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BACKGROUND Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma. METHODS In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better). RESULTS Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2). CONCLUSIONS Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.). [ABSTRACT FROM AUTHOR]

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]

L'erreur de diagnostic est relativement fréquente en rhumatologie. La pensée médicale utilise différentes ressources, pendant l'interaction médecin–patient. Ses ressources cognitives ne sont pas forcément conscientes, et elles utilisent des voies neuronales tantôt rapides, de l'ordre du réflexe ; tantôt réflexives, lentes et coûteuses en énergie. En pratique clinique, le rhumatologue est soumis à une pression au cours de sa consultation, pour décider, alors qu'il dispose d'informations incomplètes. Il doit alors combiner réflexion et action en un temps contraint. Le raisonnement médical utilise alors des raccourcis de la pensée appelés heuristiques. Ce système cognitif rapide est le plus souvent pertinent, mais peu rigoureux et il peut dans certains cas aboutir à des erreurs. Elles sont alors liées à des dévoiements du raisonnement médical rationnels et constituent la contrepartie négative de ces heuristiques. Des cas cliniques ayant aboutis à une erreur de prise en charge ou de diagnostic ont été sélectionnés de manière hebdomadaire et analysés en groupe durant une période de 6 semaines. L'attention étant portée sur le raisonnement médical « technique » mais aussi sur les aspects émotionnels ayant pu contribuer à l'erreur. Les biais cognitifs peuvent affecter les différentes pratiques (libérale et/ou hospitalière). Plusieurs biais cognitifs ont pu être mis en évidence. Les biais les plus classiques, comme le biais d'ancrage, le biais de confirmation, sont liés à un trop fort attachement à un diagnostic particulier. À ce titre, le biais du scénario le plus rare est pour la première fois décrit. D'autres biais sont liés à la pathologie et à son mode de diagnostic. Les diagnostics d'élimination comme la fibromyalgie favorisent le biais de fermeture prématurée. Sur le plan individuel, les biais émotionnels sont favorisés, notamment en contexte d'incertitude. La pratique médicale en équipe n'est pas épargnée et est sujette à des biais propres, comme le biais de momentum, le biais de cadrage, et l'instinct de horde. Les biais cognitifs existent et sont inhérents à l'exercice médical. Leur reconnaissance constitue une démarche préliminaire mais indispensable, afin d'envisager des stratégies pour s'en prémunir. [ABSTRACT FROM AUTHOR]

Summary: Membrane trafficking is critical for cell compartmentation which allows the maintenance of specialised environments required for specific cellular activities. To achieve this goal, cells need to tightly regulate vesicle transport between donor and acceptor compartments. Several different protein families are involved: among them the SNAREs (65 genes) and the small GTPases Rabs (57 genes) show the highest number of isoforms and will be in the spotlight. We will focus on the roles of these proteins in the ER–Golgi–plasma membrane pathway to illustrate how Rabs and SNAREs are involved to achieve specific set of functions. Lay Description: Protein and lipid transport between the different compartments inside cells are critical for many physiological functions of organisms. To achieve this goal, cells have developed several vesicular transport systems between these compartments. Numerous different protein families are involved in these processes among which two protein families are the focus of the review in plant cells: the SNAREs and the small GTPases Rabs. These proteins are essentially controlling the different steps of the transport processes to warrant that proteins and lipids will reach the right compartments. The SNAREs are encoded by 65 genes meaning that plant cells synthesise 65 different SNARE proteins, and the small GTPases Rabs are encoded by 57 genes meaning that plant cells synthesise 57 different GTPases Rabs proteins. This high number of proteins illustrates the complexity of the vesicular transport systems existing between plant cell compartments. The review discusses the different roles of these proteins in these processes and particularly in the functioning of the secretory pathway which contributes to transport proteins and lipids to the cell surface. The review describes how the Rabs and SNAREs proteins are involved to achieve their respective set of functions in the different transport pathways of plant cells, and illustrates the tremendous complexity of these mechanisms. [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.

We study the effect of the chiral symmetry restoration (CSR) on heavy-ion collisions observables in the energy range s NN = 3 – 20 GeV within the Parton-Hadron-String Dynamics (PHSD) transport approach. The PHSD includes the deconfinement phase transition as well as essential aspects of CSR in the dense and hot hadronic medium, which are incorporated in the Schwinger mechanism for particle production. Our systematic studies show that chiral symmetry restoration plays a crucial role in the description of heavy-ion collisions at s NN = 3 – 20 GeV , realizing an increase of the hadronic particle production in the strangeness sector with respect to the non-strange one. Our results provide a microscopic explanation for the horn structure in the excitation function of the K + / π + ratio: the CSR in the hadronic phase produces the steep increase of this particle ratio up to s NN ≈ 7 GeV , while the drop at higher energies is associated to the appearance of a deconfined partonic medium. Furthermore, the appearance/disappearance of the horn structure is investigated as a function of the system size. We additionally present an analysis of strangeness production in the ( T , μ B ) -plane (as extracted from the PHSD for central Au+Au collisions) and discuss the perspectives to identify a possible critical point in the phase diagram. [ABSTRACT FROM AUTHOR]

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]

Background: Ixazomib is an oral proteasome inhibitor that is currently being studied for the treatment of multiple myeloma.Methods: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma to receive ixazomib plus lenalidomide-dexamethasone (ixazomib group) or placebo plus lenalidomide-dexamethasone (placebo group). The primary end point was progression-free survival.Results: Progression-free survival was significantly longer in the ixazomib group than in the placebo group at a median follow-up of 14.7 months (median progression-free survival, 20.6 months vs. 14.7 months; hazard ratio for disease progression or death in the ixazomib group, 0.74; P=0.01); a benefit with respect to progression-free survival was observed with the ixazomib regimen, as compared with the placebo regimen, in all prespecified patient subgroups, including in patients with high-risk cytogenetic abnormalities. The overall rates of response were 78% in the ixazomib group and 72% in the placebo group, and the corresponding rates of complete response plus very good partial response were 48% and 39%. The median time to response was 1.1 months in the ixazomib group and 1.9 months in the placebo group, and the corresponding median duration of response was 20.5 months and 15.0 months. At a median follow-up of approximately 23 months, the median overall survival has not been reached in either study group, and follow-up is ongoing. The rates of serious adverse events were similar in the two study groups (47% in the ixazomib group and 49% in the placebo group), as were the rates of death during the study period (4% and 6%, respectively); adverse events of at least grade 3 severity occurred in 74% and 69% of the patients, respectively. Thrombocytopenia of grade 3 and grade 4 severity occurred more frequently in the ixazomib group (12% and 7% of the patients, respectively) than in the placebo group (5% and 4% of the patients, respectively). Rash occurred more frequently in the ixazomib group than in the placebo group (36% vs. 23% of the patients), as did gastrointestinal adverse events, which were predominantly low grade. The incidence of peripheral neuropathy was 27% in the ixazomib group and 22% in the placebo group (grade 3 events occurred in 2% of the patients in each study group). Patient-reported quality of life was similar in the two study groups.Conclusions: The addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited. (Funded by Millennium Pharmaceuticals; TOURMALINE-MM1 ClinicalTrials.gov number, NCT01564537.). [ABSTRACT FROM AUTHOR]

The failure mechanism of silicon-based electrodes has been studied only in a half-cell configuration so far. Here, a combination of 7Li, 19F MAS NMR, XPS, TOF-SIMS, and STEM-EELS, provides an in-depth characterization of the solid electrolyte interphase (SEI) formation on the surface of silicon and its evolution upon aging and cycling with LiNi1/3Mn1/3Co1/3O2 as the positive electrode in a full Li-ion cell configuration. This multiprobe approach indicates that the electrolyte degradation process observed in the case of full Li-ion cells exhibits many similarities to what has been observed in the case of half-cells in previous works, in particular during the early stages of the cycling. Like in the case of Si/Li half-cells, the development of the inorganic part of the SEI mostly occurs during the early stage of cycling while an incessant degradation of the organic solvents of the electrolyte occurs upon cycling. However, for extended cycling, all the lithium available for cycling is consumed because of parasitic reactions and is either trapped in an intermediate part of the SEI or in the electrolyte. This nevertheless does not prevent the further degradation of the organic electrolyte solvents, leading to the formation of lithium-free organic degradation products at the extreme surface of the SEI. At this point, without any available lithium left, the cell cannot function properly anymore. Cycled positive and negative electrodes do not show any sign of particles disconnection or clogging of their porosity by electrolyte degradation products and can still function in half-cell configuration. The failure mechanism for full Li-ion cells appears then very different from that known for half-cells and is clearly due to a lack of cyclable lithium because of parasitic reactions occurring before the accumulation of electrolyte degradation products clogs the porosity of the composite electrode or disconnects the active material particles. [ABSTRACT FROM AUTHOR]

Highlights: [•] We modelled critical source areas of N and P loss at critical source areas and catchment scales. [•] Mitigation N loss from critical source areas was achieved as more grassland was incorporated into the catchment. [•] Mitigation P losses occurred by decreasing erosion and P solubility. [•] Mitigating P loss from critical source areas was 6–7 times more cost-effective than catchment-wide strategies. [•] We recommend managing critical source areas to improve water quality and minimise the impact on farm profitability. [ABSTRACT FROM AUTHOR]

Abstract: Among possible mitigation options to reduce agricultural-borne nitrate fluxes to water bodies, introduction of catch crop before spring crops is acknowledged as a cost-efficient solution at the plot scale, but it was rarely assessed at the catchment level. This study aims to evaluate a set of catch crop implantation scenarios and their consequences in a coastal catchment prone to eutrophication. The objectives are (i) to discuss the potential benefits of catch crop introduction taking into account the limitations due to the physiographic and agricultural context of the area (ii) to propose a multicriteria classification of these scenarios as a basis for discussion with stakeholders. We used the distributed agro-hydrological model TNT2 to simulate 25 scenarios of catch crop management, differing in length of catch crop growing period, place in the crop rotation and residue management. The scenarios were classified considering the variations in main crop yields and either nitrogen fluxes in stream or the global nitrogen mass balance at the catchment level. The simulations showed that in the catchment studied, little improvement can be expected from increasing the catch crop surface. Catch crop cultivation was always beneficial to reduce nitrogen losses, but led to adverse effects on main crop yields in some cases. Among the scenarios involving additional catch crop surface, introducing catch crop between two winter cereals appeared as the most promising. The classification of scenarios depended on the chosen criteria: when considering only the reduction of nitrogen fluxes in streams, exporting catch crop residues was the most efficient while when considering the global nitrogen mass balance, soil incorporation of catch crop residues was the most beneficial. This work highlights the interest, while using integrated models, of assessing simulated scenarios with multicriteria approach to provide stakeholder with a picture as complete as possible of the consequences of prospective policies. [Copyright &y& Elsevier]

Abstract: Experimental electron energy-loss spectra are presented for FePO4, LiFePO4 and NaFePO4 from 0 to 80eV. With the help of the NaFePO4 spectrum in the 50–80eV range, the double peak observed in LiFePO4 could be ascribed to the presence of FeII and not to the Li K edge, contrary to what was thought previously. Crystal field multiplet calculations confirm this attribution. Using VASP programme based on density functional theory, dielectric response calculations including local field effects in the Hartree approximation are then proven to properly simulate the fine structures due to the lithium K edge. By comparing absolute spectrum intensities, it is shown that the lithium K edge cannot be used to quantify lithium in such compounds. This detailed comparison between theoretical calculations and experimental spectra helps defining the relevant parameters governing intensities in the 50–80 energy range. [Copyright &y& Elsevier]

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]

This article reviews recent publications and takes stock of the current situation in the treatment of myeloma. [ABSTRACT FROM AUTHOR]

The current standard conditioning regimen before auto-SCT in patients with multiple myeloma is melphalan 200 mg/m2. Several attempts have recently been made to improve this aspect of the high-dose therapy procedure. The scope of this review article is to summarize current knowledge on conditioning regimens in this setting. [ABSTRACT FROM AUTHOR]

Le traitement du myélome multiple a considérablement changé dans la dernière décennie, avec un allongement très important de la survie des patients, dans toutes les tranches d’âge, grâce à l’utilisation de nouveaux agents thérapeutiques. Cette revue résume les études cliniques montrant l’intérêt de ces nouveaux médicaments, comme les immunomodulateurs ou lmids, thalidomide lénalidomide et pomalidomide, les inhibiteurs du protéasome, bortezomib et carfilzomib, et comme un agent redécouvert récemment, la bendamustine, utilisés seuls ou en association à la chimiothérapie conventionnelle, en première ligne ou en rechute. [ABSTRACT FROM AUTHOR]

The dynamic behaviour of three hydrophilic probes (two dyes and one fluorescently-labelled protein) inserted in the water layers of lyotropic lamellar phases has been studied by confocal fluorescence recovery experiments. Two different, ionic (AOT/NaCl/ H2O and non-ionic ( C12E5 /hexanol/ H2O host systems were studied. The confinement effect has been carefully monitored using the swelling properties of the lamellar phases. In all cases, we measure the evolution of the probe diffusion coefficient in the layer plane D ⊥ versus the separation between the membranes dw. Depending on the composition of the lamellar phase, this distance can be continuously adjusted from 500Å to about 20Å. For all systems, we observe a first regime, called dilute regime, where the diffusion coefficient decreases almost linearly with 1/ d w . In this regime, the Faxén theory for the friction coefficient of a spherical particle symmetrically dragged between two rigid walls can largely explain our results. More unexpectedly, when the membranes are non-ionic, and also quite flexible ( C12E5 /hexanol in water), we observe the existence of a second, concentrated (or confined) regime, where the diffusion coefficient is nearly constant and different from zero for membrane separations smaller than the particle size. This new regime can be heuristically explained by simple arguments taking into account the membrane fluidity. [ABSTRACT FROM AUTHOR]

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]

Abstract: Nanosized silicon particles were obtained by reaction between SiBr4 solution and Mg granules during a ball-milling process. X-ray diffraction measurements show that crystallized silicon was obtained after 20 h of milling, together with MgBr2, non-reacted Mg and probably SiO x . The powder was subjected to a suitable cleaning treatment in order to minimize the proportion of residual products. The different analyses carried out after the treatment showed that the obtained silicon powder consists of nanosized Si particles with a limited oxidized fraction in regard to its high surface area. This material was considered for its application as the negative electrode for lithium-ion batteries. It delivers a large initial reversible capacity (1375 mAh g−1). The capacity turns out to be almost stable after the fifth cycle, reaching around 900 mAh g−1, which is approximately twice that obtained with an electrode made from commercial 100 nm Si particles. [Copyright &y& Elsevier]

Abstract: Electron energy loss spectroscopy has been used to investigate the average oxidation state of Cr in both electrochemically and chemically delithiathed Li5/3−x Ti7/3CrO7. The O K edge, Ti L2,3 and Cr L2,3 edge were monitored. Upon removal of Li ions, the oxygen K edge shows a continuous change while the Cr L edges remain almost unchanged. The Cr 2p multiplet was compared with reference samples (Cr2O3, CrO2 and K2Cr2O7) in order to assess on the sensitivity of the Cr L-edge to the oxidation state of chromium ion. The similarity between the Cr L spectra of Cr2O3 and CrO2 makes the valence analysis difficult in Li5/3−x Ti7/3CrO7 but the presence of CrVI is excluded in oxidized samples. However, evolution of the low energy loss spectra observed in the 10–15eV region confirms the modification of the electronic structure and partial oxidation of CrIII to CrIV. [Copyright &y& Elsevier]

Abstract: The transformation of ethylbenzene (EB) was carried out on intimate mixtures of Pt/Al2O3 (PtA) and HEUO (Si/Al=15) catalysts with different composition under the following conditions: fixed bed reactor, temperature 683K, pressure of hydrogen and ethylbenzene equal to 8 and 2bar respectively, weight hourly space velocity between 5 and 60. Products result from the following transformations of ethylbenzene or/and of the reaction products: the bifunctional desired isomerization of EB into xylenes (X), the acidic reactions of disproportionation, dealkylation of EB (followed by ethylene hydrogenation) and EB–X transalkylation, the hydrogenation of EB followed by ethylcyclohexane isomerization and cracking. The selectivity to isomers, which is very low on the fresh catalysts, increases significantly during an initial period of fast deactivation, essentially at the expense of disproportionation and dealkylation by products. This deactivation as well as the increase in the selectivities to isomers were shown to result from the blockage by carbonaceous deposits of the access to the inner sites of the EUO micropores. The selectivity to isomers of EB transformation over these inner sites is very low, which could be due to the trapping of ethylcyclohexene intermediates within the monodimensional channels of EUO zeolite. In contrast, over the stabilized catalysts for which only the protonic sites of large side pockets located on the outer surface can be active, the selectivity to isomers is very high, which could be related to the environment of these sites as well as to their easy access by cycloalkene intermediates. [Copyright &y& Elsevier]

Abstract: Energy loss spectroscopic profiling is a way to acquire, in parallel, spectroscopic information across a linear feature of interest, using a Gatan imaging filter (GIF) fitted to a transmission electron microscope (TEM). This technique is capable of translating the high spatial resolution of a bright field image into a sampling of the spectral information with similar resolution. Here we evaluate the contributions of chromatic aberration and the various acquisition parameters to the spatial sampling resolution of the spectral information, and show that this can reach 0.5nm, in a system not ordinarily capable of forming electron probes smaller than 2nm. We use this high spatial sampling resolution to study the plasmon energy variation across amorphous carbon superlattices, in order to extract information about their structure and electronic properties. By modelling the interaction of the relativistic incident electrons with a dielectric layer sandwiched between outer layers, we show that, due to the screening of the interfaces and at increased collection angles, the plasmon energy in the sandwiched layer can still be identified for layer thicknesses down to 5Å. This allows us to measure the change in the well bandgap as a function of well width and to interpret it in terms of the changes in the sp2-fractions due to the deposition method, as measured from the carbon K-edges, and in terms of quantum confinement of the well wavefunction by the adjacent barriers. [Copyright &y& Elsevier]

There is a growing consensus that materials become stronger in small volumes and in the presence of large strain gradients. It has not been clear whether this is due to increased resistance to the motion of dislocations, fewer dislocations, or increased difficulty of multiplying dislocations in these situations. A classic experiment by Stölken and Evans (J.S. Stölken and A.G. Evans, Acta metall. 46 5109 (1998)) showed that thin nickel foils under bending display increased strengthening at large plastic strain values and, correspondingly, large plastic strain gradients. We have adapted their technique to small strains, and report preliminary data for the stress–strain curves of thin nickel foils through the elastic–plastic transition. These data show unambiguously that the yield strength is greater in the thinner foils. The strengthening is additive to the Hall–Petch effect, and is consistent with a size effect at the onset of plastic deformation. [ABSTRACT FROM AUTHOR]

Abstract syntax trees are a very common data-structure in language related tools. For example, compilers, interpreters, documentation generators and syntax-directed editors use them extensively to extract, transform, store and produce information that is key to their functionality. The authors present a Java back-end for ApiGen a tool that generates implementations of abstract syntax trees. The generated code is characterised by strong typing combined with a generic interface and maximal sub-term sharing for memory efficiency and fast equality checking. The goal of this tool is to obtain safe and more efficient programming interfaces for abstract syntax trees. The contribution of this work is the combination of generating a strongly typed data-structure with maximal sub-term sharing in Java. Practical experience shows that this approach is beneficial for extremely large as well as smaller data types. [ABSTRACT FROM AUTHOR]

We collected and mapped epigeous fruitbodies of both ectomycorrhizal (ECM) and saprobic fungi in an old-growth Quercus ilex L. Mediterranean forest within a permanent transect of 6400 m2 over three consecutive fruiting seasons. Out of 5382 fruitbodies, a total of 234 species were found, including 166 and 68 ECM and saprobic taxa, respectively. Both communities were mainly composed of rare species. Two genera, Russula and Cortinarius, accounted for 34.4% of ECM fruitbodies and 50% of species diversity. The three most abundant ECM species were Laccaria laccata (Scop.: Fr.) Berk. & Broome, Inocybe tigrina R. Heim, and Lactarius chrysorrheus Fr. The fruiting ECM community encompassed a few Mediterranean species and numerous broad host range temperate species. We also analysed the fruiting patterns in relation to forest structure, host composition, and natural canopy gaps. The results showed (i) a significant correlation of species richness to tree density, (ii) a richness decrease as the number of vegetation layers increases, and (iii) a preferential fruiting of some species near Q. ilex or Arbutus unedo L. Another noteworthy feature was that richness and production were greatly enhanced in canopy gaps. Selective fruiting was also observed among species. These results highlight the importance of forest structure and large woody debris for fungal conservation. [ABSTRACT FROM AUTHOR]

The epicondylar axis is a reliable reference to check the rotation of the femoral implant in total knee prostheses (TKPs). However, during the operation it seems easier to use the posterior condylar axis as a landmark. The angle between these two axes is called the posterior condylar angle (PCA). The aim of this study was to measure the PCA in arthritic knees to assess the reliability of the posterior condylar axis as a reference for the control of the rotation of the femoral implant and to look for correlation with other radiological measurements. This prospective study consisted of 103 arthritic knees (81 varus, 22 valgus) before a TKP had been done in 103 patients (75 women, 28 men). The assessment of the PCA was made by computed tomographic scanning (CT). The HKA, HKS and HKT angles were measured on the pangonogram. The posterior condylar axis was internally rotated with respect to the epicondylar axis. The average value for all the patients was 2.65° degrees with a range from 0° to 7°. The PCA was significantly increased in the valgus knees. There was no correlation between the angles on the pangonogram and the posterior condylar axis. While the preoperative assessment of the PCA by CT scanning is reliable, the results obtained indicate the marked variability in its value. If one wishes to use the posterior condylar axis as a guide for rotation, it is therefore necessary to assess the PCA for each patient using adjustable jigs according to the value obtained. No measurement on standard radiographs allowed an extrapolation of the value of the PCA, and CT scanning seems to be the preferable radiological examination. [ABSTRACT FROM AUTHOR]

Electron energy loss spectra have been recorded from BN filaments for energy losses between 2 and 50 eV.They compare well with other BN shapes (nanotubes, sheets, etc). The interpretation of all the peaks in the spectra has been made via an ab initio calculation using the FLAPW code WIEN97 (A full potential linearized augmened plane wave package for calculating crystal properties, Karlheinz Schwarz, Techn. Universita¨t Wien, Austria, 1999. ISBN 3-9501031-0-4). In order to fully simulate the observed spectra, the geometry particular to the EELS experiment has been taken into account making use of Wessjohann's relativistic formula for thin anisotropic slabs (Phys. Stat. Sol. B 77 (1976) 535). Furthermore, the effect of the convergent beam has been introduced into the simulation and has been proven to be an important parameter in obtaining the corresponding peak intensities. [Copyright &y& Elsevier]

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]

Twenty-seven patients with advanced multiple myeloma received high-dose therapy with 220 mg/m2 i.v. melphalan (HDM220) followed by autologous stem cell transplantation. At the time of HDM220, nine patients had primary refractory disease and 18 were in relapse after having responded to prior high-dose therapy. No toxic deaths were observed. The major adverse side-effect was grade 4 mucositis in 63% of patients. Two patients experienced reversible paroxysmal atrial fibrillation after HDM220. For the whole group of patients, the actuarial 3-year overall survival (OS) and event-free survival (EFS) are 36.1 and 16.9%, respectively. The probability of OS and EFS was significantly lower in patients treated for refractory relapse (22.9 and 0% at 2 years, respectively) as compared to primary refractory patients (66.7 and 64.3% at 2 years, respectively) or patients treated for chemosensitive relapse (42.9% at 2 years) (P = 0.0001). Low β2-microglobulin and CRP levels at the time of HDM220 were associated with a better OS and EFS. Our data suggest that HDM220 followed by ASCT should be considered in patients with primary refractory disease or chemosensitive disease relapsing after prior intensive therapy. [ABSTRACT FROM AUTHOR]

Studies the in-plane structure of lamellar tantalum disulfide mercury intercalated compounds. Use of transmission electron microscopy; Crystal structures containing chainlike or hexagonal close Hg arrangement containing short Hg-Hg distances; Strong resemblance to the (101 ) lattice planes in solid state beta-Hg and the hexagonal Hg layers in Hg3MF6 (M = Ta, Nb) respectively.

The aim of the present trial was to investigate the feasibility of high-dose therapy followed by autologous peripheral blood stem cell transplantation (PBSCT) as a component of front-line treatment in patients with disseminated intermediate- and high-grade non-Hodgkin's lymphoma (NHL) aged 61-65 years. From October 1993 to June 1996, 14 consecutive patients entered this singlecenter prospective pilot trial. Patients were five males and nine females, median age 63 (range 61-65). The first-line treatment consisted of three courses of CHOP therapy. Patients achieving either a partial response (PR) or a complete response (CR) after initial therapy were eligible for PBSCT, while those with refractory or progressive disease were not autografted but included in the feasibility study in an intent-to-treat analysis. Of the 14 patients, 11 achieved either a CR (one) or a PR (10) after three courses of CHOP while the three patients with no response were not autografted and subsequently died of progressive disease. PBSC collection was feasible in responding patients after G-CSF priming (10/μg/kg/day for 6 days). Conditioning therapy was the BEAM protocol. All patients engrafted after PBSCT. The median time to granulocyte (>0.5 x 10[sup9]A) and platelet recovery (>25 x 10[sup9]/1) was 12 (range 9-18) and 13 days (range 7-22), respectively. No toxic deaths VOD or IP were observed. Four of the 11 responding patients relapsed 2, 7, 9 and 12 months after PBSCT, respectively, and all died from progressive disease. Overall, 7/14 patients are alive and free from disease, 16-43 months after initial diagnosis (median 28). The actuarial overall survival is 45.7 %, and the actuarial event-free... [ABSTRACT FROM AUTHOR]

This retrospective study was undertaken to evaluate cure rates, toxicity and late effects of early intensive therapy followed by autologous stem cell transplantation (ASCT) in patients with advanced Hodgkin's disease (HD). One hundred and fifty-eight cases of ASCT registered in the French database (SFGM) were retrospectively analyzed. Disease status at the time of ASCT was first partial response (PR) in 85, first complete remission (CR1) in 45 or primary refractory in 28 cases. The median time interval between diagnosis and ASCT was 7 months (range 4-13). At the time of analysis in December 1995, 121/158 patients (76.6%) were alive, including 111 (70.2%) in continuous CR with a median follow-up for surviving patients of 46 months (range 8123). Peri-ASCT toxic death rate was 3%, and the actuarial risk of new malignancies was 4.9% at 5 years. The cumulative probability of 5-year overall survival (OS) was 75.2% for the entire group of patients, 80.6% for the chemosensitive ones, and 33.9% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The cumulative probability of 5-year event-free survival (EFS) was 66.1% for the entire group of patients, 73.7 % for the chemosensitive ones, and 26.1% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The only significant prognostic factor for both OS and EFS was disease status at the time of ASCT. Early ASCT in advanced HD is feasible, with a low risk of toxicity and without a higher rate of late effects com... [ABSTRACT FROM AUTHOR]

An original optimization strategy for creep forming is carried out by finite element thermodependent viscoplastic models. For reference design glass products, an optimum forming database is developed in two steps: the first step analyses feasibility, with elastic and viscoplastic finite element models, with regard to initial manufacture choices. With thermodependent viscoplastic finite element models, the second step leads to optimum forming parameters, concerning skeleton bending radii and/or non-homogeneous heating adjustments. [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.

We design near-autonomous microfluidic devices for concentrating aqueous solutions steadily over days in a very controlled manner. We combine suction pumps that drive the solution and concentrate it steadily, with a nanoliter-sized storage pool where the solute accumulates. The fine balance between advection and diffusion in the pump and diffusion alone in the accumulation pool yields several filling regimes. One of them is universal as being steady and independent of the solute itself. It results a specific equivalence between time and concentration, which we use to build the phase quantitative diagram of a ternary aqueous solution on nanoliter scale. [ABSTRACT FROM AUTHOR]

Experimental valence electron energy-loss spectra, obtained on different phases of LixFePO4, are analyzed with first principles calculations based on density functional theory. In the 4–7 eV range, a large peak is identified in the FePO4 spectrum but is absent in LiFePO4, which allows the easy formation of energy filtered images. The intensity of this peak, nonsensitive to the precise orientation of the crystal, is large enough to rapidly determine existing phases in the sample and permit future dynamical studies. [ABSTRACT FROM AUTHOR]

• 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]