European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy

On 21 November 2016, the European Commission issued a marketing authorisation valid throughout the European Union for ixazomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Ixazomib was evaluated in one, randomised, double-blind, phase III study comparing ixazomib plus lenalidomide and dexamethasone (n=360; ixazomib arm) versus placebo plus lenalidomide and dexamethasone (n=362; placebo arm) in adult patients with relapsed and/or refractory multiple myeloma who had received at least one prior therapy. The median progression-free survival (PFS) in the intent-to-treat population was 20.6 months in patients treated with ixazomib compared with 14.7 months for patients in the placebo arm (stratified HR=0.742, 95% CI 0.587 to 0.939, stratified p-value=0.012). The most frequently reported adverse reactions (≥20%) within the ixazomib and placebo arms were diarrhoea (42% vs 36%), constipation (34% vs 25%), thrombocytopaenia (28% vs 14%), peripheral neuropathy (28% vs 21%), nausea (26% vs 21%), peripheral oedema (25% vs 18%), vomiting (22% vs 11%) and back pain (21% vs 16%). The scientific review concluded that the gain in PFS of 5.9 months observed with ixazomib was considered clinically meaningful. Concerning the possible uncertainty about the magnitude of the effect, this uncertainty was acceptable given the favourable toxicity profile, and considering that ixazomib is the first agent to allow oral triple combination therapy in this patient population which represents a therapeutic innovation in terms of convenience for patients. Therefore, the benefit-risk for ixazomib in combination with lenalidomide and dexamethasone was considered positive, although the efficacy evidence was not as comprehensive as normally required

Evaluating a Prioritization Framework for Monitoring Chemicals of Emerging Concern in the Salish Sea Based on Lessons Learned from Western States Programs

We are now approaching a tipping point where priority pollutants may no longer be the primary driver of environmental impairment. Contaminants of Emerging Concern (CECs) present a challenge to environmental monitoring and management programs because the rapidly emerging state of the knowledge requires an adaptive and transparent prioritization framework. The state of the science, treatment technologies, and regulatory policies are not well understood, CEC quantification is challenging and expensive, and the management approach is not simply a concentration based criteria, but may include biological end-points. The need for a shared responsibility and leveraging across many programs was evaluated through a series of webinars with other programs studying CECs including Columbia River Toxics Program, Washington Department of Ecology, Oregon Department of Environmental Quality, Southern California Coastal Waters Research Project, and San Francisco Bay Regional Monitoring Program. The lessons learned were articulated into a 10-step prioritization framework. The critical lesson learned included: 1) Develop clear objectives, definitions of CECs, and target audience; 2) Identify conceptual models to provide a clear target for the appropriate media to monitor for various chemicals and at what frequency; 3) Define the chemical characteristics in terms of usage, persistence, bioaccumulation, and toxicity; 4) Develop a target CEC analyte list; 5) Screen and rank the CEC analyte list based on chemical characteristics, environmental concentrations, and state of the science; 6) Create a transparent prioritization process to include input from key stakeholders and end users that builds consensus during development; 7) Prioritize the chemical categories by using specific metrics such as available data, status of analytical methods, available thresholds, costs, programmatic concerns and opportunities for leveraging with other programs; 8) Identify potential biological end-points and other indicators; 9) Create a formal review process to support data and knowledge sharing, adaptively manage prioritization to include new science and critical research gaps; and 10) Develop a working group to facilitate leveraging of funds across many programs

Cryogenic time-domain multiplexer based on SQUID arrays and superconducting/normal conducting switches

EUCAS2013 Volume: 507 Host publication title: 11th European Conference on Applied Superconductivity (EUCAS2013)We have demonstrated the operation of a 12-channel Beyer-style SQUID-based time domain multiplexer. It was manufactured using a fabrication process that is cross-compatible between VTT and IPHT-Jena. The multiplexer consists of twelve 12-SQUID series arrays, each shunted by a Zappe-style interferometer array acting as a flux-controlled superconducting/normal conducting switch. By keeping all switches but one in the superconducting state, it is possible to select one active readout channel at a time. A flux feedback coil common to all SQUID arrays allows realization of a flux-locked loop. We present characteristics of the multiplexer and measurement data from experiments with a 25-pixel X-ray calorimeter array operated at T <100 mK in a dilution refrigerator.Peer reviewe

Decoupling of a Current-Biased Intrinsic Josephson Junction from its Environment

We have observed a dissipative phase diffusion branch in arrays of hysteretic high-Tc intrinsic Josephson junctions. By comparing the data with a thermal activation model we extract the impedance seen by the junction in which phase diffusion is occurring. At the plasma frequency this junction is isolated from its environment and it sees its own large (~ kilo Ohm) impedance. Our results suggest that stacks of Josephson junctions may be used for isolation purposes in the development of a solid state quantum computer

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon

We report the first measurement of coherent elastic neutrino-nucleus scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer \cevns over the background-only null hypothesis with greater than $3\sigma$ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2 $\pm$ 0.7) $\times$10$^{-39}$ cm$^2$ -- consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the \cevns process and provides improved constraints on non-standard neutrino interactions.Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3: fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6: fix Eq 1, new fig 3, V7 final version, updated with final revision

Precision Measurement of the Proton and Deuteron Spin Structure Functions g2 and Asymmetries A2

We have measured the spin structure functions g2p and g2d and the virtual photon asymmetries A2p and A2d over the kinematic range 0.02 < x < 0.8 and 0.7 < Q^2 < 20 GeV^2 by scattering 29.1 and 32.3 GeV longitudinally polarized electrons from transversely polarized NH3 and 6LiD targets. Our measured g2 approximately follows the twist-2 Wandzura-Wilczek calculation. The twist-3 reduced matrix elements d2p and d2n are less than two standard deviations from zero. The data are inconsistent with the Burkhardt-Cottingham sum rule if there is no pathological behavior as x->0. The Efremov-Leader-Teryaev integral is consistent with zero within our measured kinematic range. The absolute value of A2 is significantly smaller than the sqrt[R(1+A1)/2] limit.Comment: 12 pages, 4 figures, 2 table

Measurement of the Proton and Deuteron Spin Structure Functions g2 and Asymmetry A2

We have measured the spin structure functions g2p and g2d and the virtual photon asymmetries A2p and A2d over the kinematic range 0.02 < x < 0.8 and 1.0 < Q^2 < 30(GeV/c)^2 by scattering 38.8 GeV longitudinally polarized electrons from transversely polarized NH3 and 6LiD targets.The absolute value of A2 is significantly smaller than the sqrt{R} positivity limit over the measured range, while g2 is consistent with the twist-2 Wandzura-Wilczek calculation. We obtain results for the twist-3 reduced matrix elements d2p, d2d and d2n. The Burkhardt-Cottingham sum rule integral - int(g2(x)dx) is reported for the range 0.02 < x < 0.8.Comment: 12 pages, 4 figures, 1 tabl

Editorial Board

Source at http://dx.doi.org/10.1186/s12888-017-1345-8 Background: The duration of untreated psychosis is determined by both patient and service related factors. Few studies have considered the geographical accessibility of services in relation to treatment delay in early psychosis. To address this, we investigated whether treatment delay is co-determined by straight-line distance to hospital based specialist services in a mainly rural mental health context. Methods: A naturalistic cross-sectional study was conducted among a sample of recent onset psychosis patients in northern Norway (n = 62). Data on patient and service related determinants were analysed. Results: Half of the cohort had a treatment delay longer than 4.5 months. In a binary logistic regression model, straight-line distance was found to make an independent contribution to delay in which we controlled for other known risk factors. Conclusions: The determinants of treatment delay are complex. This study adds to previous studies on treatment delay by showing that the spatial location of services also makes an independent contribution. In addition, it may be that insidious onset is a more important factor in treatment delay in remote areas, as the logistical implications of specialist referral are much greater than for urban dwellers. The threshold for making a diagnosis in a remote location may therefore be higher. Strategies to reduce the duration of untreated psychosis in rural areas would benefit from improving appropriate referral by crisis services, and the detection of insidious onset of psychosis in community based specialist services

CD34+ cell mobilization, blood graft composition, and posttransplant recovery in myeloma patients compared to non‐Hodgkinʼs lymphoma patients: results of the prospective multicenter GOA study

BACKGROUNDAutologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non‐Hodgkinʼs lymphoma (NHL).STUDY DESIGN AND METHODSIn this prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome.RESULTSMultiple myeloma patients mobilized CD34+ cells more effectively (6.3 × 106/kg vs. 3.9 × 106/kg, p = 0.001). The proportion of poor mobilizers (peak blood CD34+ cell count 100 days) nonrelapse mortality (NRM; 6% vs. 0%, p = 0.003).CONCLUSIONSNon‐Hodgkinʼs lymphoma and MM patients differ in terms of mobilization of CD34+ cells, graft cellular composition, and posttransplant recovery. Thus, the optimal graft characteristics may also be different.</p

Possible robust insulator-superconductor transition on solid inert gas and other substrates

We present observations of the insulator-superconductor transition in ultrathin films of Bi on amorphous quartz, quartz coated with Ge, and for the first time, solid xenon condensed on quartz. The relative permeability $\epsilon_r$ ranges from 1.5 for Xe to 15 for Ge. Though we find screening effects as expected, the I-S transition is robust, and unmodified by the substrate. The resistance separatrix is found to be close to h/4e^2 and the crossover thickness close to $\rm 25 \AA$ for all substrates. I-V studies and Aslamazov-Larkin analyses indicate superconductivity is inhomogeneous. The transition can be understood in terms of a percolation model.Comment: accepted in Physical Review