Optimal estimation of one parameter quantum channels

We explore the task of optimal quantum channel identification, and in particular the estimation of a general one parameter quantum process. We derive new characterizations of optimality and apply the results to several examples including the qubit depolarizing channel and the harmonic oscillator damping channel. We also discuss the geometry of the problem and illustrate the usefulness of using entanglement in process estimation.Comment: 23 pages, 4 figures. Published versio

Deletion of chromosomal region 8p21 confers resistance to Bortezomib and is associated with upregulated Decoy trail receptor expression in patients with multiple myeloma

Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21)

A REVIEW ON THE BIOMEDICAL APPLICATIONS OF ALUMINA

This review presents the composition, structure, mechanical characteristics, and applications of alumina (aluminum oxide) in biomedical. Alumina used for implant manufacturing is either single-crystal sapphires or high density and quality polycrystalline. The major sources of highly-purity alumina are organic corundum and bauxite. Like any other brittle component, polycrystalline alumina's mechanical characteristics are largely dependent on grain size and porosity distribution. It was shown that, due to slowed subcritical crack production, the fatigue intensity of alumina could be increased above the crucial pressure due to the presence of liquid. Due to its high inertness, that results in outstanding biocompatibility and tissue nonsensitization, alumina has significant benefits over other products in biomedical uses. Just like in artificially joints and teeth, the higher compressive strength than tensile strength allows it more efficient for compressive loadings. There were some attempts for coating alumina on steel substrates in order to benefit of its outstanding biocompatibility and to resist metal oxidation

Chimeric Antigen Receptor T-Cell Therapy For Multiple Myeloma: A Consensus Statement From The European Myeloma Network

Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strategy has been approved in relapsed/refractory MM, it will become one of the most important indications for this therapy in Europe and world-wide. This manuscript proposes practical considerations for the use of CAR-T cell therapy in MM, and discusses several important issues for its future development

Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network

Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strateg

Daratumumab plus lenalidomide and dexamethasone for untreated Myeloma

BACKGROUND: Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.METHODS: We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival.RESULTS: At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P&lt;0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P&lt;0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells) (P&lt;0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%). CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.).</p

Validation of Half-Reaction Volumes of the Promega PowerPlex® Forensic Amplification Kits (PowerPlex® 18D Systems, PowerPlex ® 21System, PowerPlex® Fusion System and PowerPlex® Y23 System) in STR Analysis

DNA amplification is known to be the most expensive step during forensic DNA analysis. This study evaluated the half-reaction amplification protocol (12.5 µL PCR product) using DNA amplification kits from Promega PowerPlex® (PowerPlex® 18D System, PowerPlex ®21System, PowerPlex® Fusion System and PowerPlex® Y23 System), which might aid in reducing sample analysis cost by half and allow the analysis of more samples. A sensitivity study (15 samples) along with testing of various blood stain samples (n=100) that were submitted to the Medico-Legal Directorate laboratory for DNA testing was accomplished to compare the DNA profiles resulting from half-reaction volume procedure to those with full-reaction volume procedure, using three differed methods along with standard protocol to evaluate the effect of half reaction volume with some variables. Results demonstrated the use of half-reaction amplification protocol preceded by washing step for all aforementioned DNA amplification kits gave a robust and reliable amplification result that aid to increase the number of samples analyzed and decreased the test cost for each kit without compromising the quality of 3DNA profiles obtained

Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial

© 2017 The Authors. Published by Nature Publishing Group. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/leu.2017.111© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ≥ very good partial response (VGPR; n=679), ≥ partial response (PR; n=1 225) or ≤ stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ≥ VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ≥ VGPR and ≥ PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ≥ VGPR and ≥ PR, respectively. In patients with CR, ≥ VGPR or ≥ PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.Published versio

Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group

This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes

Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10-8), 6q21 (rs9372120, P=9.09 × 10-15), 7q36.1 (rs7781265, P=9.71 × 10-9), 8q24.21 (rs1948915, P=4.20 × 10-11), 9p21.3 (rs2811710, P=1.72 × 10-13), 10p12.1 (rs2790457, P=1.77 × 10-8), 16q23.1 (rs7193541, P=5.00 × 10-12) and 20q13.13 (rs6066835, P=1.36 × 10-13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development