deformed under axisymmetric compression conditions in the temperature range of 850 to 1200 °C at a strain rate of 0.1 s−1 and applied effective strains of 1, employing cylindrical samples with an initial diameter to initial height ratio (d0/h0) in the range of 0.5 to 2. Finite element modeling (FEM), as well as element-free Galerkin modeling (EFGM), have been employed for the analysis and prediction of the von Mises stress distribution, barreling and amount of metal folding undergone by the compression specimens. It has been shown that the increase in flow stress due to frictional effects can be corrected on the basis of either μ or m, by assuming that these parameters vary in the course of plastic deformation and are strongly dependent on deformation temperature. A novel procedure for the systematic correction of the flow stress curves, taking into consideration the changes in friction conditions during plastic deformation, has been proposed. [ABSTRACT FROM AUTHOR]

The WEST project has consisted in modifying the Tore Supra tokamak magnetic configuration to achieve X-point by adding divertor coils in the vacuum vessel and to test ITER-like plasma facing components. Major changes and significant developments have been performed on the measurement systems (diagnostics); the control, data access and communication; the plasma control system, and the actuators. To keep track of the software developments and step by step upgrade performed on any subsystem of the tokamak, a software quality management procedure has been implemented. This procedure consists also of a validation workflow ensuring that only validated version of the software are used during a plasma discharge. Such procedure is successfully used since 2 years. [ABSTRACT FROM AUTHOR]

The new WEST configuration of Tore Supra facility leads to control challenges and the need to handle events of a modern diverted and metallic machine (vertical stabilization, impurity control, ...). To address them, a new Plasma Control System (PCS) has been built based on the ASDEX upgrade (AUG) real-time framework called DCS (Discharge Control System). This contribution summarizes the work done during the 5 years of the project from the definition of the PCS concepts to its operation during the WEST campaigns. The integration into the Tore Supra control infrastructure is detailed as well as the different real-time control processes. The efficiency and the versatility of the PCS are illustrated by several examples of plasma operation. [ABSTRACT FROM AUTHOR]

The present paper deals with the surface heat flux estimation with thermocouples (TC) and fiber Bragg grating (FBG) embedded in the plasma facing components (PFC) of the WEST tokamak. A 2D heat transfer model combined with the conjugate gradient method and the adjoint state is used to estimate the plasma heat flux deposited on the PFC. The plasma heat flux is characterized by the time evolution of its amplitude and spatial shape on the target (heat flux decay length λ q t , power spreading in the private flux region S t and the strike point location x 0). As a first step, five ohmic pulses have been investigated with different magnetic configuration and divertor X-point height varying from 44 to 68 mm from the surface. Despite an outboard shift, the relative displacements of the outer strike point as well as the heat flux decay length derived from the TC/FBG systems are consistent with the magnetic equilibrium reconstruction. [ABSTRACT FROM AUTHOR]

Highlights • Ten channels with common retroreflectors and windows were repositioned in the WEST tokamak environment for a 0.1 normalized radius resolution. • Inner vessel mirrors close to the divertor allow the X point and edge plasma diagnose. • Digital electronics replaces the initial data processing electronics. • Data were routinely and trouble free produced for real time control at 1 ms sampling time and post pulse analysis with mixed 1 MHz and 1 ms sampling time during the 2 year first WEST plasma campaign. Abstract In the frame of the WEST tokamak upgrade project, the Tore Supra combined interferometer-polarimeter diagnostic has been modified to fit the geometry and constraints induced by the implementation of divertor coils in the vacuum vessel. For a good spatial resolution of the plasma, as the vertical ports are now partially obstructed, 8 infrared beams go through a common horizontal port and are retro-reflected on an inner panel and 2 vertical port retro-reflected channels, with specific vacuum mirrors close to the divertor, could be implemented to diagnose the edge plasma. The electronics and the data acquisition have also been renewed to improve the reliability and precision of the measurements. Novel digital electronics with embedded interferometric and polarimetric algorithms produce 1 ms data outputs for real time control. The diagnostic has routinely been operated during the first WEST campaigns. In this article, we detail the new arrangement and discuss the first results with plasma. [ABSTRACT FROM AUTHOR]

In this paper, we investigate dilepton production in heavy‐ion collisions from sNN=8 to 200 GeV with a focus on the competition between the thermal quark‐gluon plasma (QGP) radiation and the semi‐leptonic decays from correlated D‐meson pairs. As a "tool," we employ the parton–hadron string dynamics (PHSD) transport approach incorporating a fully microscopic treatment of the charm dynamics and their semi‐leptonic decays. We find that the dileptons from correlated D‐meson decays dominate the "thermal" radiation from the QGP in central Pb + Pb collisions at the intermediate masses (1.2 GeV < M < 3 GeV) for sNN>40GeV, while for sNN=5−20GeV, the contribution from D,D‾ decays to the intermediate mass dilepton spectra is subleading such that one should observe a rather clear signal from the QGP radiation, which is dominated by the annihilation channel qq‾→γ*. [ABSTRACT FROM AUTHOR]

Abstract The WEST (Tungsten Environment for Steady State Tokamak) platform aims at testing ITER like divertor targets in an integrated tokamak environment, to minimize risks for procurement and operation. After 4 years of construction, WEST is now operational, with the first plasma breakdown achieved in December 2016. To operate long plasma discharge in WEST, infrared thermography is a key device, which enables a safe operation by means of a real time surface temperature monitoring, while providing essential data for various physics studies. For WEST, the IR thermography system has been deeply renewed, to match with the new tokamak configuration, and to fulfil the new measurement requirements. It consists of a set of 5 different diagnostics: 1) 7 endoscopes located in upper ports viewing the whole lower divertor and the 5 heating devices 2) a tangential endoscope located in a median port, providing a wide angle view of the vacuum vessel, and in particular of the upper divertor and first wall protections 3) a submillimetre resolution view on the divertor strike points from an upper port endoscope 4) 2 additional views of the divertor and of the heating devices. The paper describes the new IR diagnostics configuration (spatial covering, IR cameras, optics, data processing hardware and software), the main design options, manufacturing and installation issues, and some measurement performances. [ABSTRACT FROM AUTHOR]

New fueling systems have been designed for WEST, a full tungsten wall tokamak with divertor configuration. They consist of standard gas injection, supersonic molecular beam injection and pellets injection systems, each being able to fuel continuously the plasma discharge up to a duration of 1000s. A massive gas injection system is also implemented to mitigate the impact of disruptions and runaway electrons. The standard gas system consists of 4 independent lines allowing the injection of up to 4 different gas species during a plasma discharge through 11 injections areas, 4 of them being located in the divertors and in the private flux region. The pellet injection system is able to inject up to 10 pellets per second through 4 tracks: one on the low field side, and the other 3 on the high field side. The supersonic molecular beam injection system consists of 3 injectors located close to the midplane, two on the high field side and one on the low field side. On trigger, the massive gas injection system can deliver in a single puff up 800 Pa.m3 of noble gas in order to stop the plasma discharge. All the fueling systems have been characterized and can be used routinely on plasma. [ABSTRACT FROM AUTHOR]

In December 2016, the experimental Tokamak WEST (W -for Tungsten- Environment in Steady state Tokamak) has produced its first plasma using its new Plasma Control System (PCS) based on the AUG RT framework DCS (Discharge Control System) and adapted to the specific needs of WEST. Now, WEST project’s development phase ends and a first operational version is routinely used for experimental purpose. [ABSTRACT FROM AUTHOR]

Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed. In this review, a panel of expert European hematologists updates the recommendations on the diagnosis and management of patients with solitary plasmacytoma. [ABSTRACT FROM AUTHOR]

Control of a Tokamak requires operating many sophisticated control loops in a dynamic sequence of activities. To take appropriate actions in case technical or physics conditions occur unexpectedly, the continuous control must be backed up by Exception Handling (EH) logic. To mature the Conceptual Design of the ITER Plasma Control System (PCS) with such logic for the Preliminary Design, we studied, in a formal process, how the plasma will be controlled during the 1 st plasma and early operation phases of ITER and analysed the required control and EH functions and dependencies: Three classes of Exception Handling were identified which cover all use cases: modification of the control behaviour of a single control function, modification of the control structure of connected controllers, and change of the control goal which modifies the overall control system. The three classes form a EH hierarchy from low to high impact responses that can be implemented as local EH in the Pulse Continuous Control layer and as central EH in the Pulse Supervision layer of the PCS. [ABSTRACT FROM AUTHOR]

Elaphomyces ('deer truffles') is one of the most important ectomycorrhizal fungal genera in temperate and subarctic forest ecosystems, but also one of the least documented in public databases. The current systematics are mainly based on macromorphology, and is not significantly different from that proposed by Vittadini (1831). Within the 49 species recognised worldwide, 23 were originally described from Europe and 17 of these were described before the 20th century. Moreover, very recent phylogenetic treatments of the genus are mainly based on a few extra-European species and most common European species are still poorly documented. Based on an extensive taxonomic sampling mainly made in the biogeographically rich Cantabrian area (Spain), complemented with collections from France, Greece, Italy, Norway, Portugal and Sweden, all currently recognized species in Europe have been sequenced at the ITS and 28S of the rDNA. Combined phylogenetic analyses yielded molecular support to sections Elaphomyces and Ceratogaster (here emended), while a third, basal lineage encompasses the sections Malacodermei and Ascoscleroderma as well as the tropical genus Pseudotulostoma. Species limits are discussed and some taxa formerly proposed as genuine species based on morphology and biogeography are re-evaluated as varieties or forms. Spore size and ornamentation, features of the peridial surface, structure of the peridium, and the presence of mycelium patches attached to the peridial surface emerge as the most significant systematic characters. Four new species: E. barrioi, E. quercicola, E. roseolus and E. violaceoniger, one new variety: E. papillatus var. sulphureopallidus, and two new forms: E. granulatus forma pallidosporus and E. anthracinus forma talosporus are introduced, as well as four new combinations in the genus: E. muricatus var. reticulatus, E. muricatus var. variegatus, E. papillatus var. striatosporus and E. morettii var. cantabricus. Lectotypes and epitypes are designated for most recognised species. For systematic purposes, new infrageneric taxa are introduced: E. sect. Ascoscleroderma stat. nov., E. subsect. Sclerodermei stat. nov., E. subsect. Maculati subsect. nov., E. subsect. Muricati subsect. nov., and E. subsect. Papillati subsect. nov. Lastly, E. laevigatus, E. sapidus, E. sulphureopallidus and E. trappei are excluded from the genus and referred to Rhizopogon roseolus, Astraeus sapidus comb. nov., Astraeus hygrometricus and Terfezia trappei comb. nov. (syn.: Terfezia cistophila), respectively. [ABSTRACT FROM AUTHOR]

Infrageneric relations of the genetically diverse milkcap genus Lactifluus (Russulales, Basidiomycota) are poorly known. Currently used classification systems still largely reflect the traditional, mainly morphological, characters used for infrageneric delimitations of milkcaps. Increased sampling, combined with small-scale molecular studies, show that this genus is underexplored and in need of revision. For this study, we assembled an extensive dataset of the genus Lactifluus, comprising 80 % of all known species and 30 % of the type collections. To unravel the infrageneric relationships within this genus, we combined a multi-gene molecular phylogeny, based on nuclear ITS, LSU, RPB2 and RPB1, with a morphological study, focussing on five important characteristics (fruit body type, presence of a secondary velum, colour reaction of the latex/context, pileipellis type and presence of true cystidia). Lactifluus comprises four supported subgenera, each containing several supported clades. With extensive sampling, ten new clades and at least 17 new species were discovered, which highlight the high diversity in this genus. The traditional infrageneric classification is only partly maintained and nomenclatural changes are proposed. Our morphological study shows that the five featured characteristics are important at different evolutionary levels, but further characteristics need to be studied to find morphological support for each clade. This study paves the way for a more detailed investigation of biogeographical history and character evolution within Lactifluus. [ABSTRACT FROM AUTHOR]

Design of the ITER plasma control system is proceeding towards its next – preliminary design – stage. During the conceptual design in 2013 an overall assessment of high-level control tasks and their relationships has been conducted. The goal of the preliminary design is to show, that a reasonable implementation of the proposed concepts exists which fulfills the high-level requirements and is suitable for realistic use cases. This verification is conducted with focus on the concrete use cases of early operation and first plasma, since these phases are mandatory for ITER startup. In particular, detailed control requirements and functions for commissioning and first plasma operation including breakdown, burn-through and ramp-up in L-mode, as well as for planned or exceptional shutdown are identified. Control functions related to those operational phases and the underlying control system architecture are modeled. The goal is to check whether the flexibility of the conceptual architectural approach is adequate also in consideration of the more elaborate definitions for control functions and their interactions. In addition, architecture shall already be prepared for extension to H-mode operation and burn-control, even if the related control functions are only roughly defined at the moment. As a consequence, the architectural design is amended where necessary and converted into base components and infrastructure services allowing to deploy control and exception handling algorithms for the concrete first-plasma operation. [ABSTRACT FROM AUTHOR]

Background: Therapeutic advancements following the introduction of autologous stem cell transplantation and 'novel' agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians. Design: A Panel of International Myeloma Working Group members reviewed the most relevant data published in the literature as full papers, or presented at meetings of the American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, or International Myeloma Workshops, up to June 2016. Here, we present the recommendations of the Panel, based on this literature review. Results: Overall, the risk of SPMs in MM is low, multifactorial, and partially related to the length of patients' survival and MM intrinsic susceptibility. Studies suggest a significantly increased incidence of SPMs when lenalidomide is administered either following, or concurrently with, oral melphalan. Increased SPM incidence has also been reported with lenalidomide maintenance following high-dose melphalan, albeit to a lesser degree. In both cases, the risk of death from MM was significantly higher than the risk of death from SPMs, with lenalidomide possibly providing a survival benefit. No increase in SPM incidence was reported with lenalidomide plus dexamethasone (without melphalan), or with bortezomib plus oral melphalan, dexamethasone, or thalidomide. Conclusion: In general, the risk of SPMs should not alter the current therapeutic decision-making process in MM. However, regimens such as lenalidomide plus dexamethasone should be preferred to prolonged exposure to lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the patient in the context of benefits and risks of different treatment options. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous (s.c.) administration of bortezomib is the most widely used route of administration for the treatment of patients with multiple myeloma. No study has as yet prospectively evaluated home versus hospital administration of s.c. bortezomib with respect to patient preference and cost. Patients and methods: In this prospective trial, myeloma patients received the first administration of s.c. bortezomib of each cycle in the outpatient unit of the Department of Hematology. When possible, all subsequent doses of bortezomib within each cycle were provided at home. A cost analysis was carried out to compare the average cost of an injection of bortezomib in the outpatient unit and at home. In order to compare hospital and home administration of bortezomib for preference and satisfaction, patients had to complete 2 simple questionnaires analyzing 16 criteria, such as quality of life, well-being, social life, satisfaction, safety, quality of care, the reduction in personal transportation time, and personal anxiety. Each item was analyzed using a Likert scale. Results: Fifty patients were studied. Overall, a total of 1043 s.c. injections of bortezomib were carried out, 655 (62.8%) at home, and 388 (35.2%) in the outpatient unit. The cost analysis showed that the total cost of one s.c. injection of bortezomib in the outpatient unit was ∊1510.09 versus ∊1224.57 for the home administration, which represents a reduction of ∊285.52, i.e. 20% of the cost of the hospital administration. The evaluation of patient preference and satisfaction showed that home administration improved the quality of life in 84% of the patients, increased well-being in 78%, and improved the activities of daily living in 72% of the cases. Overall, 98% of the patients noted their preference for home administration over the hospital administration of bortezomib. Conclusion: Home administration of s.c. bortezomib is cost-effective and is preferred by myeloma patients compared with hospital administration. [ABSTRACT FROM AUTHOR]

The configuration of the Tore Supra WEST project leads to control challenges and event handling close to those of ITER from a plasma scenario point of view (X-point configuration, H mode, long duration pulse) and from a machine protection point of view (metallic environment). Based on previous conceptual studies and to meet the WEST requirements, a sub-project will implement a new plasma control system (PCS) and a new pulse schedule editor (PSE). The main idea is to use a segment approach to describe the pulse scheduling with a full integration of event handling both on the PCS and on the PSE. After detailed specification work, it has been shown that the real-time framework called DCS (Discharge Control System) which is currently used on ASDEX upgrade fulfills the requirements and could be integrated into the WEST global control infrastructure. For the PSE, the Xedit tool, developed for the future W7X facility, has been chosen. This contribution will begin by a short explanation of the concepts proposed for the control of the plasma and the handling of events during the plasma discharge. Then it will focus on the new centralized architecture of the new Tore Supra PCS and an operating principle example showing the efficiency of the approach to handle normal and off-normal events. This later point will illustrate the required modifications of DCS and Xedit to fit with the Tore Supra Control infrastructure. [ABSTRACT FROM AUTHOR]

Background Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation ( HSCT). Chemotherapy leads to several side effects, with gastrointestinal ( GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome. Aim To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy. Methods We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics. Results We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes ( P = 0.0002) and Actinobacteria ( P = 0.002) and significant increases in abundances of Proteobacteria ( P = 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism ( P = 0.0001), energy metabolism ( P = 0.001), metabolism of cofactors and vitamins ( P = 0.006), and increased capacity for glycan metabolism ( P = 0.0002), signal transduction ( P = 0.0002) and xenobiotics biodegradation ( P = 0.002). Conclusions Our study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy-induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome-targeted interventions in cancer patients. [ABSTRACT FROM AUTHOR]

A poorly understood feature of the tauopathies is their very different clinical presentations. The frontotemporal lobar degeneration (FTLD) spectrum is dominated by motor and emotional/psychiatric abnormalities, whereas cognitive and memory deficits are prominent in the early stages of Alzheimer's disease (AD). We report two novel mouse models overexpressing different human tau protein constructs. One is a full-length tau carrying a double mutation [P301S/G335D; line 66 (L66)] and the second is a truncated 3-repeat tau fragment which constitutes the bulk of the PHF core in AD corresponding to residues 296-390 fused with a signal sequence targeting it to the endoplasmic reticulum membrane (line 1; L1). L66 has abundant tau pathology widely distributed throughout the brain, with particularly high counts of affected neurons in hippocampus and entorhinal cortex. The pathology is neuroanatomically static and declines with age. Behaviourally, the model is devoid of a higher cognitive phenotype but presents with sensorimotor impairments and motor learning phenotypes. L1 displays a much weaker histopathological phenotype, but shows evidence of neuroanatomical spread and amplification with age that resembles the Braak staging of AD. Behaviourally, the model has minimal motor deficits but shows severe cognitive impairments affecting particularly the rodent equivalent of episodic memory which progresses with advancing age. In both models, tau aggregation can be dissociated from abnormal phosphorylation. The two models make possible the demonstration of two distinct but nevertheless convergent pathways of tau molecular pathogenesis. L1 appears to be useful for modelling the cognitive impairment of AD, whereas L66 appears to be more useful for modelling the motor features of the FTLD spectrum. Differences in clinical presentation of AD-like and FTLD syndromes are therefore likely to be inherent to the respective underlying tauopathy, and are not dependent on presence or absence of concomitant APP pathology. [ABSTRACT FROM AUTHOR]

Background: Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous diseases with dismal outcome when treated with chemotherapy alone. Because allogeneic stem-cell transplantation (allo-SCT) can cure relapse/refractory patients, we hypothesized that upfront allo-SCT may provide a better outcome. Therefore, all patients that presented with advanced PTCL in our institution at diagnosis were scheduled to undergo upfront allo-SCT after induction chemotherapy. Patients and methods: The aim of the present work was to assess the feasibility and toxicity of upfront allo-SCT. From 2004 to 2012, 49 newly diagnosed PTCL patients were scheduled to receive upfront allo-SCT. A human leukocyte antigen-matched donor was found for 42 patients: related to the patient in 15 cases, unrelated in 20 cases, and suitable cord blood units were used in 7 cases. Results: After induction chemotherapy, 17 patients reached complete remission and 29 (60%) proceeded to upfront allo-SCT. For all patients, the 1 and 2-year overall survival (OS) rates were 59% [95% confidence interval (CI) 47–75] and 55% (95% CI 43–71), respectively. The most frequent reason we did not proceed to allo-SCT was disease progression or insufficient response after induction. For transplanted patients, the 1- and 2-year OS were 76% (95% CI 62–93) and 72.5% (95% CI 58–91), respectively. Toxicity-related mortality (TRM) 1 year after allo-SCT was only 8.2% (95% CI 0–18.5). The 2-year progression-free survival (PFS) rate of patients who did not proceed to allo-SCT (n = 20) was below 30%. The disease status at the time of transplantation was a strong predictive marker for both PFS and OS in transplant patients. Conclusions: Upfront allo-SCT in PTCLs is feasible with low TRM, and it provides long-term disease control. However, one-third of patients remain chemo-refractory and, thus, new therapeutic approaches are warranted. The role of upfront allo-SCT compared with other therapeutic approaches in PTCLs requires investigation in randomized studies. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen-G (HLA-G) has well-recognized immunosuppressive properties modulating the activity of many immune system cells, and polymorphisms observed at the HLA-G 5′ upstream regulatory region (5′URR) may influence gene transcriptional regulation. In this study, we characterized the sequence variation and haplotype structure of the HLA-G 5′URR in worldwide populations to investigate the evolutionary history of the HLA-G promoter and shed some light into the mechanisms that may underlie HLA-G expression control. A 1.4-kb region, encompassing the known HLA-G regulatory elements, was sequenced in three African populations from Senegal, Benin and Congo, and data were combined with those available in the literature, resulting in a total of 1411 individuals from 21 worldwide populations. High levels of nucleotide and haplotype diversities, excess of intermediate-frequency variants and reduced population differentiation were observed at this locus when compared with the background genomic variation. These features support a strong molecular signature of balancing selection at HLA-G 5′URR, probably as a result of the competing needs to maintain both a maternal-fetal immune tolerance and an efficient host immune response to invading pathogens during human evolution. An extended analysis of a 300-kb region surrounding HLA-G revealed that this region is not involved in a hitchhiking effect and may be the direct target of selection. [ABSTRACT FROM AUTHOR]

With advent of several treatment options in multiple myeloma (MM), a selection of effective regimen has become an important issue. Use of gene expression profile (GEP) is considered an important tool in predicting outcome; however, it is unclear whether such genomic analysis alone can adequately predict therapeutic response. We evaluated the ability of GEP to predict complete response (CR) in MM. GEP from pretreatment MM cells from 136 uniformly treated MM patients with response data on an IFM, France led study were analyzed. To evaluate variability in predictive power due to microarray platform or treatment types, additional data sets from three different studies (n=511) were analyzed using same methods. We used several machine learning methods to derive a prediction model using training and test subsets of the original four data sets. Among all methods employed for GEP-based CR predictive capability, we got accuracy range of 56-78% in test data sets and no significant difference with regard to GEP platforms, treatment regimens or in newly diagnosed or relapsed patients. Importantly, permuted P-value showed no statistically significant CR predictive information in GEP data. This analysis suggests that GEP-based signature has limited power to predict CR in MM, highlighting the need to develop comprehensive predictive model using integrated genomics approach. [ABSTRACT FROM AUTHOR]

In this report, a panel of European myeloma experts discuss the role of pomalidomide in the treatment of relapsed and refractory multiple myeloma (RRMM). Based on the available evidence, the combination of pomalidomide and low-dose dexamethasone is a well-tolerated and effective treatment option for patients with RRMM who have exhausted treatment with lenalidomide and bortezomib. The optimal starting dose of pomalidomide is 4 mg given on days 1-21 of each 28-day cycle, whereas dexamethasone is administered at a dose of 40 mg weekly (reduced to 20 mg for patients aged >75 years). The treatment should continue until evidence of disease progression or unacceptable toxicity. Dose-modification schemes have been established for patients who develop neutropenia, thrombocytopaenia and other grade 3-4 adverse events during pomalidomide therapy. Guidance on the prevention and management of infections and venous thromboembolism is provided, based on the available clinical evidence and the experience of panel members. The use of pomalidomide in special populations, such as patients with advanced age, renal impairment or unfavourable cytogenetic features, is also discussed. [ABSTRACT FROM AUTHOR]